Dementia revisited "Total costs of care for people
with Dementia could top $1.1 trillion in 2050
"
[in the U.S. only, and 2018 dollars] [98-99.1]

--- Alzheimer's Association


By 2050 Dementia is expected to occur every 33 seconds in the U.S. which is almost double the present rate (hence, worldwide it would amount to having a new case nearly every second!) [11-11.3].

Percentage-wise, one of every four persons alive today will, eventually, end up with dementia [89-89.2]. In the foreseeable future, though, it will amount to every second person having to live with this faith; while society's future ability to take adequate care of this portion of the population is questionable at best [109].

It's prudent, therefore, to step back and review the efforts to concur dementia from its historical perspective and its current developments.

Dr. Alois Alzheimer declared in 1906 that 'plaques' and 'tangles', found in the brain, are the hallmarks that cause the disease which is bearing his name (widely accepted and known as the 'amyloid hypothesis') yet, lately seriously questioned of it being the cause of this disorder [1-8.11].

Well into the second century since then, despite a continuous extensive and well-supported [108]. research on these elements, Alzheimer's disease, and dementia in general, still can't be cured, prevented, or even slowed down [9-10.1].

The trust of work to bring Alzheimer's disease under control, since the inception of the 'amyloid hypothesis' to date, centered by and large, on treating the affliction as a disease in need of a cure [103-105]. All the efforts to find this elusive cure have failed with no exception [106-107].

This begs examination of the question:

can the onset of dementia be prevented in the first place?

The following information appears to have significant implications for the fight for conquering the dementia plague. It's thought to be of interest as it promises a potential breakthrough.

Ample supporting data already available from a good number of independent studies suggests that cerebral hypo-perfusion, at any age, is associated with [93-96.18] and is the possible root cause of Alzheimer's disease and dementia [12-22.49], at a later age [32.2-38.2].

However, it's incumbent on the research sphere to generate the required experimental data and to provide a direct study proof of this condition's prevalence in the general population of all ages [100-100.1].

The proposed study should comprise subjects of all age groups [90-90.4]. A certain percentage in each of these groups is likely to show brain blood flow which is, usually, expected in dementia cases regardless of the subject's age or health condition [29-29.1]. The overall percentage of low brain blood flow subjects of all groups would, eventually, agree with the percentage of dementia cases in the general population; which will come to serve as a strong indication that these subjects may end up with some form of dementia at a later age unless promptly treated for the condition [30-30.1].

Once accomplished, it will potentially prompt implementation of the simple procedure outlined below, and hence, it has the potential to prevent the onset of dementia altogether.

This procedure calls for routine monitoring of blood flow to the brain [92-92.10], similar to how blood pressure is routinely tested [31-31.1]. It would allow for a timely [101] clinical/pharmacological intervention to take place [97-97.5], and correct the condition of cerebral hypo-perfusion, where it occurs [32-32.1.18].

If you are in a position to influence the undertaking of such a research project (or, otherwise, can get the word out) you are urged to take action and be part of the solution for rendering dementia history.

The following is suggested as a possible direct cause of dementia: reduced blood flow in the brain is known to result in elevated brain temperature [CCSVI]. This condition is fairly common in the elderly [25-27.2], in all likelihood, but also conceivably exists, to some degree, in all other age groups [102-102.1].

It, therefore, is liable to cause an increase in brain temperature and can result in damage to brain-cells [39-40.4]. It ought to be in particular true where the condition becomes chronic [41-84.11] and lingers on silently for years without being directly detected [24-24.5]; way before any symptoms of dementia manifest themselves [28-28.9.3].

Aristotle, allegedly, stated that: "the role of the blood in the brain is to COOL the brain". Ironically, he may have been right for a change. At least this time.

Regardless of whether you do, or don't accept it as a possible cause, would you consider routine monitoring of brain blood flow to be of any use? [91-91.3] Bearing in mind that blood pressure is not necessarily indicative of cerebral blood flow [85-88.3].

Monitoring brain blood flow can readily be accomplished nowadays. Although being even less invasive, it could be somewhat more cumbersome than blood pressure measurement [23]. However, ultimately it's bound to be just as simple as, say, taking the temperature with an electronic thermometer (and not more costly at that).


Joel Tepper, P.Eng.
Edmonton, Alberta, Canada
telejt[delete_me]@shaw.ca


=REFERENCES EXCERPTS=

i.
CCSVI, Brain Cooling and Blood Flow
Posted on September 3, 2010 by uprightdoctor

"The upper cervical spine plays an important role in the venous drainage system of the brain, brain blood flow and brain COOLING ... decreased blood flow and DECREASED COOLING capacity of the brain."
(emph. added j.t.)

-------------------------------------------

ii.
Cerebral Cooling During Increased Cerebral Blood Flow in the Monkey
ArticleinProceedings of The Society for Experimental Biology and Medicine 124(2):555-7 March 1967
DOI: 10.3181/00379727-124-31788

"... Intracerebral temperature gradients are basically dependent upon the rate of REMOVAL of heat from the brain by the arterial blood."
(emph. added j.t.)

------------------------------------------

iii.
Body and brain temperature coupling: the critical role of cerebral blood flow
By: Mingming Zhu et al.
J Comp Physiol B. 2009 Aug;179(6):701-10.
DOI: 10.1007/s00360-009-0352-6

"... LOWER cerebral blood flow promotes HIGHER deep-brain/body-core TEMPERATURE ..."
(emph. added j.t.)

------------------------------------------

iv.
Dual role of cerebral blood flow in regional brain temperature control in the healthy newborn infant
By: Sachiko Iwata et al.
Int J Dev Neurosci. 2014 Oct;37:1-7
DOI: 10.1016/j.ijdevneu.2014.05.010

"... brain PERFUSION, which REMOVES heat ..."
(emph. added j.t.)

------------------------------------------

v.
Specialized brain cooling in humans?
By: G L Brengelmann
FASEB J 1993 Sep;7(12):1148-52; discussion 1152-3
DOI: 10.1096/fasebj.7.12.8375613

"... the meshwork of arterial vessels in the carotid rete PRECOOLS blood bound for the brain ..."
(emph. added j.t.)

Back↑

------------------------------------------

vi.
Selective brain cooling
By: F Corrard
Arch Pediatr. 1999 Jan;6(1):87-92
DOI: 10.1016/S0929-693X(99)80080-3

"... the arterial blood temperature, of which CEREBRAL temperature depends upon, is reduced by the COOLED venous blood ..."
(emph. added j.t.)

------------------------------------------

vii.
Comparison of brain temperature to core temperature
J Neurosci Nurs. 2004 Feb;36(1):23-31

"... acute neurological injury ... All 15 studies found that brain TEMPERATURE was HIGHER than all measures of core temperature with mean differences of 0.39 to 2.5 degrees C reported."
(emph. added j.t.)

------------------------------------------

viii.
Selective BRAIN COOLING in humans: "fancy" or fact?
By: M Cabanac
FASEB J. 1993 Sep;7(12):1143-6; discussion 1146-7
DOI: 10.1096/fasebj.7.12.8375612

"... arterial blood flow of the brain is sufficient to COOL the brain ..."
(emph. added j.t.)

------------------------------------------

ix.
Brain temperature EXCEEDS systemic temperature in head-injured patients
By: C S Rumana et al.
Crit Care Med. 1998 Mar;26(3):562-7
DOI :10.1097/00003246-199803000-00032

"... Thirty patients with severe head injuries ...
...The difference in the brain and body temperatures INCREASED when cerebral perfusion pressure DECREASED ...
.... brain temperature INCREASE over the core body temperature ranged from 0.30 degrees to 2.1 degrees C ..."
(emph. added j.t.)

------------------------------------------

x.
The thermodynamic brain
By: Joseph Donnelly et al.
Crit Car. 2014 Dec 12;18(6):693
DOI: 10.1186/s13054-014-0693-8

"... Brain blood flow can thus be understood as A COOLER for the brain ..."
(emph. added j.t.)

Back↑

------------------------------------------

xi.
Selective brain cooling increases cortical cerebral blood flow in rats
By: J W Kuluz et al.
Am J Physiol. 1993 Sep;265(3 Pt 2):H824-7
DOI: 10.1152/ajpheart.1993.265.3.H824

"... as brain temperature INCREASED, cortical cerebral blood flow DECREASED ..."
(emph. added j.t.)

------------------------------------------

xii.
Guttural pouches, brain temperature and exercise in horses
By: Graham Mitchell et al.
Biol Lett. 2006 Sep 22;2(3):475-7
DOI: 10.1098/rsbl.2006.0469

"... We conclude that cerebral blood flow REMOVES heat from the brain ..."
(emph. added j.t.)

------------------------------------------

xiii.
Measurement of brain temperature with magnetic resonance spectroscopy in acute ischemic* stroke
By: Bartosz Karaszewski et al.
Ann Neurol. 2006 Oct;60(4):438-46
DOI: 10.1002/ana.20957

"... Temperature is ELEVATED in acutely ischemic* brain ..."

*Brain Ischemia
Cerebral ischemia is defined as a flow of blood to the brain that is
insufficient to meet its metabolic demands, leading to loss of function and CELL DEATH.
(emph. added j.t.)

------------------------------------------

xiv.
Cerebral Vascular Control and Metabolism in Heat Stress
By: Anthony R Bain et al.
Compr Physiol. 2015 Jul 1;5(3):1345-80
DOI: 10.1002/cphy.c140066

"... Any REDUCTION in cerebral blood flow ATTENUATES the brain's convective HEAT LOSS ..."
(emph. added j.t.)

------------------------------------------

xv.
Theoretical model of temperature regulation in the brain during changes in functional activity
By: Alexander L Sukstanskii et al.
Proc Natl Acad Sci U S A. 2006 Aug 8;103(32):12144-9
DOI: 10.1073/pnas.0604376103

"... [Brain] heat REMOVAL by blood flow ..."
(emph. added j.t.)

Back to: "elevated brain temperature"↑

===========================

P.S.

The following references excerpts were, subsequently, brought to my attention:

1.
The dark sides of amyloid in Alzheimer's disease pathogenesis
By: Pierpaolo Sorrentino et al.
FEBS Lett. 2014 Mar 3;588(5):641-52
DOI: 10.1016/j.febslet.2013.12.038

"Many evidences are starting to cast DOUBT on beta-amyloid as the primary causative factor in alzheimer's disease."
(emph. added j.t.)

--------------------------------------

2.
Alzheimer's disease and AMYLOID: culprit or COINCIDENCE?
By: Stephen D Skaper
Int Rev Neurobiol. 2012;102:277-316
DOI: 10.1016B978-0-12-386986-9.000119

"... amyloid beta alone is UNABLE TO ACCOUNT for all aspects of Alzheimer's Disease ... raises the question as to whether accumulation of amyloid beta peptides is indeed the culprit for neurodegeneration in Alzheimer's Disease."
(emph. added j.t.)

--------------------------------------

3.
Inconsistencies and controversies surrounding the AMYLOID HYPOTHESIS of Alzheimer's disease
By: Gary P Morris et al.
Acta Neuropathol Commun
2014 Sep 18;2:135
DOI: 10.1186/s40478-014-0135-5

"We conclude it is essential to expand our view of pathogenesis BEYOND amyloid beta and tau pathology ..."
(emph. added j.t.)

--------------------------------------

4.
On the origin of Alzheimer's disease. Trials and tribulations of the amyloid hypothesis
By: Michael A Castello et al.
Ageing Res Rev. 2014 Jan;13:10-2
DOI: 10.1016/j.arr.2013.10.001

"We believe that current evidence DOES NOT SUPPORT the amyloid cascade hypothesis for late onset Alzheimer's disease."
(emph. added j.t.)

--------------------------------------

5.
The pathophysiology of Alzheimer's disease with special reference to "amyloid cascade hypothesis"
By: Akira Tamaoka
Rinsho Byori. 2013 Nov;61(11):1060-9

"... cognitive decline in Alzheimer's disease patients IS NOT CORRELATED with the levels of senile plaque formation."
(emph. added j.t.)

Back ↑

--------------------------------------

6.
Understanding the cause of sporadic Alzheimer's disease
By: Henrik Zetterberg et al.
Expert Rev Neurother. 2014 Jun;14(6):621-30
DOI: 10.1586/14737175.2014.915740

"The AMYLOID BETA HYPOTHESIS posits that cerebral beta-amyloidosis is a critical early event in Alzheimer's disease pathogenesis. However, failed clinical trials of amyloid beta-centric drug candidates HAVE CALLED THIS HYPOTHESIS INTO QUESTION."
(emph. added j.t.)

--------------------------------------

7.
A critical analysis of the 'amyloid cascade hypothesis'
By: R A Armstrong
Folia Neuropathol. 2014;52(3):211-25

"It was concluded:
(1) beta-amyloid and tau could be the PRODUCTS rather than the cause of neurodegeneration in Alzheimer's disease,
(2) it is DOUBTFUL whether there is a direct causal link between beta-amyloid and tau, and
(3) senile plaques and neurofibrillary tangles MAY NOT BE DIRECTLY RELATED to the development of dementia ..."
(emph. added j.t.)

-------------------------------------

8.
Microvessel occlusions ALTER amyloid-beta plaque morphology in a mouse model of Alzheimer's disease
By: Yuying Zhang et al.
J Cereb Blood Flow Metab. 2020 Oct.
DOI: 10.1177/0271678X19889092

"vascular dysfunction is correlated to the incidence and severity of Alzheimer's disease."
(emph. added j.t.)

---------------------------------------

8.1
The role of chronic brain hypoperfusion in the pathogenesis of Alzheimer's disease--facts and hypotheses
By: Denes Zadori et al.
Ideggyogy Sz. 2007 Nov 30;60(11-12):428-37
PMID: 18198789

"Hypoperfusion LEADS to ... neurodegenerative process ... of this neuronal tangles and the beta-amyloid plaques ..."
(emph. added j.t.)

---------------------------------------

8.2
Endothelial dysfunction: A potential therapeutic target for geriatric depression and brain amyloid deposition in Alzheimer's disease?
By: Elsa Isingrini et al.
Curr Opin Investig Drugs. 2009 Jan;10(1):46-55
PMID: 19127486

"... strong evidence suggests that vascular diseases and vascular risk factors are associated with ... Alzheimer's disease ... COULD PARTIALLY EXPLAIN ... THE ONSET ... OF AMYLOID DEPOSITION in the brains of patients with Alzheimer's disease ..."
(emph. added j.t.)

Back ↑

---------------------------------------

8.3
Cerebral blood flow measured by arterial spin labeling MRI as a preclinical marker of Alzheimer's disease
By: Christina E Wierenga et al.
J Alzheimers Dis. 2014
DOI: 10.3233/JAD-141467

"... cerebral hypoperfusion as a useful biomarker, possibly present even EARLIER than amyloid-beta accumulation ..."
(emph. added j.t.)

---------------------------------------

8.4
Blood pressure and the risk for dementia: a double edged sword
By: Sean P Kennelly et al.
Ageing Res Rev. 2009 Apr.
DOI: 10.1016/j.arr.2008.11.001

"... ischaemic* state may LEAD TO increased cerebral BETA-AMYLOID accumulation ..."

*Brain Ischemia Cerebral ischemia is defined as a flow of blood to the brain that is insufficient to meet its metabolic demands, leading to loss of function and CELL DEATH.
(emph. added j.t.)

---------------------------------------

8.5
A possible role of atrial fibrillation as a risk factor for dementia
By: E Ettorre et al.
Arch Gerontol Geriatr. 2009;49 Suppl 1:71-6
DOI: 10.1016/j.archger.2009.09.014

"... response in patients with Alzheimer's disease to therapy that improves cerebral blood flow is a consistent finding; the same CANNOT BE SAID of antiamyloid treatments ..."
(emph. added j.t.)

---------------------------------------

8.6
Alzheimer disease as a vascular disorder: nosological evidence
By: J C de la Torre
Stroke. 2002 Apr;33(4):1152-62
DOI: 10.1161/01.str.0000014421.15948.67

"... the CAUSE of this disorder [Alzheimer disease] has remained UNCERTAIN until now ..."

"... Evidence that sporadic (nongenetic) Alzheimer disease is primarily a vascular rather than a neurodegenerative disorder ..."
(emph. added j.t.)

Back ↑

---------------------------------------

8.7
Management of cerebral small vessel disease for the diagnosis and treatment of dementia
By: Masafumi Ihara
Brain Nerve. 2013 Jul;65(7):801-9

"... The discouraging results of immunotherapy clinical trials for Alzheimer's disease have SHIFTED the scientific attention from the classical neuron-centric approach TOWARDS a novel neurovascular approach ..."
(emph. added j.t.)

---------------------------------------

8.8
Cerebral Hemodynamics in Mild Cognitive Impairment: A Systematic Review
By: Lucy Beishon et al.
J Alzheimers Dis. 2017;59(1):369-385
DOI: 10.3233/JAD-170181

"... Vascular pathology PRECEDES the deposition of amyloid ..."
(emph. added j.t.)

---------------------------------------

8.9
Alzheimer's disease: cardiovascular risk factors must be assessed
By: Antoine et al.
Rev Med Interne. 2006 Jan;27(1):21-31
DOI: 10.1016/j.revmed.2005.04.037

"The theory of a neurotoxicity initiated by amyloid deposition is questioned."

---------------------------------------

8.10
Is Alzheimer's disease a neurodegenerative or a vascular disorder? Data, dogma, and dialectics
By: Jack C de la Torre
Lancet Neurol. 2004 Mar;3(3):184-90
DOI: 10.1016/S1474-4422(04)00683-0

"... research reveals no compelling evidence that amyloid deposition is neurotoxic in human beings or that it results in neurodegenerative changes ..."

---------------------------------------

8.11
Of Energy and Entropy: The Ineluctable Impact of Aging in Old Age Dementia
By: Virginia Boccardi et al.
Int J Mol Sci. 2017 Dec 9;18(12):2672
DOI: 10.3390/ijms18122672

"... despite decades of studies [of Alzheimer's disease], the underlying mechanisms remain unresolved ..."

Back to: "lately seriously questioned of it being the cause of this disorder"↑

---------------------------------------

9.
Tibetan medicine ... treatment of Alzheimer disease
By: Jing-Ming Shi et al.
Int J Clin Exp Med. 2 015 Nov 15;8(11):19874-80
eCollection 2015

... Currently, the pathogenesis of Alzheimer Disease is still uncertain ... NO DRUG can really PREVENT AND CURE Alzheimer Disease ...
(emph. added j.t.)

--------------------------------------

10.
Computer mouse movement patterns: A potential marker of mild cognitive impairment
By: Adriana Seelye et al.
Alzheimer's & Dementia: Volume 1, Issue 4 p. 472-480
DOI: 10.1016/j.dadm.2015.09.006

... Alzheimer's disease is a leading cause of death in America and currently there is NO PREVENTION OR CURE ...
(emph. added j.t.)

--------------------------------------

10.1
Nerve Growth Factor Gene Therapy: Activation of Neuronal Responses in Alzheimer Disease
By: Mark H Tuszynski et al.
JAMA Neurol. 2015 Oct;72(10):1139-47
DOI: 10.1001/jamaneurol.2015.1807

"... Alzheimer disease .... LACKS EFFECTIVE DISEASE-MODIFYING THERAPIES ..."
(emph. added j.t.)

Back to: "dementia in general, still can't be cured, prevented, or even slowed down"↑

--------------------------------------

11.
Alzheimer's Disease and Dementia, Under-Recognized Public Health Crisis in China
By: Mi Tian, et al.
Journal of Gerontology & Geriatric Research
Jun 14, 2014; Acc date: Jul 06, 2014 Pub date: Jul 08, 2014
DOI:10.4172/2167-7182.1000162

"Worldwide, 35.6 million people were estimated to be living with dementia in 2010, with 7.7 million new cases each year; 115.4 million people are EXPECTED to have dementia in 2050 ..."
(emph. added j.t.)

--------------------------------------

11.1
Alzheimer's disease drug development: translational neuroscience strategies
By: Jeffrey L Cummings et al.
CNS Spectr. 2013 Jun;18(3):128-38.
DOI: 10.1017/S1092852913000023

"Alzheimer's disease is an URGENT public health challenge that is rapidly approaching EPIDEMIC PROPORTIONS ..."
(emph. added j.t.)

--------------------------------------

11.2
Possibilities of Dementia Prevention - It is Never Too Early to Start
By: Sandra Morovic et al.
J Med Life. 2019 Oct-Dec;12(4):332-337
DOI: 10.25122/jml-2019-0088

"... More than 50 million people worldwide suffer from dementia, and this number is PREDICTED TO TRIPLE by 2050 ..."
(emph. added j.t.)

--------------------------------------

11.3
A Neurologist's Practical Approach to Cognitive Impairment
By: Philip W Tipton et al.
Semin Neurol. 2021 Dec
DOI: 10.1055/s-0041-1726354

"... The global prevalence of dementia is EXPECTED TO TRIPLE by the year 2050 ..."
(emph. added j.t.)

Back to: "a new case nearly every second"↑

--------------------------------------

12.
Detecting perfusion deficit in Alzheimer's disease and mild cognitive impairment patients ...
By: Shaozhen Yan et al.
J Magn Reson Imaging. 2019 Apr;49(4):1099-1104
DOI: 10.1002/jmri.26283. Epub 2018 Oct 14

"... Vascular factors contributing to cerebral HYPOPERFUSION are implicated in the risk of developing Alzheimer's disease ..."
(emph. added j.t.)

--------------------------------------

12.01
Prevalence and cognitive impact of cerebrovascular findings in Alzheimer's disease: a retrospective, naturalistic study
By: N Tabet et al.
Int J Clin Pract. 2009 Feb;63(2):338-45
DOI: 10.1111/j.1742-1241.2008.01971.x

"Cerebrovascular disease is a MAJOR RISK FACTOR for cognitive decline associated with progression to ALZHEIMER'S DISEASE AND DEMENTIA ..."
(emph. added j.t.)

--------------------------------------

12.02
Leaky memories ...
By: Wenlu Li et al.
J Cereb Blood Flow Metab. 2020 Sep.
DOI: 10.1177/0271678X20938146

"... the role of VASCULAR contributions to Alzheimer's disease and dementia is increasingly recognized."
(emph. added j.t.)

--------------------------------------

12.03
Memory impairment ... is associated ... with hippocampal hypoperfusion ...
By: Abbie C Johnson et al.
J Cereb Blood Flow Metab. 2020 Apr.
DOI: 10.1177/0271678X19848510

... hippocampal PERFUSION as underlying mechanisms of memory impairment ...
(emph. added j.t.)

--------------------------------------

12.04
Two-photon microscopic imaging of capillary red blood cell flux in mouse brain reveals vulnerability of cerebral white matter to HYPOPERFUSION
By: Baoqiang Li et al.
J Cereb Blood Flow Metab. 2020 Mar.
DOI: 10.1177/0271678X19831016.

"... blood flow ... HYPOPERFUSION ... potentially exacerbating ... DETERIORATION in brain conditions ..."
(emph. added j.t.)

Back ↑

--------------------------------------

12.05
Treatment of vascular risk factors is associated with slower decline in Alzheimer disease
By: Yan Deschaintre et al.
Neurology. 2009
DOI: 10.1212/WNL.0b013e3181b59bf3

"There is growing evidence that VASCULAR RISK FACTORS contribute to cognitive decline."
(emph. added j.t.)

--------------------------------------

12.06
Cognitive impairment in heart failure: issues of measurement and etiology
By: Barbara Riegel et al.
Am J Crit Care. 2002 Nov;11(6):520-8
PMID: 12425402

"Cognitive impairment is relatively common in patients with heart failure..."

[does the cognitive impairment, actually, caused by cerebral blood flow reduction rather then directly by the heart failure per se? j.t.]

--------------------------------------

12.1
Pathophysiology of neuronal energy crisis in Alzheimer's disease
By: Jack C de la Torre
Neurodegener Dis. 2008;5(3-4):126-32
DOI: 10.1159/000113681

... preclinical detection tools for Alzheimer's disease are proof of concept that cerebral hypoperfusion is one of the earliest pathological signs in the DEVELOPMENT of cognitive failure ...
(emph. added j.t.)

--------------------------------------

12.2
... Quantitative Study of the Changes in Cerebral Blood Flow ...
By: Li Dongxue et al.
Journal of Alzheimer's Disease, vol. 68, no. 1, pp. 1-24, 2019

"... REDUCTION in [cerebral] blood perfusion in multiple regions existed during the PROGRESSION of Alzheimer's disease ..."
(emph. added j.t.)

--------------------------------------

12.3
... hypoperfused brain ... primary target for the development of Alzheimer's disease
By: Ali Aliyev et al.
J Neurol Sci. 2005 Mar 15;229-230:285-92
DOI: 10.1016/j.jns.2004.11.040

... The role of hypoperfusion, as a KEY FACTOR ... appears to be widely accepted as an INITIATOR of Alzheimer's disease ...
(emph. added j.t.)

Back ↑

--------------------------------------

12.4
Relation of neurocardiovascular instability to cognitive, emotional and functional domains
By: C Bendini et al.
Arch Gerontol Geriatr. 2007;44 Suppl 1:69-74
DOI: 10.1016/j.archger.2007.01.010

... REDUCES cerebral blood flow, INCREASING the risk of cognitive impairment ...
(emph. added j.t.)

--------------------------------------

13.
Brain hypoperfusion: a critical factor in vascular dementia
By: Gustavo C Roman
Neurol Res
2004 Jul;26(5):454-8
DOI: 10.1179/016164104225017686

"... hypoperfusion explain the HIGH RISK for the development of cognitive impairment and vascular dementia in older patients ..."
(emph. added j.t.)

--------------------------------------

14.
NEUROVASCULAR Dysfunction and Neurodegeneration in Dementia and Alzheimer's Disease
By: Amy R Nelson et al.
Biochim Biophys Acta May 2016
DOI: 10.1016/j.bbadis.2015.12.016

"vascular insults can INITIATE a cascade of molecular events leading to neurodegeneration, cognitive impairment, and dementia ..."
(emph. added j.t.)

--------------------------------------

15.
Post-mortem Assessment of Hypoperfusion of Cerebral Cortex in Alzheimer's Disease and Vascular Dementia
By: Taya Thomas et al.
2015 Apr;138(Pt 4):1059-69
DOI: 10.1093/brain/awv025

"perfusion is REDUCED in the cerebral neocortex in Alzheimer's disease ..."
(emph. added j.t.)

--------------------------------------

16.
Cerebral hypoperfusion and the Energy Deficit in Alzheimer's Disease
By: Seth Love et al.
Brain Pathol. 2016 Sep;26(5):607-17
DOI: 10.1111/bpa.12401

"There is a hypoperfusion DEFICIT in Alzheimer's disease ... the deficit ANTICIPATES the development of dementia, contributes to brain damage, and is caused by both functional and structural abnormalities of the cerebral vasculature ..."
(emph. added j.t.)

Back ↑

--------------------------------------

17.
increasing CEREBRAL BLOOD FLOW improves cognition into late stages in Alzheimer's disease mice
By: Oliver Bracko et al.
J Cereb Blood Flow Metab. 2020 Jul.
DOI: 10.1177/0271678X19873658.

"Alzheimer's disease is associated with a 20-30% reduction in cerebral blood flow."
(emph. added j.t.)

--------------------------------------

18.
"cerebral blood flow REDUCTIONS in Alzheimer's disease patients .. have been recognized for decades ..."
By: Jean C. Cruz, et al.
Nature Neuroscience
volume 22, pages: 413-420 (2019)
(emph. added j.t.)

--------------------------------------

19.
Late-Onset Dementia: Structural Brain Damage and Total CEREBRAL BLOOD FLOW
By: Aart Spilt MD, et al.
RadiologyVolume 236, Issue 3Sep 1 2005

"... blood flowin the brain was 742 milliliters per minute among the healthy, young adults ... among the dementia group was 443 milliliters per minute ... In patients with dementia, cerebral blood flow was 108 mL/min LOWER than that in subjects of the same age with optimal cognitive function ..."
(emph. added j.t.)

--------------------------------------

20.
Vascular risk profiles for dementia and Alzheimer's disease in very old people ...
By: Chengxuan Qiu et al.
J Alzheimers Dis. 2010;20(1):293-300
DOI: 10.3233/JAD-2010-1361

"... INSUFFICIENT perfusion are involved in the DEVELOPMENT of dementia including Alzheimer's disease."
(emph. added j.t.)

--------------------------------------

21.
Risk factors for dementia and Alzheimer's disease ...
By: Cheng-xuan Qiu et al.
Zhonghua Liu Xing Bing Xue Za Zhi 2005 Nov;26(11):882-7

"... vascular DISORDERS ... were MAJOR RISK factors for dementia and Alzheimer's disease ..."
(emph. added j.t.)

Back ↑

--------------------------------------

22.
reduced cerebral blood in Mild Cognitive Impairment Assessed Using Phase-Contrast MRI
By: Reyes Garcia de Eulate et al.
J Alzheimers Dis. 2017;58(2):585-595
DOI: 10.3233/JAD-161222

"There is increasing evidence of a vascular CONTRIBUTION to Alzheimer's disease ..."
(emph. added j.t.)


--------------------------------------

22.1
... Cognitive Dysfunction after Cerebral ischemia*
By: Iris Escobar et al.
J Alzheimers Dis. 2019;67(2):425-446
DOI: 10.3233/JAD-180875

"... cognitive outcomes following cerebral ischemia* ..."

*Brain Ischemia
Cerebral ischemia is defined as a flow of blood to the brain that is
insufficient to meet its metabolic demands, leading to loss of function and CELL DEATH.
(emph. added j.t.)

--------------------------------------

22.2
Neuroimaging studies on cognitive impairment due to cerebral small vessel disease
By: Jing Du et al.
Stroke Vasc Neurol. 2019 Apr 5;4(2):99-101
DOI: 10.1136/svn-2018-000209

"vascular cognitive impairment is a MAJOR CONTRIBUTOR to age-related dementing ..."
(emph. added j.t.)

--------------------------------------

22.3
Sorting out the clinical consequences of ischemic* lesions in brain aging: a clinicopathological approach
By: Gabriel Gold et al.
J Neurol Sci. 2007
DOI: 10.1016/j.jns.2007.01.020

"... vascular lesions that can IMPACT cognitive function ..."

*Brain Ischemia
Cerebral ischemia is defined as a flow of blood to the brain that is
insufficient to meet its metabolic demands, leading to loss of function and CELL DEATH.
(emph. added j.t.)

--------------------------------------

22.4
Longitudinal Cerebral Blood Flow Changes in Normal Aging and the Alzheimer's Disease Continuum Identified by Arterial Spin Labeling MRI
By: Aldo Camargo et al.
J Alzheimers Dis. 2021
DOI: 10.3233/JAD-210116

... cerebral blood flow REDUCTIONS ESCALATED in mild cognitive impairment subjects ...
(emph. added j.t.)

Back ↑

--------------------------------------

22.5
Impaired neurovascular coupling in aging and Alzheimer's disease: Contribution of astrocyte dysfunction and endothelial impairment to cognitive decline
By: Stefano Tarantini et al.
Exp Gerontol. 2017 Aug.
DOI: 10.1016/j.exger.2016.11.004

"... IMPAIRMENT of cerebral microvessels... which likely CONTRIBUTE to neurovascular dysfunction and cognitive decline ..."
(emph. added j.t.)

--------------------------------------

22.6
IGF-1 deficiency impairs neurovascular coupling in mice: implications for cerebromicrovascular aging
By: Peter Toth et al.
Aging Cell. 2015 Dec.
DOI: 10.1111/acel.12372. Epub 2015 Jul 14

... cerebromicrovascular DYSFUNCTION... likely to CONTRIBUTE to cognitive impairment ..."
(emph. added j.t.)

--------------------------------------

22.7
Impaired neurovascular coupling in aging and Alzheimer's disease: Contribution of astrocyte dysfunction and endothelial impairment to cognitive decline
By: Stefano Tarantini et al.
Exp Gerontol. 2017 Aug.
DOI: 10.1016/j.exger.2016.11.004

"... The importance of (micro)vascular CONTRIBUTIONS to cognitive impairment and dementia in aging cannot be overemphasized ..."
(emph. added j.t.)

--------------------------------------

22.8
Neuropsychology of cognitive ageing, minimal cognitive impairment, Alzheimer's disease, and vascular cognitive impairment
By: Jaap Lindeboom et al.
Eur J Pharmacol. 2004 Apr 19;490(1-3):83-6
DOI: 10.1016/j.ejphar.2004.02.046

"... several vascular pathologies can LEAD to cognitive deterioration ... Cerebrovascular disease also plays an IMPORTANT ROLE in forms of cognitive decline ..."
(emph. added j.t.)

--------------------------------------

22.9
Pumps, aqueducts, and drought management: vascular physiology in vascular cognitive impairment
By: Randolph S Marshall et al.
Stroke. 2011 Jan
DOI: 10.1161/STROKEAHA.110.595645

"... Recent evidence, however, suggests that cognitive impairment may be independently MEDIATED by hemodynamic dysfunction, including global and hemispheral hypoperfusion and altered cerebral blood flow regulation ..."
(emph. added j.t.)

Back ↑

--------------------------------------

22.10
Brain atrophy and cognition: interaction with cerebrovascular pathology?
By: Majon Muller et al.
Neurobiol Aging. 2011 May
DOI: 10.1016/j.neurobiolaging.2009.05.005

"... Our findings suggest that patients with cerebrovascular pathology ... may be more VULNERABLE to impairment in executive functioning related to ... focal brain atrophy ..."
(emph. added j.t.)

--------------------------------------

22.11
Cerebral microbleeds and cognition in cerebrovascular disease: an update
By: Andreas Charidimou et al.
J Neurol Sci. 2012 Nov 15;322(1-2):50-5
DOI: 10.1016/j.jns.2012.05.052

"... Sporadic cerebral small vessel disease is a MAJOR CAUSE of cognitive impairment ..."
(emph. added j.t.)


--------------------------------------

22.12
Vascular neuropathology and cognitive decline
By: V Deramecourt
Rev Neurol (Paris) 2013 Oct;169(10):765-71
DOI: 10.1016/j.neurol.2013.07.008

"Cerebrovascular disease is an important CAUSE of cognitive decline and dementia ..."
(emph. added j.t.)

--------------------------------------

22.13
Alzheimer's disease in late-life dementia: a minor toxic consequence of devastating cerebrovascular dysfunction
By: M C Henry-Feugeas
Med Hypotheses 2008;70(4):866-75
DOI: 10.1016/j.mehy.2007.07.027

"... cerebrovascular disease is omnipresent and the CRUCIAL role of microvascular alterations increasingly recognized in late dementia or "Alzheimer syndrome"...."
(emph. added j.t.)

--------------------------------------

22.14
Aspects of ageing in chronic cerebral oligaemia. Mechanisms of degeneration and compensation in rat models
By: K Plaschke. J
Neural Transm (Vienna)2005 Mar;112(3):393-413
DOI: 10.1007/s00702-004-0191-2

"... Cerebral oligaemia may become a stress factor during ageing, LEADING to functional and structural deterioration in the brain ..."
(emph. added j.t.)

Back ↑

--------------------------------------

22.15
Assessing cerebrovascular contribution to late dementia of the Alzheimer's type: the role of combined hemodynamic and structural MR analysis
By: Marie Cecile Henry-Feugeas
J Neurol Sci.2009 Aug 15;283(1-2):44-8
DOI: 10.1016/j.jns.2009.02.325

"... recent neuropathological observations to suggest that the major enemy to combat in late-life dementia IS NOT Alzheimer's disease but cerebrovascular dysfunction ..."
(emph. added j.t.)

--------------------------------------

22.16
Normal aging and cognition: the unacknowledged contribution of cerebrovascular risk factors
By: L Morra et al.
Neuropsychol Dev Cogn B Aging Neuropsychol Cogn.2013;20(3):271-97
DOI: 10.1080/13825585.2012.693905

"... research suggests that part of the variance in age-related cognitive decline is ATTRIBUTABLE to modifiable factors common in geriatric populations such as cerebrovascular risk factors ..."
(emph. added j.t.)

--------------------------------------

22.17
Reduced brain perfusion and cognitive performance due to constitutional hypotension
By: Stefan Duschek et al.
Clin Auton Res. 2007 Apr;17(2):69-76
DOI: 10.1007/s10286-006-0379-7

"... studies demonstrated INSUFFICIENT adjustment of blood flow to cognitive requirements ...:
(emph. added j.t.)

--------------------------------------

22.18
Cognitive impairments in patients with cerebrovascular risk factors: a comparison of Mini Mental Status Exam and Montreal Cognitive Assessment
By: Hajir Sikaroodi et al.
Clin Neurol Neurosurg. 2013 Aug;115(8):1276-80
DOI: 10.1016/j.clineuro.2012.11.026

"... Recent evidence suggests that cerebrovascular risk factors are CONTRIBUTING FACTORS, not only to vascular cognitive decline, but also for Alzheimer's disease ..."
(emph. added j.t.)

--------------------------------------

22.19
Vascular risk factors promote conversion from mild cognitive impairment to Alzheimer disease
By: J Li et al.
Neurology. 2011 Apr 26;76(17):1485-91.
DOI: 10.1212/WNL.0b013e318217e7a4

"... Growing evidence suggests that vascular risk factors CONTRIBUTE to cognitive decline ..."
(emph. added j.t.)

Back ↑

--------------------------------------

22.20
Serum HDL, LDL and total cholesterol in patients with late-life onset of Alzheimer's disease versus vascular dementia
By: Zlatko Trkanjec et al.
Acta Clin Croat. 2009 Sep;48(3):259-63

"... Patients with cerebrovascular risk factors are nowadays recognized as being at an INCREASED RISK of developing cognitive decline ..."
(emph. added j.t.)

--------------------------------------

22.21
The clinical manifestations and pathophysiology of cerebral small vessel disease
By: Ai-Juan Zhang et al.
Neurosci Bull 2010 Jun;26(3):257-64.
DOI: 10.1007/s12264-010-1210-y

"... These [small vessel disease] disorders often CAUSE decline in cognition ..."
(emph. added j.t.)

--------------------------------------

22.22
The role of chronic brain hypoperfusion in the pathogenesis of Alzheimer's disease--facts and hypotheses
By: Denes Zadori et al.
Ideggyogy Sz. 2007 Nov 30;60(11-12):428-37

"...HYPOPERFUSION LEADS to the degeneration of capillaries [in watershed areas of the brain]..."
(emph. added j.t.)

--------------------------------------

22.23
Primary cerebral blood flow deficiency and Alzheimer's disease: shadows and lights
By: Marianna Mazza et al.
J Alzheimers Dis. 2011;23(3):375-89
DOI: 10.3233/JAD-2010-090700

"... It is most likely that a reduction in cerebral blood flow could displace a pathway LEADING to Alzheimer's disease ..."
(emph. added j.t.)


--------------------------------------

22.24
Critically attained threshold of cerebral hypoperfusion: can it cause Alzheimer's disease?
By: J C de la Torre
Ann N Y Acad Sci. 2000 Apr;903:424-36
DOI: 10.1111/j.1749-6632.2000.tb06394.x

"... pathologic events are TRIGGERED in Alzheimer's disease by impaired cerebral perfusion ... INITIATE cognitive dysfunction and neurodegeneration as expressed in Alzheimer's disease brain ... the presence of a condition that LOWERS cerebral perfusion ..."
(emph. added j.t.)

Back ↑

--------------------------------------

22.25
Vascular Cognitive Impairment Caused by Cerebral Small Vessel Disease Is Associated with the TLR4 in the Hippocampus
By: Fulin Gao et al.
J Alzheimers Dis. 2019;70(2):563-572
DOI: 10.3233/JAD-190240

"Cerebral small vessel disease CAN LEAD to leukodystrophy and cognitive impairment ..."
(emph. added j.t.)

--------------------------------------

22.26
Genetic factors in cerebral small vessel disease and their impact on stroke and dementia
By: Christof Haffner et al.
J Cereb Blood Flow Metab. 2016 Jan;
DOI: 10.1038/jcbfm.2015.71

"... Cerebral small vessel disease is among the MOST FREQUENT CAUSES of both stroke and dementia ..."
(emph. added j.t.)

--------------------------------------

22.27
Alzheimer disease as a vascular disorder: nosological evidence
By: J C de la Torre
Stroke. 2002 Apr;33(4):1152-62
DOI: 10.1161/01.str.0000014421.15948.67

"... epidemiological studies showing that practically all risk factors for Alzheimer disease reported thus far have a vascular component that REDUCES cerebral perfusion ..."

"... The collective data presented in this review STRONGLY SUPPORT the concept that sporadic Alzheimer disease is a vascular disorder ..."
(emph. added j.t.)

--------------------------------------

22.28
Management of cerebral small vessel disease for the diagnosis and treatment of dementia
By: Masafumi Ihara
Brain Nerve. 2013 Jul;65(7):801-9

".... cerebral small vessel disease has received much attention as an IMPORTANT CAUSE of dementia ..."
(emph. added j.t.)

--------------------------------------

22.29
Sleep as a Novel Biomarker and a Promising Therapeutic Target for Cerebral Small Vessel Disease: A Review Focusing on Alzheimer's Disease and the Blood-Brain Barrier
By: Oxana Semyachkina-Glushkovskaya et al.
Int J Mol Sci. 2020 Aug 31;21(17):6293
DOI: 10.3390/ijms21176293

",,, Cerebral small vessel disease is a LEADING CAUSE of cognitive decline in elderly people and development of Alzheimer's disease ..."
(emph. added j.t.)

Back ↑

--------------------------------------

22.30
Cerebrovascular Disease and Cognitive Outcome in Patients with Cardiac Disease
By: Michelle C Johansen et al.
Semin Neurol. 2021 Aug;41(4):463-472
DOI: 10.1055/s-0041-1726330

"... constantly evolving insights into the vascular CONTRIBUTIONS to cognitive impairment and dementia ..."
(emph. added j.t.)

--------------------------------------

22.31
Vascular cognitive impairment in dementia
By: Christopher D Etherton-Beer
Maturitas. 2014 Oct;79(2):220-6
DOI: 10.1016/j.maturitas.2014.06.004

"... Vascular risk factors and cerebrovascular disease are common CAUSES of dementia ..."
(emph. added j.t.)

--------------------------------------

22.32
Is Alzheimer's disease a neurodegenerative or a vascular disorder? Data, dogma, and dialectics
By: Jack C de la Torre
Lancet Neurol. 2004 Mar;3(3):184-90
DOI: 10.1016/S1474-4422(04)00683-0

"... data supporting Alzheimer's disease as a primary vascular disorder are ... convincing ..."

--------------------------------------

22.33
Neurovascular pathways to neurodegeneration in Alzheimer's disease and other disorders
By: Berislav V Zlokovic
Nat Rev Neurosci. 2011 Nov 3;12(12):723-38
DOI: 10.1038/nrn3114

"... vascular-derived insults might initiate and/or contribute to neuronal degeneration ..."

--------------------------------------

22.34
The close link between brain vascular pathological conditions and neurodegenerative diseases: Focus on some examples and potential treatments
By: Giuseppe Schiro et al.
Vascul Pharmacol. 2022 Feb;142:106951
DOI: 10.1016/j.vph.2021.106951

"... A close relationship is emerging among ... neurodegenerative decline, and ... alterations, dysfunctions, and related diseases of the CEROBRO-VASCULAR system, which contributes in a significative manner to the TRIGGERING and progressing of neurodegenerative diseases ..."
(emph. added j.t.)

Back ↑

--------------------------------------

22.35
Relationship between cognitive function and regulation of cerebral blood flow
By: Shigehiko Ogoh
J Physiol Sci. 2017 May;67(3):345-351
DOI: 10.1007/s12576-017-0525-0

".. cognitive deterioration may be AFFECTED by a decrease in cerebral blood flow as a result of brain ischemia* ..."

*Brain Ischemia Cerebral ischemia is defined as a flow of blood to the brain that is insufficient to meet its metabolic demands, leading to loss of function and CELL DEATH.
(emph. added j.t.)

--------------------------------------

22.36
The progression of cognitive deterioration and regional cerebral blood flow patterns in Alzheimer's disease: a longitudinal SPECT study
By: Haruo Hanyu et al.
J Neurol Sci. 2010 Mar 15;290(1-2):96-101
DOI: 10.1016/j.jns.2009.10.022

".. the rapidly progressing group [of cognitive deterioration] had GREATER regional cerebral blood flow DEFICITS ..."
(emph. added j.t.)

--------------------------------------

22.37
Very-low-frequency oscillations of cerebral hemodynamics and blood pressure are affected by aging and cognitive load
By: Anouk Vermeij et al.
Neuroimage. 2014 Jan 15;85 Pt 1:608-15
DOI: 10.1016/j.neuroimage.2013.04.107

"... DEGENERATION of the vascular system, which may HAVE CONSEQUENCES for regional cerebral blood flow and cognitive performance ..."
(emph. added j.t.)

--------------------------------------

22.38
HYPOPERFUSION of brain parenchyma is associated with the severity of chronic cerebrospinal venous insufficiency in patients with multiple sclerosis: a cross-sectional preliminary report
By: Paolo Zamboni et al.
BMC Med. 2011 Mar 7;9:22
DOI: 10.1186/1741-7015-9-22

"... REDUCED perfusion could contribute to ... DEGENERATED axons ..."
(emph. added j.t.)

--------------------------------------

22.39
The thermodynamic brain
By: Joseph Donnelly et al.
Crit Car. 2014 Dec 12;18(6):693
DOI: 10.1186/s13054-014-0693-8

"... if there is NO high-volume blood flow to cool and stabilize the brain temperature, the possibility of UNSTABLE behavior seems to be high ..."
(emph. added j.t.)

Back ↑

--------------------------------------

22.40
Effect of aging on brain energy-metabolism
By: Nili Zarchin et al.
Comp Biochem Physiol A Mol Integr Physi. 2002 May;132(1):117-20
DOI: 10.1016/s1095-6433(01)00537-2

"... hemodynamic oscillations are related to the DEVELOPMENT of a pathological state and are NOT A NORMAL cerebral function ..."
(emph. added j.t.)

--------------------------------------

22.41
Dose-dependent association of accelerometer-measured physical activity and sedentary time with brain perfusion in aging
By: Zvinka Z Zlatar et al.
Exp Gerontol. 2019 Oct 1;125:110679
DOI: 10.1016/j.exger.2019.110679

"... Age-related decreases in CEREBRAL BLOOD FLOW may LEAD to cognitive decline ..."
(emph. added j.t.)

--------------------------------------

22.42
Increasing cerebral blood flow improves cognition into late stages in Alzheimer's disease mice
By: Oliver Bracko et al.
J Cereb Blood Flow Metab. 2020 Jul;40(7):1441-1452
DOI: 10.1177/0271678X19873658

"... Alzheimer's disease is associated with a 20-30% reduction in cerebral blood flow ...
... growing body of evidence suggesting that cerebral blood flow reductions are an IMPORTANT CONTRIBUTING FACTOR to the cognitive dysfunction associated with neurodegenerative disease ..."
(emph. added j.t.)

--------------------------------------

22.43
Genetic Factors of Cerebral Small Vessel Disease and Their Potential Clinical Outcome
By: Vo Van Giau et al.
Int J Mol Sci. 2019 Sep 3;20(17):4298
DOI: 10.3390/ijms20174298

"... Cerebral small vessel diseases have been causally correlated with ischemic strokes, LEADING TO cognitive decline and vascular dementia ..."
(emph. added j.t.)

--------------------------------------

22.44
Frontal dynamic activity as a predictor of cognitive dysfunction after pontine ischemia
By: Shigeru Obayashi
NeuroRehabilitation 2019;44(2):251-261
DOI: 10.3233/NRE-182566

"... cognitive DYSFUNCTION after pontine ischemia* ..."

*Brain Ischemia
Cerebral ischemia is defined as a flow of blood to the brain that is
insufficient to meet its metabolic demands, leading to loss of function and CELL DEATH.
(emph. added j.t.)

--------------------------------------

22.45
Detecting perfusion deficit in Alzheimer's disease and mild cognitive impairment patients by resting-state fMRI
By: Shaozhen Yan et al.
J Magn Reson Imaging. 2019 Apr;49(4):1099-1104
DOI: 10.1002/jmri.26283

"... HYPOPERFUSION are IMPLICATED in the risk of developing Alzheimer's disease ..."
(emph. added j.t.)

--------------------------------------

22.46
Vascular dementia and Alzheimer's disease - are we in a dead-end road?
By: Margherita Cavalieri et al.
Neurodegener Dis. 2010;7(1-3):122-6
DOI: 10.1159/000285521

"... most Alzheimer's disease cases present with AT LEAST SOME vascular brain lesions ..."
"... vascular lesions, even if subtle, EXERT SIGNIFICANT EFFECTS on the patients' cognitive functioning ..."
(emph. added j.t.)

--------------------------------------

22.47
Vascular dementia: still a debatable entity?
By: C Loeb et al.
J Neurol Sci. 1996 Nov;143(1-2):31-40
DOI: 10.1016/s0022-510x(96)00191-8

"... Vascular dementia is a clinical entity, identifiable in at least 30-70% of patients AFTER STROKES ..."
(emph. added j.t.)

--------------------------------------

22.48
Vascular dementia: a changing concept
By: M Hennerici
Arzneimittelforschung. 1995 Mar;45(3A):366-70.

"... REDUCTION OF CEREBRAL BLOOD FLOW leading to neuronal death, cerebral atrophy, and finally dementia ..."
(emph. added j.t.)

--------------------------------------

22.49
The Impact of Low Hemoglobin Levels on Cognitive Brain Functions
By: Boula S Gattas et al.
Cureus. 2020 Nov 8;12(11):e11378
DOI: 10.7759/cureus.11378

"... currently conducted studies support the idea that anemia is a SIGNIFICANT RISK factor for dementia ... ... anemia CAUSES a decrease in cognitive brain functions ..."
(emph. added j.t.)

Back to: "root cause, of Alzheimer's disease and dementia"↑

--------------------------------------

23.
Vascular neuropathology and cognitive decline
By: V Deramecourt
Rev Neurol (Paris) 2013 Oct;169(10):765-71
DOI: 10.1016/j.neurol.2013.07.008

"... The diagnosis of these conditions [vascular or mixed dementia] still RELIES ON both clinical and neuropathological EXPERTISE ..."
(emph. added j.t.)

Back to: "blood-pressure measurement"↑

--------------------------------------

24.
Clinically asymptomatic vascular brain injury: a potent cause of cognitive impairment among older individuals
By: Charles DeCarli
J Alzheimers Dis. 2013;33 Suppl 1(0 1):S417-26
DOI: 10.3233/JAD-2012-129004

"... various vascular risk factors continues to rise and many are UNDIAGNOSED OR UNDERTREATED ..."
(emph. added j.t.)

--------------------------------------

24.1
A preclinical phase in vascular dementia: cognitive impairment three YEARS BEFORE diagnosis
By: Sari Jones et al.
Dement Geriatr Cogn Disord. 2004;18(3-4):233-9
DOI: 10.1159/000080021

"... This observation suggests that circulatory disturbance is associated with cognitive problems SEVERAL YEARS BEFORE the actual vascular dementia diagnosis ..."
(emph. added j.t.)

--------------------------------------

24.2
Cerebrovascular and Alzheimer disease: fellow travelers or partners in crime?
By: Antonia Nucera et al.
J Neurochem. 2018 Mar;144(5):513-516:
DOI: 10.1111/jnc.14283

"... vascular cognitive impairment may often go unrecognized ... and is RELATED to cognitive impairment and dementia ..."
(emph. added j.t.)

--------------------------------------

24.3
Clinically asymptomatic vascular brain injury: a potent cause of cognitive impairment among older individuals
By: Charles DeCarli
J Alzheimers Dis. 2013;33 Suppl 1(0 1):S417-26
DOI: 10.3233/JAD-2012-129004

"... the prevalence of individuals with various vascular risk factors continues to rise and many are UNDIAGNOSED OR UNDERTREATED ..."
(emph. added j.t.)

--------------------------------------

24.4
Alzheimer's disease prevention: A way forward
By: F Bermejo-Pareja et al.
Rev Clin Esp (Barc). 2016 Dec;216(9):495-503.
DOI: 10.1016/j.rce.2016.05.010

"... Treatment failure is likely due to the fact that Alzheimer's disease GESTATES IN THE BRAIN FOR DECADES but manifests in old age ..."
(emph. added j.t.)

--------------------------------------

24.5
Healthy Aging and Dementia: Two Roads Diverging in Midlife?
By: Katie Irwin et al.
Front Aging Neurosci. 2018 Sep 19;10:275
DOI: 10.3389/fnagi.2018.00275

"... MIDLIFE as a critical period for the BEGINNING OF ALZHEIMER disease-related pathology ..."
(emph. added j.t.)

Back to: "lingers on silently for years without being directly detected"↑

--------------------------------------

25.
White matter integrity in small VESSEL disease is related to cognition
By: Anil M Tuladhar et al.
Neuroimage Clin. 2015 Feb 16;7:518-24
DOI: 10.1016/j.nicl.2015.02.003

"Cerebral small vessel disease ... is common in elderly people and is RELATED to cognitive impairment and dementia ..."
(emph. added j.t.)

--------------------------------------

26
A rat model of mild cognitive impairment associated with vascular factor
By: Li Zhang et al.
Neuropathology. 2011 Apr
DOI: 10.1111/j.1440-1789.2010.01137.x

"Vascular factors have been shown to be IMPORTANT in cognitive impairment and dementia in the elderly ..."
(emph. added j.t.)

--------------------------------------

27
The impact of cerebrovascular aging on vascular cognitive impairment and dementia
By: Tuo Yang et al.
Ageing Res Rev. 2017 Mar;34:15-29 DOI: 10.1016/j.arr.2016.09.00

"... aging within blood vessels contributes to a decrease in blood flow ... eventually RESULTING in cognitive and sensorimotor decline ..."
(emph. added j.t.)

--------------------------------------

27.1
Critically attained threshold of cerebral hypoperfusion: can it cause Alzheimer's disease?
By: J C de la Torre
Ann N Y Acad Sci. 2000 Apr;903:424-36
DOI: 10.1111/j.1749-6632.2000.tb06394.x

"... cognitive dysfunction and neurodegeneration as expressed in Alzheimer's disease brain: advanced aging normal but potentially deconstructing process that LOWERS cerebral blood flow in proportion to INCREASED aging ..."
(emph. added j.t.)

--------------------------------------

27.2
Neuropsychology of cognitive ageing, minimal cognitive impairment, Alzheimer's disease, and vascular cognitive impairment
By: Jaap Lindeboom et al.
Eur J Pharmacol. 2004 Apr 19;490(1-3):83-6


"... It may be concluded that cognitive decline IS NOT an inevitable outcome of ageing ..."
(emph. added j.t.)

Back to: "condition is fairly common in the elderly"↑

--------------------------------------

28.
Periodontal disease's contribution to Alzheimer's disease progression in Down syndrome
By: Angela R. Kamer et al.
Alzheimer's & Dementia: Volume 2, Issue 1 p. 49-57
DOI: 10.1016/j.dadm.2016.01.001

"Alzheimer's disease is a continuous process whose pathology starts YEARS BEFORE the onset of dementia ..."
(emph. added j.t.)


--------------------------------------

28.1
"Early-onset Alzheimer's disease occurs between a person's 30s and mid-60s"

National Institute on Aging
National Institutes of Health
https://www.nia.nih.gov/health/alzheimers-disease-fact-sheet

--------------------------------------

28.2
The Road Ahead to Cure Alzheimer's Disease: Development of Biological Markers and Neuroimaging Methods for Prevention Trials Across all Stages and Target Populations
By: E Cavedo et al.
J Prev Alzheimers Dis actions. 2014 Dec;1(3):181-202
DOI: 10.14283/jpad.2014.32

"Alzheimer's disease ... biological markers, PRECEDE overt clinical symptoms by many YEARS to DECADES."
(emph. added j.t.)

--------------------------------------

28.3
"Alzheimer's disease begins LONG BEFORE any symptoms become apparent ... This stage of Alzheimer's can last for YEARS, possibly even DECADES."

By Mayo Clinic Staff https://www.mayoclinic.org/diseases-conditions/alzheimers-disease/in-depth/alzheimers-stages/art-20048448
(emph. added j.t.)

--------------------------------------

28.4
Cerebral blood flow measured by arterial spin labeling MRI as a preclinical marker of Alzheimer's disease
By: Christina E Wierenga et al.
J Alzheimers Dis. 2014
DOI: 10.3233/JAD-141467

"... cerebral hypoperfusion changes are present several YEARS BEFORE the development of the clinical symptoms of Alzheimer's disease ..."
(emph. added j.t.)

--------------------------------------

28.5
"... brain blood flow DEFICITS are one of the EARLIEST detectable symptoms of dementia"
By: Jean C.Cruz Hernandez et al.
published in Nature Neuroscience
(emph. added j.t.)

Back ↑

--------------------------------------

28.6
"cerebral blood flow ... is useful in the EARLY diagnosis of dementia"
By: Niwa F, et al.
Intern Med. 2016;55(24):3571-3578. Epub 2016 Dec 15
(emph. added j.t.)

--------------------------------------

28.7.
... Elderly Subjects with Subjective Cognitive Impairment
By: Fumitoshi Niwa et al.
Intern Med. 2016;55(24):3571-3578
DOI: 10.2169/internalmedicine.55.6725

"... cerebral blood flow ... is useful in the EARLY diagnosis of dementia ..."
(emph. added j.t.)

--------------------------------------

28.8
Cerebral blood flow changes during aging process and in cognitive disorders: A review
By: Naghmeh Mokhber et al.
Neuroradiol J. 2021 Aug.
DOI: 10.1177/19714009211002778

"... it is possible that cerebral blood flow REDUCTION might PRECEDE cognitive decline ..."
(emph. added j.t.)

--------------------------------------

28.9
Risk factors and neurodegenerative mechanisms in stroke related dementia
By: R N Kalaria
Panminerva Med. 2012 Sep;54(3):139-48

"... Considerable evidence indicates that systemic vascular diseases are associated with neurodegenerative processes PRECEDING cognitive decline and dementia ..."
(emph. added j.t.)

--------------------------------------

28.9.1
Assessing cognition and function in Alzheimer's disease clinical trials: do we have the right tools?
By : Peter J Snyder et al.
Alzheimers Dement. 2014 Nov;10(6):853-60
DOI: 10.1016/j.jalz.2014.07.158

"... biological changes associated with Alzheimer's disease are occurring possibly SEVERAL DECADES BEFORE an individual will experience the cognitive and functional changes associated with the disease ..."
(emph. added j.t.)

Back ↑

--------------------------------------

28.9.2
Midlife interventions are critical in prevention, delay, or improvement of Alzheimer's disease and vascular cognitive impairment and dementia
By: Sam Gandy et al.
F1000Res. 2017 Apr 3;6:413
DOI: 10.12688/f1000research.11140.1. eCollection 2017

"... evidence has accrued pointing to dementias as late-life clinical phenotypes THAT BEGIN AS MIDLIFE pathologies ..."
(emph. added j.t.)

--------------------------------------

28.9.3
Integrating Health Promotion Into Physical Therapy Practice to Improve Brain Health and Prevent Alzheimer Disease
By: Ellen McGough et al.
Neurol Phys Ther. 2017 Jul;41 Suppl 3:S55-S62
DOI: 10.1097/NPT.0000000000000181

"... Alzheimer disease is the most common cause of dementia, and brain pathology APPEARS YEARS BEFORE symptoms are evident ..."
(emph. added j.t.)

Back to: "way before any symptoms of dementia manifest themselves" ↑

--------------------------------------

29.
Cerebrovascular disease in ageing and Alzheimer's disease
By: Seth Love et al.
Acta Neuropathol
2016 May;131(5):645-58
DOI: 10.1007/s00401-015-1522-0

"Cerebrovascular disease and Alzheimer's disease have more in common THAN THEIR ASSOCIATION with ageing ..."
(emph. added j.t.)

--------------------------------------

29.1
Cerebral blood flow measured by arterial spin labeling MRI as a preclinical marker of Alzheimer's disease
By: Christina E Wierenga et al.
J Alzheimers Dis. 2014
DOI: 10.3233/JAD-141467

"... cerebral hypoperfusion has been shown to DISTINGUISH between cognitively normal individuals, ADULTS AT RISK for Alzheimer's disease, and persons diagnosed with Alzheimer's disease..."
(emph. added j.t.)

Back ↑

--------------------------------------

30.
Brain temperature and cerebral blood flow imaging in patients with severe subarachnoid hemorrhage: report of two cases
By: Yasunari Otawara et al.
Surg Neurol. 2003 Dec;60(6):549-52; discussion 552
DOI: 10.1016/s0090-3019(03)00293-3

"... ABSENCE of brain perfusion ... causing IRREVERSIBLE brain damage ..."
(emph. added j.t.)

--------------------------------------

30.1
Cardiac disorders and cognitive impairment in patients with chronic cerebral ischemia
By: E G Semushkina et al.
Zh Nevrol Psikhiatr Im S S Korsakova. 2013;113(2):9-13

"... atherosclerosis of brain vessels ... PREDICTED COGNITIVE IMPAIRMENT in patients with chronic brain ischemia. Reduced left ventricular ejection fraction was the main cardiac factor determining the severity ..."
(emph. added j.t.)

Back to: "unless promptly treated for the condition"↑

--------------------------------------

31.
Reduced Cerebral Blood Flow in Mild Cognitive Impairment Assessed Using Phase-Contrast MRI
By: Reyes Garcia de Eulate et al.
J Alzheimers Dis. 2017;58(2):585-595
DOI: 10.3233/JAD-161222

... "A quantitative MEASUREMENT of total brain blood flow could potentially predict vascular dysfunction and compromised brain perfusion in early stages of Alzheimer's disease ..."
(emph. added j.t.)

--------------------------------------

31.1
Living beyond our physiological means: small vessel disease of the brain is an expression of a systemic failure in arteriolar function: a unifying hypothesis
By: Charlie S Thompson et al.
Stroke 2009 May;40(5):e322-30
DOI: 10.1161/STROKEAHA.108.542266

"... small vessel disease is a systemic condition with MAJOR healthcare consequences, requiring A NEW paradigm in the way we practice medicine ..."
(emph. added j.t.)

Back to: "similar to how blood-pressure is routinely tested"↑

--------------------------------------

32.
How Treatable is Vascular Dementia?
By: Etsuro Mori
Brain Nerve. 2016 Apr;68(4):441-50
DOI: 10.11477/mf.1416200417

"... Vascular dementia is preventable and treatable ..."


--------------------------------------

32.1
Antegrade selective cerebral perfusion ...
By: Davide Pacini et al.
Eur J Cardiothorac Surg. 2007 Apr;31(4):618-22
DOI: 10.1016/j.ejcts.2006.12.032

"... cerebral perfusion has been demonstrated to be the best method of protection of brain ischemia* ..."

*Brain Ischemia
Cerebral ischemia is defined as a flow of blood to the brain that is
insufficient to meet its metabolic demands, leading to loss of function and CELL DEATH.
(emph. added j.t.)

--------------------------------------

32.1.1
Cerebral Blood Flow Measurements in Adults ...
By: Peter J Joris et al.
Nutrients. 2018
DOI: 10.3390/nu10050530

"... Improving cerebrovascular function may be a key mechanism ... [and a] cornerstone [that] protects against cognitive impairments ... increases in perfusion may contribute to the beneficial effects on cognitive functioning ..."

--------------------------------------

32.1.2
Role of age-related alterations of the cerebral venous circulation in the pathogenesis of vascular cognitive impairment
By: Gabor A Fulop et al.
Am J Physiol Heart Circ Physiol. 2019
DOI: 10.1152/ajpheart.00776.2018

"... Understanding the age-related functional and phenotypic alterations of the cerebral venous circulation is critical for DEVELOPING NEW PREVENTIVE, diagnostic, and therapeutic approaches TO PRESERVE brain health in older individuals ..."
(emph. added j.t.)

--------------------------------------

32.1.3
Treatment with the mitochondrial-targeted antioxidant peptide SS-31 rescues neurovascular coupling responses and cerebrovascular endothelial function and improves cognition in aged mice
By: Stefano Tarantini et al.
Aging Cell. 2018 Apr.
DOI: 10.1111/acel.12731. Epub 2018 Feb 6

"Moment-to-moment adjustment of cerebral blood flow ... has an essential role in MAINTENANCE of healthy cognitive function ..."
(emph. added j.t.)

Back↑

--------------------------------------

32.1.4
Pumps, aqueducts, and drought management: vascular physiology in vascular cognitive impairment
By: Randolph S Marshall et al.
Stroke. 2011 Jan
DOI: 10.1161/STROKEAHA.110.595645

"... treatments proposed to CORRECT impaired vascular physiology may reasonably be expected to treat the cognitive dysfunction ..."
(emph. added j.t.)

--------------------------------------

32.1.5
Clinically asymptomatic vascular brain injury: a potent cause of cognitive impairment among older individuals
By: Charles DeCarli
J Alzheimers Dis. 2013;33 Suppl 1(0 1):S417-26
DOI: 10.3233/JAD-2012-129004

"... Results of this review emphasize the need for EARLY detection and treatment of vascular risk factors to improve the cognitive health of our rapidly aging population ..."
(emph. added j.t.)

--------------------------------------

32.1.6
Living beyond our physiological means: small vessel disease of the brain is an expression of a systemic failure in arteriolar function: a unifying hypothesis
By: Charlie S Thompson et al.
Stroke 2009 May;40(5):e322-30
DOI: 10.1161/STROKEAHA.108.542266.

"... this condition [small vessel disease] can be DECELERATED by control of vascular risk factors ..."
(emph. added j.t.)

--------------------------------------

32.1.7
Vascular contributions to cognitive impairment and dementia including Alzheimer's disease
By: Heather M Snyder et al.
Alzheimers Dement.2015 Jun;11(6):710-7
DOI: 10.1016/j.jalz.2014.10.008

"... study, prevent, diagnose and TREAT age-associated cognitive deficits ..."
(emph. added j.t.)

--------------------------------------

32.1.8
Cerebrovascular and Alzheimer disease: fellow travelers or partners in crime?
By: Antonia Nucera et al.
J Neurochem. 2018 Mar;144(5):513-516
DOI: 10.1111/jnc.14283. Epub 2018 Jan 25

"... because vascular risk factors are treatable, it should be possible to PREVENT or delay some dementias ..."
(emph. added j.t.)

Back↑

--------------------------------------

32.1.9
Vascular Cognitive Impairment
By: Martin Dichgans et al.
Circ Res. 2017 Feb 3;120(3):573-591
DOI: 10.1161/CIRCRESAHA.116.308426

"... there is increasing awareness that targeting vascular risk may help to PREVENT dementia, even of the Alzheimer type ..."
(emph. added j.t.)

--------------------------------------

32.1.10
Alzheimer disease as a vascular disorder: nosological evidence
By: J C de la Torre
Stroke. 2002 Apr;33(4):1152-62
DOI: 10.1161/01.str.0000014421.15948.67

"... It is recommended that current clinical management of patients ... DISEASE PREVENTION efforts need to be critically reassessed and placed in perspective in light of these important findings [that Alzheimer disease should be classified as a vascular disorder] ..."
(emph. added j.t.)

--------------------------------------

32.1.11
Cerebrovascular Disease and Cognitive Outcome in Patients with Cardiac Disease
By: Michelle C Johansen et al.
Semin Neurol. 2021 Aug;41(4):463-472
DOI: 10.1055/s-0041-1726330

"... Alzheimer's disease leading to a heightened emphasis on disease PREVENTION through EARLY and aggressive control of vascular risk factors."
(emph. added j.t.)

--------------------------------------

32.1.12
Alzheimer's disease: cardiovascular risk factors must be assessed
By: Antoine et al.
Rev Med Interne. 2006 Jan;27(1):21-31
DOI: 10.1016/j.revmed.2005.04.037

"... cardiovascular risk factors, as a PREVENTABLE CAUSE, either of cognitive decline, morbidity and mortality ..."
(emph. added j.t.)

--------------------------------------

32.1.13
Neurovascular pathways to neurodegeneration in Alzheimer's disease and other disorders
By: Berislav V Zlokovic
Nat Rev Neurosci. 2011 Nov 3;12(12):723-38
DOI: 10.1038/nrn3114

"... therapeutic opportunities relating to ... neurovascular deficits ..."

Back↑

--------------------------------------

32.1.14
New concepts of pathogenesis, diagnosis, and treatment of neurodegenerative diseases
By: M V Ugriumov
Vestn Ross Akad Med Nauk. 2010
PMID: 20919532

"...necessity to develop preclinical diagnostics and PREVENTIVE THERAPY aimed at arresting or at least slowing down of the neurodegenerative process and prolongation of the preclinical stage for many years ..."
(emph. added j.t.)

--------------------------------------

32.1.15
Impact of multisession 40Hz tACS on hippocampal perfusion in patients with Alzheimer's disease
By: Giulia Sprugnoli et al.
Alzheimers Res Ther. 2021 Dec 20;13(1):203
DOI: 10.1186/s13195-021-00922-4

"... transcranial alternating current stimulation ... INCREASE PERFUSION in critical brain areas in Alzheimer's disease patients ..."
(emph. added j.t.)

--------------------------------------

32.1.16
Vascular dementia: a diagnosis running out of time
By: Robert Stewart
Br J Psychiatry. 2002 Feb;180:152-6
DOI: 10.1192/bjp.180.2.152

"... modification of vascular risk represents a potentially powerful means to PREVENT dementia ..."
(emph. added j.t.)

--------------------------------------

32.1.17
Vascular dementia, hypertension, and the brain
By: C G Lis et al.
Neurol Res. 1997 Oct;19(5):471-80.
DOI: 10.1080/01616412.1997.11740844

"... Vascular dementias are potentially preventable ..."
(emph. added j.t.)

--------------------------------------

32.1.18
Possibilities of Dementia Prevention - It is Never Too Early to Start
By: Sandra Morovic et al.
J Med Life. 2019 Oct-Dec;12(4):332-337
DOI: 10.25122/jml-2019-0088

"--- A large number of dementia cases are POTENTIALLY PREVENTABLE BY EARLY INTERVENTION ...
... careful control of vascular risk factors can POSTPONE THE ONSET or even reverse disease progression ..."
(emph. added j.t.)

Back to: "correct the condition of cerebral hypo-perfusion, where it occurs"↑

--------------------------------------

32.2
MRS shows abnormalities before symptoms in familial Alzheimer disease
By: A K Godbolt et al.
Neurology. 2006 Mar 14;66(5):718-22.
DOI: 10.1212/01.wnl.0000201237.05869.df

"... Pathologic change in Alzheimer disease begins some YEARS BEFORE symptoms ..."
(emph. added j.t.)

--------------------------------------

33.
Midlife risk score for the prediction of dementia FOUR DECADES later
By: Lieza G Exalto et al.
Alzheimers Dement. 2014 Sep;10(5):562-70
DOI: 10.1016/j.jalz.2013.05.1772

"... vascular risk factors in MIDLIFE is highly predictive of the likelihood of dementia DECADES later ..."
(emph. added j.t.)

--------------------------------------

34.
Is late-onset Alzheimer's disease really a disease of midlife?
By: Karen Ritchie et al.
Alzheimers Dement (NY). 2015 Jul 26;1(2):122-130
DOI: 10.1016/j.trci.2015.06.004

"Increasing evidence suggests that Alzheimer's disease may begin DECADES before evidence of dementia, indicating that it may be a disorder of midlife rather than old age."
(emph. added j.t.)

--------------------------------------

35.
Midlife vascular risk factors and their association with dementia ...
By: Bjorn Heine Strand et al.
J Neurol Sci. 2013 Jan 15;324(1-2):124-30
DOI: 10.1016/j.jns.2012.10.018

"There is growing evidence that MIDLIFE risk factors for vascular disease also are risk factors for dementia ..."
(emph. added j.t.)

Back ↑

--------------------------------------

36.
Alzheimer's disease
By: Vanessa J De-Paula et al.
Subcell Biochem. 2012;65:329-52
DOI: 10.1007/978-94-007-5416-4_14

"... recent evidence indicate that [pre-symptomatic (or pre-clinical) Alzheimer's disease] may be OBSERVED in some subjects as EARLY as in the third or fourth decades of life ..."
(emph. added j.t.)

--------------------------------------

37.
Senile dementia and Alzheimer's disease. Brain blood flow and metabolism
By: S Hoyer
Prog Neuropsychopharmacol Biol Psychiatry. 1986;10(3-5):447-78
DOI: 10.1016/0278-5846(86)90018-7

"--- Blood flow --- of the NORMALLY AGED brain maintained UNCHANGED from the 3rd to the 7th decade of life. ---"
(emph. added j.t.)

--------------------------------------

38.
Prevalence of cerebral amyloid pathology in persons without dementia: a meta-analysis
By: Willemijn J Jansen et al.
JAMA. 2015 May 19;313(19):1924-38
DOI: 10.1001/jama.2015.4668

... "These findings suggest a 20- to 30-year interval between first development of amyloid positivity and onset of dementia." ...


--------------------------------------

38.1
Cerebral blood flow measured by arterial spin labeling MRI as a preclinical marker of Alzheimer's disease
By: Christina E Wierenga et al.
J Alzheimers Dis. 2014
DOI: 10.3233/JAD-141467

"... cerebral hypoperfusion may even be sensitive for PREDICTING cognitive decline and conversion to mild cognitive impairment and Alzheimer's disease over time ...."
(emph. added j.t.)

--------------------------------------

38.2
"Boomerang Neuropathology" of Late-Onset Alzheimer's Disease is Shrouded in Harmful "BDDS": Breathing, Diet, Drinking, and Sleep During Aging
By: Mak Adam Daulatzai
DOI: 10.1007/s12640-015-9528-x

"Brain damage begins YEARS BEFORE substantial neurodegeneration and Alzheimer's dementia."
(emph. added j.t.)

Back to: "Alzheimer's disease and dementia, at a much later age."↑

--------------------------------------

39.
Acetylcholinesterase inhibitors and risk of stroke and death in people with dementia
By: Edwin C.K.Tanab et al.
DOI: 10.1016 j.jalz 2018.02.011

"... risk of ischemic* stroke and death in people with dementia."

*Brain Ischemia
Cerebral ischemia is defined as a flow of blood to the brain that is
insufficient to meet its metabolic demands, leading to loss of function and CELL DEATH.

--------------------------------------

40.
Mitochondria as a primary target for vascular hypoperfusion and oxidative stress in Alzheimer's disease
By: Gjumrakch Aliev et al.
Mitochondrion. 2004 Sep;4(5-6):649-63
DOI: 10.1016/j.mito.2004.07.018

... hypoperfusion ... leads to NEURONAL DEATH which manifests as cognitive impairment and the development of brain pathology as in Alzheimer's disease ...
(emph. added j.t.)

--------------------------------------

40.1
Brain temperature: from physiology and pharmacology to neuropathology
By: Eugene A Kiyatkin
Handb Clin Neurol. 2018;157:483-504
DOI: 10.1016 B978-0-444-64074-1.00030-6

"... hyperthermia can reach pathologic levels, resulting in irreversible damage of brain cells ..."

--------------------------------------

40.2
Impaired neurovascular coupling in aging and Alzheimer's disease: CONTRIBUTION of astrocyte dysfunction and endothelial impairment to cognitive decline
By: Stefano Tarantini et al.
Exp Gerontol. 2017 Aug.
DOI: 10.1016/j.exger.2016.11.004

"... the picture emerges of a complex functional impairment of cerebral microvessels and astrocytes, which likely CONTRIBUTE to neurovascular dysfunction and cognitive decline ..."
(emph. added j.t.)

--------------------------------------

40.3
Role of age-related alterations of the cerebral venous circulation in the pathogenesis of vascular COGNITIVE IMPAIRMENT
By: Gabor A Fulop et al.
Am J Physiol Heart Circ Physiol. 2019
DOI: 10.1152/ajpheart.00776.2018

"There has been an INCREASING APPRECIATION of the role of vascular contributions to cognitive impairment and dementia associated with old age. Strong preclinical and translational evidence LINKS age-related dysfunction and structural alterations of the cerebral arteries, arterioles, and capillaries to the PATHOGENESIS of many types of dementia in the elderly, including Alzheimer's disease ..."
(emph. added j.t.)

--------------------------------------

40.4
The role of chronic brain hypoperfusion in the pathogenesis of Alzheimer's disease--facts and hypotheses
By: Denes Zadori et al.
Ideggyogy Sz. 2007 Nov 30;60(11-12):428-37

"... development of HYPOPERFUSION and its consequences in the watershed areas of the brain and the NEURODEGENERATIVE process of the neuronal system ..."
(emph. added j.t.)

Back to: "liable to result in damage to brain-cells"↑

--------------------------------------

41.
Astroglial and Cognitive Effects of CHRONIC Cerebral Hypoperfusion in the Rat
By: Evelin Vicente et al.
Brain Res. 2009 Jan 28;1251:204-12
DOI: 10.1016/j.brainres.2008.11.032

"significant reduction of cerebral blood flow (hypoperfusion) in rats ... constitutes a well established experimental model to investigate neuronal damage and cognitive impairment that occurs in human ageing and Alzheimer's disease ..."
(emph. added j.t.)

--------------------------------------

42.
From CHRONIC cerebral hypoperfusion to Alzheimer-like brain pathology and neurodegeneration
By: Yang Zhao et al.
Cell Mol Neurobiol. 2015 Jan
DOI: 10.1007/s10571-014-0127-9

"Recent studies have revealed an important role of CHRONIC cerebral hypoperfusion in neurodegeneration and dementia, including vascular dementia and Alzheimer's disease ..."
(emph. added j.t.)

--------------------------------------

43.
... CHRONIC cerebral hypoperfusion-related neurodegenerative diseases ...
By: Eszter Farkas et al.
Brain Res Rev
2007 Apr;54(1):162-80
DOI: 10.1016/j.brainresrev.2007.01.003

"... the pattern of cerebral blood flow in mild cognitive impairment has emerged as a predictive marker for the progression into Alzheimer's disease ..."
(emph. added j.t.)

--------------------------------------

44.
... Aged Rats Subjected to CHRONIC Cerebral Hypoperfusion
By: Amanda Santiago et al.
Neuropharmacology 2018 Aug;138:360-370
DOI: 10.1016/j.neuropharm.2018.06.019

"CHRONIC cerebral hypoperfusion has been associated with aging-related vascular dementia, including Alzheimer's disease ..."
(emph. added j.t.)

--------------------------------------

45.
CHRONIC brain hypoperfusion: a key mechanism leading to vascular cognitive impairment and dementia
By: Jessica Duncombe et al.
Clin Sci (Lond)
2017 Sep 28;131(19):2451-2468
DOI: 10.1042/CS20160727

"... it appears that cerebral hypoperfusion is the common underlying pathophysiological mechanism which is a major contributor to cognitive decline and degenerative processes leading to dementia ..."
(emph. added j.t.)

Back ↑

--------------------------------------

46.
CHRONIC cerebral hypoperfusion alters Beta Amyloid peptide pools leading to cerebral amyloid ...
By: Natalia Salvadores et al.
Clin Sci (Lond)
2017 Jul 24;131(16):2109-2123
DOI: 10.1042/CS20170962

"Cerebral hypoperfusion is an early feature of Alzheimer's disease ..."
(emph. added j.t.)

--------------------------------------

47.
The role of CHRONIC brain hypoperfusion in the pathogenesis of Alzheimer's disease--facts and hypotheses
By: Denes Zadori et al.
Ideggyogy Sz.
2007 Nov 30;60(11-12):428-37

"... [brain] hypoperfusion leads to the degeneration of capillaries ..."
(emph. added j.t.)

--------------------------------------

48.
The impact of cerebrovascular aging on vascular cognitive impairment and dementia
By: Tuo Yang et al.
Ageing Res Rev.
2017 Mar;34:15-29
DOI: 10.1016/j.arr.2016.09.007

"... One of the major of types of cognitive dysfunction due to CHRONIC cerebral hypoperfusion is vascular cognitive impairment and dementia ..."
(emph. added j.t.)

--------------------------------------

49.
CHRONIC cerebral hypoperfusion alters Beta Amyloid peptide pools leading to cerebral amyloid ...
By: Natalia Salvadores et al.
Clin Sci (Lond)
2017 Jul 24;131(16):2109-2123
DOI: 10.1042/CS20170962

"We suggest that in response to hypoperfusion, increased beta amyloid production/deposition ..."
(emph. added j.t.)

--------------------------------------

50.
Neurovascular coupling preserved in a CHRONIC mouse model of Alzheimer's disease ...
By: Paul S Sharp et al.
J Cereb Blood Flow Metab. 2020 Nov.
DOI: 10.1177/0271678X19890830

"... impaired neurovascular coupling has been suggested as an early pathogenic factor in Alzheimer's disease, which could serve as an early biomarker of cerebral pathology ..."
(emph. added j.t.)

Back ↑

--------------------------------------

51.
Are Major Dementias Triggered by Poor Blood Flow to the Brain?
By: Jack C de la Torre
J Alzheimers Dis. 2017 57 (2), 353-371
DOI: 10.3233/JAD-161266

"There is growing evidence that CHRONIC brain hypoperfusion plays a central role in the development of Alzheimer's disease long before dyscognitive symptoms or amyloid accumulation in the brain appear ..."
(emph. added j.t.)

--------------------------------------

52.
... CHRONIC cerebral hypoperfusion ...
By: Xiao-Li He et al.
Brain Res. 2009 Jan 16;1249:212-21
DOI: 10.1016/j.brainres.2008.10.005

"... cognitive and motor ability impaired by CHRONIC cerebral hypoperfusion ..."
(emph. added j.t.)

--------------------------------------

53.
Cerebral perfusion changes in CHRONIC subdural hematoma
Philipp Jorg Slotty et al.
J Neurotrauma. 2013 Mar 1;30(5):347-51
DOI: 10.1089/neu.2012.2644

"... Neurologic deficits are likely induced by borderline perfusion ..."
(emph. added j.t.)

--------------------------------------

54.
... white matter injury in aged rats subjected to CHRONIC cerebral hypoperfusion
By: Amanda Santiago et al.
Neuropharmacology. 2018 Aug;138:360-370
DOI: 10.1016/j.neuropharm.2018.06.019

"CHRONIC cerebral hypoperfusion has been associated with aging-related vascular dementia, including Alzheimer's disease ..."
(emph. added j.t.)

--------------------------------------

55.
Molecular Mechanisms of Vascular Dementia: What Can Be Learned from Animal Models of CRONIC Cerebral Hypoperfusion?
By: Si-Qi Du et al.
Mol Neurobiol. 2017 Jul;54(5):3670-3682
DOI: 10.1007/s12035-016-9915-1

"... Numerous studies have demonstrated that CRONIC cerebral hypoperfusion is associated with the initiation and progression of vascular dementia and Alzheimer's disease ..."
(emph. added j.t.)

Back ↑

--------------------------------------

56.
CRONIC cerebral hypoperfusion: a key mechanism leading to vascular cognitive impairment and dementia ...
By: Jessica Duncombe et al.
Clin Sci (Lond). 2017 Sep 28;131(19):2451-2468
DOI: 10.1042/CS20160727 Print 2017 Oct 1

"Increasing evidence suggests that vascular risk factors contribute to neurodegeneration, cognitive impairment and dementia ..."
(emph. added j.t.)

--------------------------------------

57.
... Cerebral CRONIC Hypoperfusion ...
By: Jing Huang et al.
Biomed Res Int. 2018 Feb 26;2018:2321797
DOI: 10.1155/2018/2321797

"... dysfunction due to cerebral chronic hypoperfusion contributed to white matter lesion ..."
(emph. added j.t.)

--------------------------------------

58.
... learning impairments in CRONIC cerebral hypoperfusion ...
By: C Yang et al.
Transl Psychiatry. 2017 Jul 18;7(7):e1174
DOI: 10.1038/tp.2017.121

"CRONIC cerebral hypoperfusion is a major factor contributing to neurological disorders and cognitive decline ..."
(emph. added j.t.)

--------------------------------------

59.
... Cognitive Dysfunction following CHRONIC Cerebral Hypoperfusion
By: Zhao-Hui Yao et al.
Curr Neurovasc Res.2017;14(4):385-396
DOI: 10.2174/1567202614666171101115308

"CHRONIC Cerebral Hypoperfusion is an important vascular risk factor for vascular-related dementia cognitive impairment ..."
(emph. added j.t.)

--------------------------------------

60.
CHRONIC cerebral hypoperfusion induces long-lasting cognitive deficits accompanied by long-term hippocampal silent synapses increase in rats
By: Zhiqiang Wang et al.
Behav Brain Res. 2016 Mar 15;301:243-52
DOI: 10.1016/j.bbr.2015.12.047

"... cognitive deficits induced by CHRONIC cerebral hypoperfusion ..."
(emph. added j.t.)

Back ↑

--------------------------------------

61.
... Cognition Dysfunction and Synaptic Plasticity after CHRONIC Cerebral Hypoperfusion
By: Zhao-Hui Yao et al.
Neural Plast. 2019 Feb 24;2019:2158285
DOI: 10.1155/2019/2158285

"CHRONIC cerebral hypoperfusion is a common pathophysiological mechanism that underlies cognitive decline and degenerative processes in dementia and other neurodegenerative diseases ..."
(emph. added j.t.)

--------------------------------------

62.
... Cognition Dysfunction and Synaptic Plasticity after CHRONIC Cerebral Hypoperfusion
By: Zhao-Hui Yao et al.
Neural Plast. 2019 Feb 24;2019:2158285
DOI: 10.1155/2019/2158285

"CHRONIC cerebral hypoperfusion is a common pathophysiological mechanism that underlies cognitive decline and degenerative processes in dementia and other neurodegenerative diseases ..."
(emph. added j.t.)

--------------------------------------

63.
CHRONIC cerebral hypoperfusion inhibits calcium-induced long-term potentiation in rats
By: L H Sekhon et al.
Stroke. 1997 May;28(5):1043-7; discussion 1047-8
DOI: 10.1161/01.str.28.5.1043

"... cellular alteration caused by chronic cerebral hypoperfusion ... changes induced in neuronal function by CHRONIC noninfarctional reductions in cerebral blood flow ..."
(emph. added j.t.)

--------------------------------------

64.
... CHRONIC cerebral hypoperfusion-induced hippocampal neuronal damage ...
By: Da-Peng Wang et al.
Acta Histochem. 2020 Apr;122(3):151514
DOI : 10.1016/j.acthis.2020.151514

"... CHRONIC cerebral hypoperfusion -induced neuronal damage ..."
(emph. added j.t.)

--------------------------------------

65.
CHRONIC cerebral hypoperfusion enhances Tau hyperphosphorylation and reduces autophagy in Alzheimer's disease mice
By: Lifeng Qiu et al.
Sci Rep. 2016 Apr 6;6:23964
DOI: 10.1038/srep23964

"Cerebral hypoperfusion ... [have] been identified as being associated with the development of Alzheimer's disease ..."
(emph. added j.t.)

Back ↑

--------------------------------------

66.
... neuronal damage in a rat model of CHRONIC cerebral hypoperfusion
By: Tomohisa Yamamoto et al.
J Anesth. 2018 Apr;32(2):182-188
DOI: 10.1007/s00540-018-2458-z

"... cognitive dysfunction is likely to occur in elderly people, who often suffer from cerebral hypoperfusion ..."
(emph. added j.t.)

--------------------------------------

67.
Acceleration of NLRP3 inflammasome by CHRONIC cerebral hypoperfusion in Alzheimer's disease model mouse
By: Jingwei Shang et al.
Neurosci Res. 2019 Jun;143:61-70
DOI: 10.1016/j.neures.2018.06.002

"The present study demonstrated that CHRONIC cerebral hypoperfusion strongly enhanced primary Alzheimer's disease pathology including neuroinflammation, amyloid-beta accumulations and neurovascular unit dissociation in Alzheimer's disease ..."
(emph. added j.t.)

--------------------------------------

68.
CHRONIC cerebral hypoperfusion induced by bilateral carotid artery stenosis causes selective recognition impairment in adult mice
By: Arati Patel et al.
Neurol Res. 2017 Oct;39(10):910-917
DOI: 10.1080/01616412.2017.1355423

"CHRONIC cerebral hypoperfusion can result in vascular dementia and small vessel white matter ischemic* injury ..."

*Brain Ischemia
Cerebral ischemia is defined as a flow of blood to the brain that is
insufficient to meet its metabolic demands, leading to loss of function and CELL DEATH.
(emph. added j.t.)

--------------------------------------

69.
... cognitive impairment in a mouse CHRONIC cerebral hypoperfusion model
By: Masashi Kakae et al.
Biochem Biophys Res Commun.2019 Jul 5;514(4):1040-1044
DOI: 10.1016/j.bbrc.2019.05.055

"... cognitive impairment induced by CHRONIC cerebral hypoperfusion ..."
(emph. added j.t.)

--------------------------------------

70.
... Cognitive Impairment in CHRONIC Cerebral Hypoperfusion ...
By: Jihye Bang et al.
Nutrients. 2019 Nov 13;11(11):2755
DOI: 10.3390/nu11112755

"CHRONIC cerebral hypoperfusion causes cognitive impairment and neurogenic inflammation BY reducing blood flow ..."
(emph. added j.t.)

Back ↑

--------------------------------------

71.
... cognitive impairments after CHRONIC cerebral hypoperfusion in rats
By: Li-Ye Wang et al.
J Ethnopharmacol.2019 Jun 28;238:111846
DOI: 10.1016/j.jep.2019.111846

"... cognitive impairment induced by CHRONIC cerebral hypoperfusion ..."
(emph. added j.t.)

--------------------------------------

72.
CHRONIC Cerebral Hypoperfusion Induced Synaptic Proteome Changes in the rat Cerebral Cortex
By: Katalin Völgyi et al.
Mol Neurobiol. 2018 May;55(5):4253-4266
DOI: 10.1007/s12035-017-0641-0

"CHRONIC cerebral hypoperfusion evokes mild cognitive impairment and contributes to the progression of vascular dementia and Alzheimer's disease ..."
(emph. added j.t.)

--------------------------------------

73.
CHRONIC cerebral hypoperfusion alters amyloid-beta peptide pools leading to cerebral amyloid angiopathy, microinfarcts and haemorrhages in Tg-SwDI mice
By: Natalia Salvadores et al.
Clin Sci (Lond). 2017 Jul 24;131(16):2109-2123
DOI: 10.1042/CS20170962

"Cerebral hypoperfusion is an early feature of Alzheimer's disease that influences the progression from mild cognitive impairment to dementia ..."
(emph. added j.t.)

--------------------------------------

74.
From CHRONIC cerebral hypoperfusion to Alzheimer-like brain pathology and neurodegeneration
By: Yang Zhao et al.
Cell Mol Neurobiol. 2015 Jan;35(1):101-10
DOI: 10.1007/s10571-014-0127-9

"Recent studies have revealed an important role of CHRONIC cerebral hypoperfusion in neurodegeneration and dementia, including vascular dementia and Alzheimer's disease ..."
(emph. added j.t.)

--------------------------------------

75.
CHRONIC cerebral hypoperfusion-induced memory impairment and hippocampal long-term potentiation deficits ...
By: Thenmoly Damodaran et al.
Pharmacol Rep. 2019 Jun;71(3):443-448
DOI: 10.1016/j.pharep.2019.01.012

"... CHRONIC cerebral hypoperfusion induced cognitive deficits [and] could be an effective therapeutic target for the treatment of vascular dementia ..."
(emph. added j.t.)

Back ↑

--------------------------------------

76.
CHRONIC Cerebral Hypoperfusion Promotes Amyloid-Beta Pathogenesis ...
By: Zhiyou Cai et al.
Neurochem Res. 2017 Dec;42(12):3446-3455
DOI: 10.1007/s11064-017-2391-9

"... cerebral hypoperfusion which promotes amyloid-beta pathogenesis ..."
(emph. added j.t.)

--------------------------------------

77.
... CHRONIC Cerebral Hypoperfusion ...
By: Li-Juan Li et al.
Sichuan Da Xue Xue Bao Yi Xue Ban. 2020 Jul;51(4):480-487
DOI: 10.12182/20200760104

"... cognition deterioration induced by CHRONIC cerebral hypoperfusion ..."
(emph. added j.t.)

--------------------------------------

78.
CHRONIC cerebral hypoperfusion ...
By: Takuya Shimada et al.
Neurosci Lett. 2019 Jun 21;704:133-14
DOI: 10.1016/j.neulet.2019.04.009

"... increasing evidence has revealed that vascular risk factors influence the midlife development of Alzheimer's disease ..."
(emph. added j.t.)

--------------------------------------

79.
... CHRONIC cerebral hypoperfusion ...
By: Yu Takahashi et al.
Neuroreport. 2020 Jan 27;31(2):148-155
DOI: 10.1097/WNR.0000000000001391

"... CHRONIC cerebral hypoperfusion is associated with white matter lesions and risk of dementia ..."
(emph. added j.t.)

--------------------------------------

80.
CHRONIC Cerebral Hypoperfusion ... Complement Cascades in Alzheimer's Disease ...
By: Xiaowen Shi et al.
Neuroscience 2019 Sep 15;416:126-136
DOI: 10.1016/j.neuroscience.2019.07.050

"... Alzheimer's disease in the elderly is frequently accompanied by CHRONIC cerebral hypoperfusion ... and accelerates the Alzheimer's disease pathology ..."
(emph. added j.t.)

Back ↑

--------------------------------------

81.
... CHRONIC Cerebral Hypoperfusion ...
By: Dryelle L R Severiano et al.
Neuroscience 2020 Feb 1;426:1-12
DOI: 10.1016/j.neuroscience.2019.11.014

"... Vascular dementia is a major cognitive disorder originated from a blood flow disruption in the brain ..."
(emph. added j.t.)

--------------------------------------

82.
The effect of CHRONIC cerebral hypoperfusion on the pathology of Alzheimer's disease ..."
By: Jae-Hyung Park et al.
Sci Rep. 2019 Oct 1;9(1):14102
DOI: 10.1038/s41598-019-50681-4

"... CHRONIC cerebral hypoperfusion can induce Alzheimer's disease pathology and may play a significant role in Alzheimer's disease development ..."
(emph. added j.t.)

--------------------------------------

83.
... Cognitive Impairment Induced by CHRONIC Cerebral Hypoperfusion in Rats
By: Chen Fang et al.
Mol Neurobiol. 2017 Dec;54(10):8370-8385
DOI: 10.1007/s12035-016-0268-6

"... cognitive impairment induced by CHRONIC cerebral hypoperfusion ..."
(emph. added j.t.)

--------------------------------------

84.
... cognitive function in a rat model of CHRONIC cerebral hypoperfusion
By: Lei Zhang et al.
Pharmacol Biochem Behav. 2013 Feb;103(4):693-700
DOI: 10.1016/j.pbb.2012.12.023

"... cognitive impairments induced by CHRONIC cerebral hypoperfusion ..."
(emph. added j.t.)

--------------------------------------

84.1
The role of CHRONIC brain hypoperfusion in the pathogenesis of Alzheimer's disease--facts and hypotheses
By: Denes Zadori et al.
Ideggyogy Sz. 2007 Nov 30;60(11-12):428-37
PMID: 18198789

"... CHRONIC ... hypoperfusion ... and the resulting hypometabolism ... leads to the degeneration of capillaries in ... the watershed areas of the brain ... causing the deterioration of diffusion. The further reduction of nutrient and oxygen support of neurons is capable to INITIATE a neurodegenerative process ..."
(emph. added j.t.)

Back ↑

--------------------------------------

84.2
... hypoperfused brain ... primary target for the development of Alzheimer's disease
By: Ali Aliyev et al.
J Neurol Sci. 2005 Mar 15;229-230:285-92
DOI: 10.1016/j.jns.2004.11.040

"... The pathogenesis, which is primarily RESPONSIBLE for Alzheimer's disease ... seems to involve CHRONIC hypoperfusion ..."
(emph. added j.t.)

--------------------------------------

84.3
The impact of cerebrovascular aging on vascular cognitive impairment and dementia
By: Tuo Yang et al.
Ageing Res Rev. 2017 Mar
DOI: 10.1016/j.arr.2016.09.007

".... One of the major of types of cognitive dysfunction due to CHRONIC cerebral hypoperfusion is vascular cognitive impairment and dementia ..."
(emph. added j.t.)

--------------------------------------

84.4
The impact of cerebrovascular aging on vascular cognitive impairment and dementia
By: Tuo Yang et al.
Ageing Res Rev. 2017 Mar;34:15-29
DOI: 10.1016/j.arr.2016.09.00

"... One of the major of types of cognitive dysfunction due to CHRONIC cerebral hypoperfusion is vascular cognitive impairment and dementia ..."
(emph. added j.t.)

--------------------------------------

84.5
The pathological and clinical consequences of chronic cerebral hypoperfusion
By: S Horvath
Orv Hetil. 2001 Feb 18;142(7):323-9
PMID: 11243013

"... Cerebral hypoperfusion is verifiable in patients ... in diseases characterised by mild or serious cognitive impairment ... This review gives a summary of ... clinical consequences of CHRONIC cerebral hypoperfusion, and the role of that in evolution and persistence of cognitive disturbances ..."
(emph. added j.t.)

--------------------------------------

84.6
The role of chronic brain hypoperfusion in the pathogenesis of Alzheimer's disease--facts and hypotheses
By: Denes Zadori et al.
Ideggyogy Sz. 2007 Nov 30;60(11-12):428-37

"... cardiovascular risk factors can precipitate CHRONIC brain hypoperfusion ..."
(emph. addd j.t.)

Back ↑

--------------------------------------

84.7
Alzheimer's disease: cardiovascular risk factors must be assessed
By: Antoine et al.
Rev Med Interne. 2006 Jan;27(1):21-31
DOI: 10.1016/j.revmed.2005.04.037

"... alteration of arterial walls, inducing CHRONIC brain hypoperfusion, as the PRIMARY TRIGGER in the physiopathology of the [Alzheimer's] disease ..."
(emph. addd j.t.)

--------------------------------------

84.8
Chronic mild cerebrovascular dysfunction as a cause for Alzheimer's disease?
By: Christian Humpel
Exp Gerontol. 2011 Apr;46(4):225-32
DOI: 10.1016/j.exger.2010.11.032

"... This review proposes the hypothesis that a CHRONIC mild longlasting cerebrovascular dysfunction could INITIATE a cascade of events LEADING to Alzheimer's disease ..."
(emph. addd j.t.)

--------------------------------------

84.9
Is Alzheimer's disease a neurodegenerative or a vascular disorder? Data, dogma, and dialectics
By: Jack C de la Torre
Lancet Neurol. 2004 Mar;3(3):184-90
DOI: 10.1016/S1474-4422(04)00683-0

"... The consensus of these studies indicates that CHRONIC brain hypoperfusion is linked to Alzheimer's disease risk factors ..."
(emph. addd j.t.)

--------------------------------------

84.10
Oxiracetam can improve cognitive impairment after chronic cerebral hypoperfusion in rats
By: Xiao-Li Yao et al.
Psychiatry Res. 2016 Dec 30;246:284-292
DOI: 10.1016/j.psychres.2016.10.006

"Chronic cerebral hypoperfusion induces cognitive deficits ..."

--------------------------------------

84.11
Cardiac disorders and cognitive impairment in patients with CHRONIC cerebral ischemia
By: E G Semushkina et al.
Zh Nevrol Psikhiatr Im S S Korsakova. 2013;113(2):9-13

"... atherosclerosis of brain vessels ... predicted cognitive impairment in patients with chronic brain ischemia. Reduced left ventricular ejection fraction was the main cardiac factor DETERMINING THE SEVERITY of cognitive disturbances."
(emph. addd j.t.)
Back to: "where the condition becomes chronic"↑

--------------------------------------

85.
blood pressure reduction in hypertensive acute ischemic* stroke patients DOES NOT affect cerebral blood flow
By: Mahesh Kate et al.
J Cereb Blood Flow Metab. 2019 Sep.
DOI: 10.1177/0271678X18774708.

"Antihypertensive therapy, based on presenting blood pressure, in acute stroke patients WAS NOT associated with an increased volume of total [cerebral] hypoperfused tissue."

*Brain Ischemia
Cerebral ischemia is defined as a flow of blood to the brain that is
insufficient to meet its metabolic demands, leading to loss of function and CELL DEATH.
(emph. added j.t.)

--------------------------------------

86.
Treatment of dementia
By: K Blom et al.
Ned Tijdschr Geneeskd. 2017;161:D1851

"... Interventions towards cardiovascular risk factors DO NOT slow down cognitive decline ..."
(emph. added j.t.)

--------------------------------------

87.
Vascular risk factors for incident Alzheimer's disease and vascular dementia ...
By: Kathleen M Hayden et al.
Alzheimer Dis Assoc Disord. Apr-Jun 2006;20(2):93-100
DOI: 10.1097/01.wad.0000213814.43047.86

"... NO ASSOCIATION between ... history of HYPERTENSION and high cholesterol and ALZHEIMER'S DISEASE ..."
(emph. added j.t.)

--------------------------------------

88.
Heart diseases and long-term risk of dementia and Alzheimer's disease ...
By: Minna Rusanen et al. J Alzheimers Dis. 2014;42(1):183-91.
DOI: 10.3233/JAD-132363

"... atrial fibrillation in late-life was an INDEPENDENT RISK FACTOR FOR DEMENTIA ..."
(emph. added j.t.)

--------------------------------------

88.1
Atherosclerosis, Hypertension, and Diabetes in Alzheimer's Disease, Vascular Dementia, and Mixed Dementia: Prevalence and Presentation
By: Javanshiri, Keivan et al.
Journal of Alzheimer's Disease, vol. 65, no. 4, pp. 1247-1258, 2018
DOI: 10.3233/JAD-180644

"Alzheimer's disease exhibit such different profiles of .... hypertension ... that clearly point toward DIFFERENT PATHOGENIC origin with LOW LIKELIHOOD OF SHARED RISK factors."
(emph. added j.t.)

--------------------------------------

88.2
Blood pressure lowering in patients without prior cerebrovascular disease for prevention of cognitive impairment and dementia
By: Bernadette McGuinness et al.
Cochrane Database Syst Rev. 2009 Oct 7;2009(4):CD004034
DOI: 10.1002/14651858.CD004034.pub3

"... There is NO CONVINCING EVIDENCE from the trials identified that blood pressure lowering in late-life PREVENTS the development of dementia or cognitive impairment ..."
(emph. added j.t.)

--------------------------------------

88.3
Are cognitive function and blood pressure related?
By: M Viitanen et al.
Drugs Aging. 1997 Sep;11(3):165-9
DOI:10.2165/00002512-199711030-00001

"... The relationship between blood pressure and cognition may be MORE COMPLICATED ..."
(emph. added j.t.)

Back to: "blood pressure is not necessarily indicative of cerebral blood"↑

--------------------------------------

89.
"About 1 in 4 seniors age 85+ have been diagnosed with dementia"

The Canadian Institute for Health Information (CIHI)
https://www.cihi.ca/en/about-cihi

--------------------------------------

89.1
Periodontal disease's contribution to Alzheimer's disease progression in Down syndrome
By: Angela R. Kamer et al.
Alzheimer's & Dementia: Volume 2, Issue 1 p. 49-57
DOI: 10.1016/j.dadm.2016.01.001

... Eleven percent of people older than 65 and 33% of those >85 have Alzheimer's disease ...

--------------------------------------

89.2
"The percentage of people with Alzheimer's dementia increases with age: 5.3% of people age 65 to 74, 13.8% of people age 75 to 84, and 34.6% of people age 85."

2021 Alzheimer's disease facts and figures
DOI/10.1002/alz.12328

Back to: "eventually, end up with dementia"↑

--------------------------------------

90
Neuropsychology of cognitive ageing, minimal cognitive impairment, Alzheimer's disease, and vascular cognitive impairment
By: Jaap Lindeboom et al.
Eur J Pharmacol. 2004 Apr 19;490(1-3):83-6
DOI: 10.1016/j.ejphar.2004.02.046

"... It may be concluded that cognitive decline IS NOT an inevitable outcome of ageing ..."
(emph. added j.t.)

--------------------------------------

90.1
Vascular contributions to cognitive impairment and dementia including Alzheimer's disease
By: Heather M Snyder et al.
Alzheimers Dement.2015 Jun;11(6):710-7
DOI: 10.1016/j.jalz.2014.10.008

"... Recent research has yielded evidence that the borders between development [of neurodegenerative disease] and AGING sometimes can be FUZZY ... factors known to affect brain and cognition in aging will often do so through a LIFE-LONG accumulation of impact, and DOES NOT need to be specific to aging ... LIFESPAN rather than aging, and multidimensional systems-vulnerability rather than simple "hypothetical biomarker" model of age-associated cognitive decline and dementia ..."
(emph. added j.t.)

--------------------------------------

90.2
Predicting Factors in Identifying Cognitive Decline among Thai Adults
By: Jongiate Youngsakul et al.
J Med Assoc Thai. 2017 Mar.

"... The incidence of cognitive decline among Thai WORKING AGED ADULT was 8.1% ...
The AVERAGE AGE of subjects was 42.93±10.8 years (RANGE 21 TO 61 YEARS) ..."
(emph. added j.t.)

--------------------------------------

90.3
The importance of cognitive aging for understanding dementia
By: Archana Singh-Manoux et al.
Age (Dordr). 2010 Dec;32(4):509-12
DOI: 10.1007/s11357-010-9147-7

"... decline in various cognitive functions FROM ADULTHOOD to old age ...
dementia assessed ... STARTING EARLIER in the life ..."
(emph. added j.t.)

--------------------------------------

90.4
Gene Therapy, A Novel Therapeutic Tool for Neurological Disorders: Current Progress, Challenges and Future Prospective
By: Ashif Iqubal et al.
Curr Gene Ther. 2020;20(3):184-194
DOI: 10.2174/1566523220999200716111502

"... ALL AGED POPULATIONS are susceptible to one or other neurological problems with symptoms of ... neurodegeneration and cognitive dysfunction ..."
(emph. added j.t.)

Back to: "study should comprise subjects of all age groups"↑

--------------------------------------

91.
Cerebral blood flow changes during aging process and in cognitive disorders: A review
By: Naghmeh Mokhber et al.
Neuroradiol J. 2021 Aug.
DOI: 10.1177/19714009211002778

"... There is promising evidence regarding the utility of cerebral blood flow studies in cognition research ..."

--------------------------------------

91.1
Vascular cognitive impairment, dementia, aging and energy demand. A vicious cycle
By: A Popa-Wagner et al.
J Neural Transm (Vienna)2015 Aug;122 Suppl 1:S47-54
DOI: 10.1007/s00702-013-1129-3

"... cognitive health depends on cerebrovascular health ..."

--------------------------------------

91.2
Functional vascular contributions to cognitive impairment and dementia: mechanisms and consequences of cerebral autoregulatory dysfunction, endothelial impairment, and neurovascular uncoupling in aging
By: Peter Toth et al.
Am J Physiol Heart Circ Physiol. 2017
DOI: 10.1152/ajpheart.00581.2016

"... MAINTENANCE of cerebral perfusion ... [is a] prerequisite[s] for the prevention of cerebral ischemia* and neuronal dysfunction ..."

*Brain Ischemia
Cerebral ischemia is defined as a flow of blood to the brain that is insufficient to meet its metabolic demands, leading to loss of function and CELL DEATH.
(emph. added j.t.)

--------------------------------------

91.3
...neurovascular coupling responses and cognitive performance ...
By: Stefano Tarantini et al.
Geroscience. 2019 Oct.
DOI: 10.1007/s11357-019-00101-2

"... Adjustment of cerebral blood flow ... plays an IMPORTANT role in the MAINTENANCE of healthy cognitive function ..."
(emph. added j.t.)

Back to: "would brain-blood-flow to be of any use?"↑

--------------------------------------

92.
Functional vascular contributions to cognitive impairment and dementia: mechanisms and consequences of cerebral autoregulatory dysfunction, endothelial impairment, and neurovascular uncoupling in aging
By: Peter Toth et al.
Am J Physiol Heart Circ Physiol. 2017
DOI: 10.1152/ajpheart.00581.2016

"... MAINTENANCE of cerebral perfusion ... [is a] prerequisite[s] for the prevention of cerebral ischemia* and neuronal dysfunction ..."

*Brain Ischemia
Cerebral ischemia is defined as a flow of blood to the brain that is insufficient to meet its metabolic demands, leading to loss of function and CELL DEATH.
(emph. added j.t.)

--------------------------------------

92.1
Cerebral blood flow measured by arterial spin labeling MRI as a preclinical marker of Alzheimer's disease
By: Christina E Wierenga et al.
J Alzheimers Dis. 2014
DOI: 10.3233/JAD-141467

"... MEASUREMENT of cerebral blood flow as a possible biomarker of Alzheimer's disease ..."
(emph. added j.t.)

--------------------------------------

92.2
Alzheimer's disease, cerebrovascular disease ...
By: Kie Honjo et al.
Can J Neurol Sci. 2012 Nov;39(6):712-28
DOI: 10.1017/s0317167100015547

"... vascular risk factor MANAGEMENT may be important for Alzheimer's disease prevention and treatment."
(emph. added j.t.)

--------------------------------------

92.3
A brain stress test: Cerebral perfusion during memory encoding in mild cognitive impairment
By: Long Xie et al.
Neuroimage Clin. 2016
DOI: 10.1016/j.nicl.2016.03.002

"... growing body of literature suggests that regional cerebral blood flow is ALTERED in neurodegenerative diseases ...
(emph. added j.t.)

--------------------------------------

92.4
Cerebrovascular Hemodynamics on Transcranial Doppler Ultrasonography and Cognitive Decline in Mild Cognitive Impairment
By: Eun-Ye Lim et al.
J Alzheimers Dis. 2018
DOI: 10.3233/JAD-180026

"... hemodynamic changes ... and cognitive decline ... PREDICTING mild cognitive impairment patients who will PROGRESS to Alzheimer's disease ..."
(emph. added j.t.)

--------------------------------------

92.5
Basal and hypercapnia-altered cerebrovascular perfusion PREDICT mild cognitive impairment in aging rodents
By: M Mitschelen et al.
neuroscience 2009
DOI: 10.1016 j.neuroscience.2009.08.070

... Our results indicate that age-related changes in vascular reactivity and perfusion are IMPORTANT CONTRIBUTING FACTORS in memory impairment ..."
(emph. added j.t.)
Back ↑

--------------------------------------

92.6
Vascular cognitive impairment, dementia, aging and energy demand. A vicious cycle
By: A Popa-Wagner et al.
J Neural Transm (Vienna). 2015 Aug.
DOI: 10.1007/s00702-013-1129-3

"To a great extent, cognitive health DEPENDS on cerebrovascular health ..."
(emph. added j.t.)

--------------------------------------

92.7
On the normalization of cerebral blood flow
By: Romain Guibert et al.
J Cereb Blood Flow Metab. 2013 May;33(5):669-72
DOI: 10.1038/jcbfm.2013.39

"... Cerebral blood flow is the MOST COMMON PARAMETER for the quantification of brain's function ..."
(emph. added j.t.)

--------------------------------------

92.8
Clinically asymptomatic vascular brain injury: a potent cause of cognitive impairment among older individuals
By: Charles DeCarli
J Alzheimers Dis. 2013;33 Suppl 1(0 1):S417-26
DOI: 10.3233/JAD-2012-129004

"... the impact of cerebrovascular risk factors on brain injury appears to BEGIN IN MIDDLE life and additively increases the likelihood of later life dementia ... Results of this review emphasize the NEED FOR EARLY DETECTION and treatment of vascular risk factors to improve the cognitive health of our rapidly aging population ..."
(emph. added j.t.)

--------------------------------------

92.9
Midlife interventions are critical in prevention, delay, or improvement of Alzheimer's disease and vascular cognitive impairment and dementia
By: Sam Gandy et al.
F1000Res. 2017 Apr 3;6:413
DOI: 10.12688/f1000research.11140.1. eCollection 2017

"... Effective prevention therefore MAY NEED TO BEGIN in midlife in order to succeed ..."
(emph. added j.t.)

--------------------------------------

92.10
At the Heart of Brain Disorders - Preventing Cognitive Decline and Dementia
By: Augusto Vicario et al.
Eur Cardiol. 2015 Jul;10(1):60-63
DOI: 10.15420/ecr.2015.10.01.60

"... EARLY DETECTION and control of modifiable vascular risk factors seem to be THE ONLY CURRENT STRATEGIES to prevent cognitive impairment and dementia ..."
(emph. added j.t.)

Back to: "routine monitoring of blood-flow to the brain"↑

--------------------------------------

93.
Longitudinal Cerebral Blood Flow Changes in Normal Aging and the Alzheimer's Disease Continuum Identified by Arterial Spin Labeling MRI
By: Aldo Camargo et al.
J Alzheimers Dis. 2021
DOI: 10.3233/JAD-210116

"... studies have shown LOWER cerebral blood flow in Alzheimer's disease ..."
(emph. added j.t.)

--------------------------------------

94.
Cortical microinfarcts in memory clinic patients are associated with reduced cerebral PERFUSION
By: Doeschka A Ferro et al.
J Cereb Blood Flow Metab. 2020 Sep.
DOI: 10.1177/0271678X19877403

"Cerebral cortical microinfarcts are small ischemic* lesions ASSOCIATED with cognitive impairment and dementia."

*Brain Ischemia
Cerebral ischemia is defined as a flow of blood to the brain that is
insufficient to meet its metabolic demands, leading to loss of function and CELL DEATH.
(emph. added j.t.)

--------------------------------------

95.
Cerebral blood flow measured by arterial spin labeling MRI as a preclinical marker of Alzheimer's disease
By: Christina E Wierenga et al.
J Alzheimers Dis. 2014
DOI: 10.3233/JAD-141467

"There is growing recognition that cerebral hypoperfusion is RELATED to the pathogenesis of Alzheimer's disease ..."
(emph. added j.t.)

--------------------------------------

96.
... cerebral blood flow in a cohort of middle-aged adults
By: Martine Elbejjani et al.
J Cereb Blood Flow Metab. 2019 Jul.
DOI: 10.1177/0271678X18754973

"... [dementia] is thought to be MEDIATED by hypoperfusion ..."
(emph. added j.t.)

--------------------------------------

96.1
Cerebral blood flow in normal aging adults: cardiovascular determinants, clinical implications, and aerobic fitness
By: Takashi Tarumi et al.
J Neurochem. 2018 Mar.
DOI: 10.1111/jnc.14234. Epub 2017 Nov 7

"... The brain is the most metabolically active organ with limited intracellular energy storage and CRITICALLY DEPENDS on cerebral blood flow ..."
(emph. added j.t.)

--------------------------------------

96.2
Cerebrovascular Hemodynamics on Transcranial Doppler Ultrasonography and Cognitive Decline in Mild Cognitive Impairment
By: Eun-Ye Lim et al.
J Alzheimers Dis. 2018
DOI: 10.3233/JAD-180026

"... neurovascular dysfunction may be CLOSELY RELATED to cognitive impairment and dementia ... there is a CLOSE ASSOCIATION between ... hemodynamic changes ... and cognitive decline ..."
(emph. added j.t.)
Back ↑

--------------------------------------

96.3
Differential regional cerebral blood flow reactivity to alterations in end-tidal gases in healthy volunteers
By: W Alan C Mutch et al.
Can J Anaesth. 2021 Oct.
DOI: 10.1007/s12630-021-02042-x

"... Altered regional cerebrovascular reactivity is LINKED to neurologic dysfunction ...
(emph. added j.t.)

--------------------------------------

96.4
Small vessel disease and the resting functional architecture of the brain
By: Robert D Stevens et al.
J Cereb Blood Flow Metab.2014 Jul;34(7):1089-90
DOI: 10.1038/jcbfm.2014.69

"... Small vessel disease is LINKED to cognitive impairment and dementia ..."
(emph. added j.t.)

--------------------------------------

96.5
Vascular contributions to cognitive impairment and dementia including Alzheimer's disease
By: Heather M Snyder et al.
Alzheimers Dement.2015 Jun;11(6):710-7
DOI: 10.1016/j.jalz.2014.10.008

"... Scientific evidence continues to demonstrate the LINKAGE of vascular contributions to cognitive impairment and dementia such as Alzheimer's disease ..."
(emph. added j.t.)

--------------------------------------

96.6
Primary cerebral blood flow deficiency and Alzheimer's disease: shadows and lights
By: Marianna Mazza et al.
J Alzheimers Dis. 2011;23(3):375-89
DOI: 10.3233/JAD-2010-090700

"... reduced perfusion have on the final development of Alzheimer's disease ..."

--------------------------------------

96.7
Cerebral Perfusion and the Burden of Small Vessel Disease in Patients Referred to a Memory Clinic
By: Laurien Onkenhout et al.
Cerebrovasc Dis. 2020;49(5):481-486
DOI: 10.1159/000510969

"... It has been suggested that cerebral hypoperfusion IS INVOLVED in the etiology of these [small vessel disease] lesions ..."
(emph. added j.t.)
Back ↑

--------------------------------------

96.8
Cerebral blood flow regulation and neurovascular dysfunction in Alzheimer disease
By: Kassandra Kisler et al.
Nat Rev Neurosci. 2017 Jul;18(7):419-434
DOI: 10.1038/nrn.2017.48

"... neurovascular dysfunction in neurodegenerative disorders such as Alzheimer disease ..."

--------------------------------------

96.9
Pattern of and risk factors for brain microbleeds in neurodegenerative dementia
By: Javier Olazar et al.
Am J Alzheimers Dis Other Demen. 2014 May;29(3):263-9
DOI: 10.1177/1533317513517043

"... Brain microbleeds are associated with vascular burden and Alzheimer's Disease diagnosis in old patients with neurodegenerative dementia ..."

--------------------------------------

96.10
Ageing, neurodegeneration and brain rejuvenation
By: Tony Wyss-Coray
Nature. 2016 Nov 10;539(7628):180-186
DOI: 10.1038/nature20411

"... neurodegeneration and dementia ... encoded partly in a blood-based signature ..."

--------------------------------------

96.11
The close link between brain vascular pathological conditions and neurodegenerative diseases: Focus on some examples and potential treatments
By: Giuseppe Schiro et al.
Vascul Pharmacol. 2022 Feb;142:106951
DOI: 10.1016/j.vph.2021.106951

"... reduced cerebral blood flow ... have been [also] demonstrated to contribute to neurodegenerative diseases ... [and] have been documented to be significantly ASSOCIATED with the onset of the cognitive impairment ..."
(emph. added j.t.)

--------------------------------------

96.12
The progression of cognitive deterioration and regional cerebral blood flow patterns in Alzheimer's disease: a longitudinal SPECT study
By: Haruo Hanyu et al.
J Neurol Sci. 2010 Mar 15;290(1-2):96-101.
DOI: 10.1016/j.jns.2009.10.022

"... Our study suggests a significant ASSOCIATION between regional cerebral blood flow deficits and rapid cognitive deterioration ..."
(emph. added j.t.)
Back ↑

--------------------------------------

96.13
Neuropsychology of cognitive ageing, minimal cognitive impairment, Alzheimer's disease, and vascular cognitive impairment
By: Jaap Lindeboom et al.
Eur J Pharmacol. 2004 Apr 19;490(1-3):83-6
DOI: 10.1016/j.ejphar.2004.02.046

"... Cerebrovascular disease plays an IMPORTANT ROLE in forms of cognitive decline ..."
(emph. added j.t.)

--------------------------------------

96.14
Intracranial atherosclerosis as a contributing factor to Alzheimer's disease dementia
By: Alex E Roher et al.
PMID: 21388893 PMCID: PMC3117084
DOI: 10.1016/j.jalz.2010.08.228

"... substantial body of evidence ... STRONGLY ASSOCIATES atherosclerotic vascular disease with Alzheimer's disease ..."
(emph. added j.t.)

--------------------------------------

96.15
Associations Between Midlife Vascular Risk Factors and 25-Year Incident Dementia in the Atherosclerosis Risk in Communities Cohort
By: Rebecca F Gottesman et al.
JAMA Neurol. 2017 Oct 1;74(10):1246-1254
DOI: 10.1001/jamaneurol.2017.1658

"... Vascular risk factors have been associated with cognitive decline. MIDLIFE EXPOSURE to these factors may be MOST IMPORTANT in conferring late-life risk of cognitive impairment ..."
(emph. added j.t.)

--------------------------------------

96.16
The effects of hypertension on the cerebral circulation
By : Paulo W Pires et al.
Am J Physiol Heart Circ Physiol actions 2013 Jun 15;304(12):H1598-614
DOI: 10.1152/ajpheart.00490.2012

"... DEFICITS in cerebral blood flow are LINKED to cognitive decline ..."
(emph. added j.t.)

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96.17
Impact of multisession 40Hz tACS on hippocampal perfusion in patients with Alzheimer's disease

96.17
By: Giulia Sprugnoli et al.
Alzheimers Res Ther. 2021 Dec 20;13(1):203
DOI: 10.1186/s13195-021-00922-4

"Alzheimer's disease is ASSOCIATED with alterations in cortical PERFUSION that correlate with cognitive impairment."
(emph. added j.t.)

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96.18
Vascular dementia, hypertension, and the brain
By: C G Lis et al.
Neurol Res. 1997 Oct;19(5):471-80
DOI: 10.1080/01616412.1997.11740844

"... Alzheimer's disease with vascular components are becoming INCREASINGLY RECOGNIZED ..."
(emph. added j.t.)

Back to: "cerebral hypo-perfusion is associated"↑

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97.
Vascular cognitive impairment, dementia, aging and energy demand. A vicious cycle
By: A Popa-Wagner et al.
J Neural Transm (Vienna)
2015 Aug;122 Suppl 1:S47-54
DOI: 10.1007/s00702-013-1129-3

"... Understanding how vascular and metabolic factors interfere with progressive loss of functional neuronal networks becomes essential to DEVELOP EFFICIENT DRUGS TO PREVENT cognitive decline in elderly ..."
(emph. added j.t.)

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97.1
Cerebral blood flow in normal aging adults: cardiovascular determinants, clinical implications, and aerobic fitness
By: Takashi Tarumi et al.
Neurochem. 2018 Mar.
DOI: 10.1111/jnc.14234. Epub 2017 Nov 7

"... Currently, Alzheimer's disease lacks effective treatments; therefore, the DEVELOPMENT OF PREVENTIVE STRATEGY is urgently needed ..."
(emph. added j.t.)

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97.2
A possible role of atrial fibrillation as a risk factor for dementia
By: E Ettorre et al.
Arch Gerontol Geriatr. 2009;49 Suppl 1:71-6.
DOI: 10.1016/j.archger.2009.09.014

"... response in patients with Alzheimer's disease to therapy that improves cerebral blood flow is a CONSISTENT finding ..."
(emph. added j.t.)

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97.3
Alzheimer's disease: cardiovascular risk factors must be assessed
By: Antoine et al.
Rev Med Interne. 2006 Jan;27(1):21-31
DOI: 10.1016/j.revmed.2005.04.037

"... pharmacological interventions aimed on the PREVENTION of cognitive decline or the curative treatment for [Alzheimer's] disease ..."
(emph. added j.t.)

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97.4
Normal aging and cognition: the UNACKNOWLEDGED contribution of CEREBROVASCULAR risk factors
By: L Morra et al.
Neuropsychol Dev Cogn B Aging Neuropsychol Cogn. 2013;20(3):271-97
DOI: 10.1080/13825585.2012.693905

"Despite the widespread assumption that cognitive decline is an inherent part of the normal aging process, research suggests that part of the variance in age-related cognitive decline is attributable to MODIFIABLE FACTORS common in geriatric populations such as cerebrovascular risk factors."
(emph. added j.t.)

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97.5
Morning exercise mitigates the impact of prolonged sitting on cerebral blood flow in older adults
By: Michael J Wheeler et al.
J Appl Physiol (1985). 2019 Apr 1;126(4):1049-1055
DOI: 10.1152/japplphysiol.00001.201.2019

"PREVENTING DECLINES in cerebral blood flow is important for maintaining optimal brain health with aging."
(emph. added j.t.)

Back to: "would allow for a timely clinical/pharmacological intervention to take place"↑

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98.
Living beyond our physiological means: small vessel disease of the brain is an expression of a systemic failure in arteriolar function: a unifying hypothesis
By: Charlie S Thompson et al.
Stroke 2009 May;40(5):e322-30
DOI: 10.1161/STROKEAHA.108.542266

"... control of vascular risk factors ... may significantly REDUCE morbidity, mortality, and healthcare COSTS ..."
(emph. added j.t.)

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99
Living beyond our physiological means: small vessel disease of the brain is an expression of a systemic failure in arteriolar function: a unifying hypothesis
By: Charlie S Thompson et al.
Stroke 2009 May;40(5):e322-30
DOI: 10.1161/STROKEAHA.108.542266

"... control of vascular risk factors ... may significantly REDUCE ... healthcare COSTS ..."
(emph. added j.t.)

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99.1
Healthy Aging and Dementia: Two Roads Diverging in Midlife?
By: Katie Irwin et al.
Front Aging Neurosci. 2018 Sep 19;10:275
DOI: 10.3389/fnagi.2018.00275

"... By 2050, the number of people living with dementia worldwide could almost triple, from 47 to 132 million, WITH ASSOCIATED COSTS rising to $3 trillion ..."
(emph. added j.t.)

Back to: "Total costs of care for people with Dementia"↑

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100
The heart-brain connection: a multidisciplinary approach targeting a missing link in the pathophysiology of vascular cognitive impairment
By: Mark A van Buchem et al.
J Alzheimers Dis. 2014;42 Suppl 4:S443-51
DOI: 10.3233/JAD-141542

"... Recent data indicate that autoregulation of cerebral flow CANNOT always protect the brain from hypoperfusion ..."
(emph. added j.t.)

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100.1
The close link between brain vascular pathological conditions and neurodegenerative diseases: Focus on some examples and potential treatments
By: Giuseppe Schiro et al.
Vascul Pharmacol. 2022 Feb;142:106951.
DOI: 10.1016/j.vph.2021.106951

"... vascular alterations are also observed in cognitively unimpaired subjects ..."

Back to: "condition prevalence in the general population"↑

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101
The clinical manifestations and pathophysiology of cerebral small vessel disease
By: Ai-Juan Zhang et al.
Neurosci Bull 2010 Jun;26(3):257-64
DOI: 10.1007/s12264-010-1210-y

"... more attention should be paid to the importance of EARLY diagnosis and prophylactic treatment of small vessel disease ..."
(emph. added j.t.)

Back to: "It would allow for a timely"↑

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102
Cognitive decline before the age of 50 can be detected with sensitive cognitive measures
By: Daniel Ferreira et al.
Psicothema. 2015;27(3):216-22
DOI: 10.7334/psicothema2014.192

".. Our findings suggest subtle executive dysfunction BEFORE the age of 50 ...
... This profile could be explained by CHANGES ... starting AT MIDDLE-AGE ..."
(emph. added j.t.)

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102.1
New concepts of pathogenesis, diagnosis, and treatment of neurodegenerative diseases
By: M V Ugriumov
Vestn Ross Akad Med Nauk. 2010
PMID: 20919532

"... Over the INITIAL twenty-thirty years, chronic neurodegenerative diseases are developed as a PRECLINICAL condition, and their first symptoms appear only AFTER degeneration of a greater part of specific neurons ..."
(emph. added j.t.)

Back to: "in all other age groups"↑

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103
Is dementia a disease?
By: Fred C C Peng
Gerontology. Nov-Dec 2003;49(6):384-91
DOI: 10.1159/000073767

"It is concluded that dementia is NOT a disease."
(emph. added j.t.)

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104
Is dementia a disease?
By: Fred C C Peng
Gerontology. Nov-Dec 2003;49(6):384-91
DOI: 10.1159/000073767

"... Alzheimer's disease is now regarded by some as a vascular disorder with neurodegenerative consequence ..."

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105
The links between complex coronary disease, cerebrovascular disease, and degenerative brain disease
By: Jason C Kovacic et al.
Ann N Y Acad Sci. 2012 Apr;1254:99-105
DOI: 10.1111/j.1749-6632.2012.06482.x

"... cardiovascular disease has recently been implicated as playing a MAJOR ROLE in dementia ..."
(emph. added j.t.)

Back to: "treating the affliction as a disease in need of a cure."↑

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106
Alzheimer's disease drug development: translational neuroscience strategies
By: Jeffrey L Cummings et al.
CNS Spectr. 2013 Jun;18(3):128-38.
DOI: 10.1017/S1092852913000023

"Alzheimer's disease ... All phase 3 drug development programs for disease-modifying agents HAVE FAILED thus far ..."
(emph. added j.t.)

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107
Gene Therapy, A Novel Therapeutic Tool for Neurological Disorders: Current Progress, Challenges and Future Prospective
By: Ashif Iqubal et al. Curr Gene Ther. 2020;20(3):184-194
DOI: 10.2174/1566523220999200716111502

"... At present, available PHARMACOTHERAPEUTICS ARE INSUFFICIENT to treat these diseased conditions [Neurological disorders] and in most cases, they provide only palliative effect ..."
(emph. added j.t.)

Back to: "have failed with no exception."↑

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108
Midlife interventions are critical in prevention, delay, or improvement of Alzheimer's disease and vascular cognitive impairment and dementia
By: Sam Gandy et al.
F1000Res. 2017 Apr 3;6:413
DOI: 10.12688/f1000research.11140.1. eCollection 2017

"... BILLIONS OF DOLLARS later, all efforts at disease-modifying interventions [of dementias] have failed ..."
(emph. added j.t.)

Back to: "well-supported."↑

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109
Midlife interventions are critical in prevention, delay, or improvement of Alzheimer's disease and vascular cognitive impairment and dementia
By: Sam Gandy et al.
F1000Res. 2017 Apr 3;6:413
DOI: 10.12688/f1000research.11140.1 eCollection 2017

"... none of the world's economies CAN SUSTAIN THE COSTS of caring for this epidemic of brain failure that is devastating HALF of the over 85-year-olds globally ..."
(emph. added j.t.)

Back to: "questionable at best."↑