Why and how some people develop Alzheimer’s disease (AD) is not clear. Although advancing age is a recognized risk factor, not all elderly persons succumb to AD. The environmental and behavioral factors that seem to help guard against dementia are also understood only in vague terms. Scientists are now making systematic efforts to assess the specific contributions of a feature loosely known as ‘cognitive reserve’ to successful brain aging (1).
Cognitive reserve is invoked to explain why certain people known to have harbored pathological changes linked to AD somehow resisted falling prey to dementia. Ideally, scientists suspect it might be beneficial to figure out how to boost cognitive reserve, but first they will have to clarify what it is. Educational attainment and continued intellectual stimulation are associated with cognitive reserve in that persons with greater levels of them tend to show slower mental declines, but that is about as precise as anyone can get at the moment.
Physical exercise is also correlated with better brain health. This could reflect the fact that exercise maintains vascular function which, in turn, would allow continued good brain perfusion. Perhaps cognitive reserve represents a complex balance reflecting how neurons were trained and interconnected early in life, the functional demands placed on them after maturity combined with the capacity of the cardiovascular system to supply the brain with oxygen and nutrients.
Dietary habits also play a key role in AD development with consumption of high levels of fat and sugar associated with a clearly greater threat of dementia. Recent work has revealed that the brain is linked to complex feedback loops involving the digestive, immune and hormone systems (2). Adding to the complexity, a diverse community of metabolically active microbes in the gut – the microbiome – makes substantial inputs into normal, and abnormal, brain function. The mind-gut link is sensitive to what you eat and what the resident microbes in your gut make of it.
The cognitive reserve hypothesis is an attempt to explain the frustrating heterogeneity of AD. How can equivalent levels of amyloid deposits and neurofibrillary tangles produce dementia in one patient while another remains functional? This variability turns up even in persons carrying a genetically dominant point mutation which produces an early-onset form of AD (3). Studies of a large group of persons carrying a mutation known as Paisa have revealed that the median age of dementia onset is around 49 years. However, the range of onset varies between 30-80 years of age (3). This variability among persons with the identical Paisa mutation has been long noted and suggests environmental or behavioral factors are somehow influencing the disease course (4). Some members of this extended Paisa mutation kindred are now participating in clinical trials designed to prevent or delay AD onset (5). In addition, extensive medical records are available for hundreds of Paisa-affected persons (3). This may present an ideal opportunity to examine hypotheses as to whether the gut microbiome, dietary practices or lifestyles impact the onset of this specific form of AD or influence the attempted clinical trial interventions against it.
Cognitive reserve has been recognized as one of several factors that modify the risk for AD development. No quick cure for AD is at hand, so exploring this factor could make significant contributions to the understanding as to how AD begins or might be evaded. It will be interesting to see how big a role, if any, the gut microbiome plays in maintaining healthy brain function as we age. This potentially important factor has received little attention from AD researchers.
(1) AlzForum, Cognitive Aging Summit III. NIH Summit Examines What Makes a Healthy Aging Brain, 25 April 2017. http://www.alzforum.org/news/conference-coverage/nih-summit-examines-what-makes-healthy-aging-brain
(2) D. Gordon. 2017. Gut Feeling. U Magazine, Spring 2017. https://www.uclahealth.org/gastro/workfiles/newsletters/GutFeelingUMagSpr2017.pdf
(3) J. I. Vélez et al. 2016. A Mutation in DAOA Modifies the Age of Onset in PSEN1 E280A Alzheimer’s Disease. Neural Plasticity 2016:9760314. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4753688/
(4) F. Lopera et al. 1997. Clinical Features of Early-Onset Alzheimer Disease in a Large Kindred with an E280A presenilin-1 mutation. The Journal of the American Medical Association 277(10):793-799. http://jamanetwork.com/journals/jama/fullarticle/414555
(5) Alzheimer’s Prevention Initiative. http://banneralz.org/research-clinical-trials/types-of-research-studies/alzheimer%E2%80%99s-prevention-initiative.aspx