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

--- 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].

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

It is prudent, therefore, to step back and review the efforts to concur dementia from its historical prospective 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 bearing his name (widely accepted and known as the 'amyloid hypothesis'; yet, lately seriously questioned as of its validity [1 to 8.2]).

Well into the second century since then, despite a continuos extensive and well-supported research of these elements, Alzheimer's disease, and dementia in general, still can't be cured, prevented, or even slowed down [9 and 10].

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. All the efforts to find this elusive cure have failed with no exception.

This begs examination of the question:

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

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

Ample supporting data already available from a good number of independent studies suggesting that cerebral hypo-perfusion is a possible root cause of dementia [12 to 27]. However, it's incumbent on the research sphere to generate the required experimental data and to provide a direct study proof of this condition prevalence in the general population.

The proposed study sould comprise adult subjects, way younger than the elderly [28 to 28.3]. Certain percentage of those are likely to show brain-blood-flow which, usually, expected in dementia cases regardless of subject age or health condition [29]. This percentage, conceivably, will agree with the percentage of dementia cases in the general population [30 and 30.1].

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

This procedure calls for a routine monitoring of blood-flow to the brain, similar to how blood-pressure is routinely tested [31]. It would allow for a timely clinical/pharmacological intervention to take place, and correct the condition of cerebral hypo-perfusion, where it occurs [32 and 32.1].

If you are in a position to influence the undertaking of such a research project (or, otherwise, can get the word out) I urge you 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 deficiency is fairly common in the elderly [25], in all likelihood, and often even in much younger adults [33 to 38]. It, therefore, likely to cause an increase of the brain temperature and is liable to result in damage to brain-cells [39 to 40.1]. It ought to be in particular true where the condition becomes chronic and lingers on silently for years without being directly detected; way before any symptoms of dementia manifest themselves [41 to 84.1].

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 whether you do, or you don't accept it as a possible cause, would you consider routine monitoring of brain-blood-flow to be of any use? Bearing in mind that blood pressure is not necessarily indicative of cerebral blood flow [85 to 88].

Monitoring brain-blood-flow can be readily accomplished nowadays. Although, being even less invasive, it could be somewhat more cumbersome of that of blood-pressure measurement. However, ultimately it bound to be just as simple as, say, taking 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=

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.)

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

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.)

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

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.)

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

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.)

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

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.)

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

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.)

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

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.)
Back ↑

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

P.S.

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

1.
The dark sides of amyloid in Alzheimer's disease pathogenesis
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
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.)
Back ↑

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

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.)

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

6.
Understanding the cause of sporadic Alzheimer's disease
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

"...the neuropathological lesions of the ... glutaminergic system arising from the neurons of the association cortices ... capable to INITIATE ... neuropathological lesions of this neuronal system, such as the neurofibrillary 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 ↑

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

9.
Tibetan medicine ... treatment of Alzheimer disease
By: Jing-Ming Shi et al.
Int J Clin Exp Med. 2015 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.)
Back ↑

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

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.)
Back ↑

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

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.
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."
(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 HYPOPERFUSION ...
By: Abbie C Johnson et al.
J Cereb Blood Flow Metab. 2020 Apr.
DOI: 10.1177/0271678X19848510

... 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.
Cortical cerebral microinfarcts predict cognitive decline in memory clinic patients
By: Saima Hilal et al.
J Cereb Blood Flow Metab. 2020 Jan.
DOI: 10.1177/0271678X19835565

"Cortical cerebral microinfarcts together with other CEREBROVASCULAR disease markers can be used to design clinical trials in vascular cognitive impairment."
(emph. added j.t.)

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

12.06.
Parietal PERFUSION ALTERATIONS in Parkinson's Disease ...
By: Laura Pelizzari et al.
Front Neurol. 2020 Jun 23;11:562
DOI: 10.3389/fneur.2020.00562

... Parietal cerebral blood flow may be considered as a suitable early biomarker for longitudinal studies investigating cognitive decline in Parkinson's disease ...
(emph. added j.t.)

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

12.07.
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.)

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

12.08.
.... 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.

"....associated with dementia. This association is thought to be mediated by HYPOPERFUSION."
(emph. added j.t.)

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

12.09.
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.)
Back ↑

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

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 ..."

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

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 pathogenesis, which is primarily responsible for Alzheimer's disease ... seems to involve chronic hypoperfusion ... The role of HYPOPERFUSION, as a key factor ... appears to be widely accepted as an initiator of Alzheimer's disease ...
(emph. added j.t.)

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

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.)
Back ↑

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

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
PMID: 26705676
PMCID: PMC4821735
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 PERFUSION 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.
"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.)

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

18.
"... 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.)

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

19.
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.)

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

20.
"CEREBRAL BLOOD FLOW reductions in Alzheimer's disease patients and related mouse models have been recognized for decades ..."
By: Jean C. Cruz, et al.
Nature Neuroscience
volume 22, pages: 413-420 (2019)
(emph. added j.t.)

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

21.
Late-Onset Dementia: Structural Brain Damage and Total CEREBRAL BLOOD FLOW
By: Aart Spilt MD, et al.
RadiologyVolume 236, Issue 3Sep 1 2005

"... BLOOD FLOW in 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 ..."
Back ↑

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

22.
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.)

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

23.
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.)

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

24.
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.)


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

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.
... 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.)

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

27.
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.)
Back ↑

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

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.)
Back ↑

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

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.)
Back ↑

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

30.
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 ...

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

30.1.
"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 ↑

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

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.)
Back ↑

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

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.)
Back ↑

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

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.)

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

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." ...
Back ↑

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

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.)

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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 ...
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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.)

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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.)

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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.)

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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.)

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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.)
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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.)

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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.)

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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.)

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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.)

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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.)
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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.)

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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.)

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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.)

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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.)

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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.)
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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.)

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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.)

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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.)

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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.)

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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.)
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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.)

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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.)

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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.)

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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.)

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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.)
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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.)

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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.)

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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 ..."
(emph. added j.t.)

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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.)

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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.)
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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.)

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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.)

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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.)

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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.)

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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.)
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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.)

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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.)

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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.)

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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.)

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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.)
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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.)

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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.)

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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.)

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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 ..."

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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.)
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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."
(emph. added j.t.)

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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.)

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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.)

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

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