Diseases Over Decades: Alzheimers

I have emphasized time and time again that many of the disease we are fighting in order to live longer and healthier lives initiate their disease process decades before we as humans feel any of the disease symptoms. This is true for cardiovascular disease, insulin resistance and diabetes, dementia, and cancer amongst others.

In this post I would like to share an article published in the journal The Proceeding of the National Academy of Sciences (PNAS) in May of 2020 that reiterates this idea specifically with Alzheimer's disease.

The study by Gary W. Small et al. (2000) investigated cerebral metabolic and cognitive decline in individuals at genetic risk for Alzheimer’s Disease (AD), focusing on 65 participants aged 50 to 84, including 54 nondemented individuals (27 APOE-4 carriers and 27 non-carriers) and 11 subjects with probable AD. Using PET scans and cognitive testing at baseline and after a 2-year follow-up in a subset of 20 nondemented subjects, the study found that APOE-4 carriers showed significantly lower glucose metabolism in the inferior parietal, lateral temporal, and posterior cingulate regions — areas vulnerable to early AD pathology — compared to non-carriers. Over 2 years, APOE-4 carriers experienced a 4-5% decline in these regions, while non-carriers exhibited only age-related changes in the frontal cortex. Despite stable cognitive test scores, lower baseline metabolism predicted cognitive decline exclusively in APOE-4 carriers, suggesting that combining genetic risk with PET imaging could enable early detection of preclinical AD, improve clinical trial efficiency, and support early intervention before cognitive symptoms arise.

Translating that to english, the study took individuals either with Alzheimer's Disease, at high risk for Alzheimer's Disease, or at low risk for Alzheimer's Disease and compared their brain imaging over a 2 year interval. They found that individuals with high risk of Alzheimers Disease began manifesting detectable metabolic disturbances that proceeded AND predicted cognitive decline. Again, the disease process takes place years before the symptomatology.

Some notable quotes from the study:

"Moreover, in subjects at genetic risk for AD, lower baseline metabolism predicted future cognitive decline, and the greatest metabolic decline after 2 years was observed in the parietal and temporal cortices, areas that show extensive early deposition of neuropathological lesions in patients with AD"

"We found that glucose metabolic rates correlated with memory performance decline 2 years later in APOE-4 carriers."

"The observation that metabolic patterns predict cognitive decline in presymptomatic persons indicates that the pathophysiologic process begins well before even mild or questionable dementia is recognized clinically."

I am firmly in the camp of those that feel dementia, even in those dealt a 'poor genetic hand', is not on an inevitable timeline, and having such genes does not seal someone to a fate of early dementia. Yes, if one follows the typical American lifestyle complete with the Standard American Diet, poor exercise, abysmal sleep, and high stress, these genetic factors will accelerate the dementing process. BUT if you 'do all the right things' early and consistently, you can markedly intervene and delay this process.

I feel like Peter Attia said it best in an excerpt from his book Outlive as he is revealing to a patient the finding that she carried two copies of the ApoE 4 gene, greatly increasing her risk of developing Alzheimer's disease:

"I said something like, 'Stephanie, there is something we found in your blood test that may be of concern to me - not because anything is wrong now, but because of the risk it poses in twenty to thirty years or so. You have a combination of genes that increases your risk of developing Alzheimer's disease. But it's also important that you understand that what we're about to discuss is only a marker for risk, not a fiat accompli, and I am convinced that we can mitigate this risk going forward.'"

-Peter Attia, Outlive Page 178

The take home from this study is to reiterate that disease processes starts decades before the disease takes hold, so we too must start decades before the disease takes hold to live our fullest and healthiest lives.

Cite:

G.W. Small, L.M. Ercoli, D.H.S. Silverman, S. Huang, S. Komo, S.Y. Bookheimer, H. Lavretsky, K. Miller, P. Siddarth, N.L. Rasgon, J.C. Mazziotta, S. Saxena, H.M. Wu, M.S. Mega, J.L. Cummings, A.M. Saunders, M.A. Pericak-Vance, A.D. Roses, J.R. Barrio, & M.E. Phelps, Cerebral metabolic and cognitive decline in persons at genetic risk for Alzheimer's disease, Proc. Natl. Acad. Sci. U.S.A. 97 (11) 6037-6042, https://doi.org/10.1073/pnas.090106797 (2000).

Attia, Peter. Outlive: The Science and Art of Longevity. United Kingdom, Harmony/Rodale/Convergent, 2023.

small-et-al-2000-cerebral-metabolic-and-cognitive-decline-in-persons-at-genetic-risk-for-a.

Download • 263KB