The Alzheimer’s disease (AD) story has not changed in years.  Doctors cannot cure it and researchers struggle to understand how it starts and progresses.  Evidence gleaned from numerous clinical trials reveals dementias are complicated and our first notions about how to combat them were probably too simplistic.

Although attempts to mitigate AD achieved only limited success, some recent news has been encouraging.  Despite demographic and health trends anticipated to increase AD levels, dementia rates seem to be on the decline (1).  The decrease is real, but the problem is no one can explain the underlying reason(s) for it.  By and large AD research has been focused more on unraveling molecular mechanisms and finding cures than classic epidemiology.  However, the good news is the decline in dementia rates suggests AD risk factors or the clinical course of cognitive failure may be modified by the environment or behaviors.

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Cardiovascular system malfunction is a well-recognized general risk factor for dementia.  Perhaps better medical management of glucose, blood pressure and cholesterol levels have helped decrease AD by improving overall vascular system function.  Post mortem studies have established AD brain pathology is correlated with the presence of coronary artery disease and hypertension (2) as well as atherosclerosis of the arteries composing the Circle of Willis at the base of the brain (3).

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 A large scale study of persons taking statins to control cholesterol levels revealed those who took the drugs regularly had a decreased likelihood of developing AD (4).  The idea that already FDA-approved and widely used cholesterol modulating drugs might limit the AD threat has been both tantalizing and frustrating researchers for years (5).  However, recent investigations underscore the fact that the natural history of dementia pathology is complex (6).  It is possible that all statins are not equally efficient in preventing AD or that some subjects may be refractory to such treatments.  In addition, many AD patients may suffer from a double dose of vascular failures.  The blood vessels within the brains of AD subjects often exhibit extensive amyloid deposits that probably interfered with essential tissue perfusion and fluid flows (7).  The cognitive collapse of AD may be due to the combined impacts of damage inflicted directly on the brain tissue and its essential blood vessels. 

amyloid-vessel

Amyloid deposits are a defining hallmark of AD and have been the prime target for therapeutic interventions.  While an incredible amount of knowledge has been amassed regarding how amyloid molecules are produced, no one knows why they are produced.  Do these evolutionarily-conserved peptides perform a useful function(s) (8) or are they strictly pathological?  Should we work to eradicate them or is that strategy ultimately more dangerous than helpful?  It is interesting to ponder that these fundamental questions are still debated by AD researchers.

A simple cure for AD is not forthcoming any time soon.  For the moment the hope to control AD hinges on understanding the many factors – direct and indirect – that collectively dictate our risk of developing dementia.  The contributions of environmental contaminants are uncertain, but as information revealing the links of factors like air pollution to dementia risk (9) are validated, it becomes possible to control or avoid them.  A substantial body of evidence suggests several behavioral factors such as healthy dietary regimens, regular exercise and high educational attainment improve one’s prospects for evading AD.  A well-balanced diet and exercise are important to maintain good cardiovascular function and perhaps those actions also preserve brain function indirectly.  Education may influence a host of factors bearing on the prospects for successful aging including occupation and stress.  Our understanding of AD is impressive, but the gaps in it are large.                     

The evidence in hand strongly suggests AD risk can be reduced through proactive actions such as taking steps to maintain good cardiovascular function.  The take home message is clear; while we hope for an AD cure, do everything you can to keep your heart in the game.

(1) G. Kolata. 2016.  U. S. Dementia Rates are Dropping Even as Population Ages.  The New York Times, 21 November 2016.   http://nyti.ms/2eYS0zC

(2) D. L. Sparks.  Coronary Artery Disease, Hypertension, ApoE and Cholesterol: A Link to Alzheimer’s Disease?  Annals of the New York Academy of Sciences 826:128-146. https://www.ncbi.nlm.nih.gov/pubmed/9329686

(3) A. E. Roher et al. 2003.  Circle of Willis Atherosclerosis is a Risk Factor for Sporadic Alzheimer’s Disease.  Arteriosclerosis, Thrombosis and Vascular Biology 23:2055-2062.   http://atvb.ahajournals.org/content/23/11/2055.long

(4) G. D. Zakaib. 2016.  Once Again, Statins Found to Reduce Alzheimer’s Risk.  Alzforum, 14 December 2016.   http://www.alzforum.org/news/research-news/once-again-statins-found-reduce-alzheimers-risk

(5) M. N. Sabbagh and D. L. Sparks. 2009. On Cholesterol Levels and Statins in Cognitive Declines and Alzheimer’s Disease; Progress and Setbacks.  Alzheimer Disease and Associated Disorders 23(4):303-305.    https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2784643/pdf/nihms127305.pdf

(6) S. E. Monsell et al. 2015.      APOE4 Carriers and Non-carriers with the Clinical Diagnosis of Alzheimer’s Dementia and Minimal Amyloid Plaques.  Journal of the American Medical Association Neurology 72(10):1124-1131.   https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4833059/

(7) A. E. Roher et al. 2003.  Cortical and Leptomeningeal Cerebrovascular Amyloid and White Matter Pathology in Alzheimer’s Disease.  Molecular Medicine 9:112-122.  https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1430731/

(8) T. A. Kokjohn et al. 2012.  Is Alzheimer’s Disease Amyloidosis the Result of a Repair Mechanism Gone Astray?  Alzheimer’s & Dementia 8:574-583. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3984046/

(9) H. Devlin. Living Near Heavy Traffic Increases Dementia Risk, Say Scientists.    The Guardian, 5 January 2017 https://www.theguardian.com/society/2017/jan/04/living-near-heavy-traffic-increases-dementia-risk-say-scientists

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