Don’t you just love a nice longitudinal cohort study? Wonderful to have an in-depth description of human aging in a specific geometry of spacetime.
Locally, Dr. Eric Larson had led the Adult Changes in Thought Study for about 30 years, following patients at an HMO. It can do data mining on the medical record, and lends itself to symptoms, diagnoses and prescription drug correlations to cognitive change.
In Chicago, Dr. David Bennett has been studying nuns and other clergy in the Religious Order Study about 30 years. One could make speculations about diet and cognitive activity in that kind of cohort, and it may represent a different kind of aging.
What amazes me the most though, are studies of the “oldest old” and the 90+ series, UC-Irvine, started decades ago by Drs. Claudia Kawas and Maria Corrado after an even earlier study. They enrolled subjects from an “active retirement community” south of LA. Their latest papers [2023] compare brains of 90-year-olds to brains of 100-year-olds! Yes, mainly Caucasian, half with college, some might say privileged, but what can we learn?
From that same UC-Irvine website:…….some of the major findings are:
- People who drank moderate amounts of alcohol or coffee lived longer than those who abstained.
- People who were overweight in their 70s lived longer than normal or underweight people did.
- Over 40% of people aged 90 and older suffer from dementia while almost 80% are disabled. Both are more common in women than men.
- About half of people with dementia over age 90 do not have sufficient neuropathology in their brain to explain their cognitive loss.
- People aged 90 and older with an APOE2 gene are less likely to have clinical Alzheimer’s dementia, but are much more likely to have Alzheimer’s neuropathology in their brains.
Putting an optimistic spin on their study Oct 2023, dementia is not inevitable over age 90, in fact fewer than half of the subjects had dementia. As for cause and effect, there is a lot of arteriosclerosis and other pathologies in the oldest old brains, but less than a third had Alzheimer specific pathology. Evidence of past strokes and other abnormalities did add on to Alzheimer pathology, and made the odds of having any dementia worse.
A companion 2023 study looked at “superior” cognitive performance in this age group to correlate with pathology. Although 80% of those with good scores had Alzheimer pathology; they seemed “resilient and resistant” (a theme of these authors) to its effects, and the effects of other brain pathologies, on cognitive performance.
Another companion neuropathology study this year looked at an aggregate of brain autopsy studies from Hawaii (remember my post about Kona coffee?), the Religious Orders Study and the 90+ Study. In 387 brains from persons with severe cognitive impairment, a fifth had only Alzheimer changes, but the rest had a mix of additional pathologies.
Their concluding remark: “we speculate that a future intervention that would fully prevent or ablate all ADNC [Alz Dis Neuropath Changes] might be expected to lower the occurrence of end-of-life severe cognitive impairment from about 37% (approximating today’s level) to 20-30%. A future intervention that would fully block development of all 5 of these common aging-related NC [neuropathologic changes] might reduce the prevalence of end-of-life impairment to about 15%, assuming no substantial change in longevity. These inferences suggest that a future prevention of ADRD may require a better understanding of brain aging and the multiple complex pathogeneses of cognitive decline than now exists.”
So, my take from the pathology perspective: clinical dementia is not all just amyloid-beta and tau; some persons with those findings are OK. If PET scans (which now may be covered by CMS) only pick up amyloid-beta and tau changes, and are used to justify newer FDA approved treatments, will many folks be treated unnecessarily?
Ironically (?), the “ATN” biomarker criteria authors (for diagnoses based on PET scans) now want to demote Neurodegeneration as a criterion, as reported on AlzForum, from the AAIC 2023 Meeting.
MIND Diet: Besides birthday cake and sweets, what else should one eat to be healthy and get older? The MIND Diet, a hybrid of Mediterranean and Dietary Approaches to Systolic Hypertension, has been touted for some time now as a prevention for dementia. A paper this year associates the MIND Diet with cognitive resilience. On the other hand, a randomized trial of about 600 total subjects, starting around age 70, [Aug 2023, NEJM, behind a paywall] showed no statistical differences.
Miscellany: minimal comments, not that one doesn’t have opinions, but not worth writing too much…
“Regular vaccines” associated with prevention? Note that the study, with thousands of subjects, is from a claims data-base. Forbes news article.
Amyloid-beta is a cytokine. A “perspective” article, like a descriptive checklist, but behind a paywall.
For policy geeks 2023, TL;DR myself, but clear graphic:
