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

---Alzheimer's Association


Dr. Alois Alzheimer declared in 1906 that 'plaques' and 'tangles' are the hallmarks that cause the disease bearing his name [41 to 47]. 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 [40].

By 2050 Dementia is expected to occur every 33 seconds in the U.S. alone (nearly double the rate of the presently diagnosed disease).

This inevitably prompts to question:

Should the Cause of Dementia be Revisited?

The following information appears to have significant implication to fight for conquering the dementia plague. I thought it will be of interest since it promises a breakthrough.

Ample supporting data already available from a good number of independent studies suggesting that cerebral hypo-perfusion is the root cause of dementia [3 to 39]. 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 [1,2]. Certain percentage of those may show brain-blood-flow which, usually, expected in dementia cases regardless of subject age or health condition [12] [20].
This percentage may, eventually, agree with the percentage of dementia cases in the general population.

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. It would allow a timely clinical/pharmacological intervention to take place and correct the condition of cerebral hypo-perfusion where it occurs.

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, in all likelihood, and often even in much younger adults [2]. It, therefore, likely to cause an increase of the brain temperature and is liable to result in damage to brain-cells [38]. 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 [3] [7] [13] [16] [18] [19] [21] [22] [25].

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 [32].

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
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 1967with1 Read
DOI: 10.3181/00379727-124-31788 Source: PubMed

"... Intracerebral temperature gradients are basically dependent upon the rate of REMOVAL of heat from the brain by the arterial 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.
Pathophysiology of HYPOPERFUSION of the Precuneus
in Early Alzheimer's Disease

By: J Scott Miners et al.
Brain Pathol. 2016 Jul;26(4):533-41
DOI: 10.1111/bpa.12331

"The EARLIEST decline in cerebral perfusion in Alzheimer's disease ..."
(emph. added j.t.)

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

2.
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 it may be OBSERVED in some subjects as EARLY as in the third or fourth decades of life ..."
(emph. added j.t.)
Back ↑

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

3.
... 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.)
Back ↑

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

4.
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.)

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

5.
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.)

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

6.
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.)

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

7.
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 [and] 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.)

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

8.
"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

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

9.
"... brain blood flow deficits are one of the earliest detectable symptoms of dementia"
By: Jean C.Cruz Hernandez et al.
published in Nature Neuroscience

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

10.
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."

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

11.
"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)

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

12.
Late-Onset Dementia: Structural Brain Damage and Total CerebralBlood 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 ↑

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

13.
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.)

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

14.
... 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.)

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

15.
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.)

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

16.
CHRONIC 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

"... 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.)

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

17.
Post-mortem assessment of hypoperfusion of cerebral cortex in Alzheimer's disease and vascular dementia
By: Taya Thomas et al.
Brain 2015 Apr;138(Pt 4):1059-69
DOI: 10.1093/brain/awv025

"Perfusion is reduced in the cerebral neocortex in Alzheimer's disease ..."

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

18.
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.)

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

19.
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.)

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

20.
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 ..."
Back ↑

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

21.
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 that influences the progression from mild cognitive impairment to dementia ... We suggest that in RESPONSE TO HYPOPERFUSION, INCREASED BETA AMYLOID production/deposition ..."
(emph. added j.t.)

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

22.
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.)

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

23.
... 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 ..."

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

24.
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."

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

25.
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 ↑

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

26.
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.)

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

27.
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.)

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

28.
Leaky memories: Impact of APOE4 on blood's brain barrier and dementia
Wenlu Li et al.
By: 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."

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

29.
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.)

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

30.
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.)

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

31.
Cortical cerebral microinfarcts PREDICT COGNITIVE DECLINE in memory clinic patients
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.)

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

32.
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.)
Back ↑

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

33.
.... 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.)

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

34.
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.)

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

35.
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.)

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

36.
... 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.)

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

37.
... 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.)

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

38.
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.)
Back ↑

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

39.
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 ↑

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

40.
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.)
Back ↑

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

41.
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 (AD) ... RAISES THE QUESTION as to whether accumulation of amyloid beta peptides IS INDEED the culprit for neurodegeneration in AD."
(emph. added j.t.)

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

42.
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.)

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

43.
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.)

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

44.
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.)

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

45.
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.)

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

46.
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.)

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

47.
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."
Back ↑