- Dugger, Brittany;
- Jin, Lee-Way;
- Vargo, Veronica;
- DeCarli, Charles;
- Johal, Sharanpreet;
- Gilsanz, Paola;
- Mungas, Dan;
- Kawas, Claudia;
- Glymour, Maria;
- Corrada, Maria;
- Whitmer, Rachel
Neuropathology studies of the oldest-old have significantly advanced our understanding
of the multiple etiologies late in very late life; however, this has
been limited to studies of non-Hispanic white (NHW) decedents. The LifeAfter90
study is an ongoing cohort study of integrated healthcare delivery
system members in Northern California, aged 90+ with targeted recruitment
of persons across different racial/ethnic backgrounds with no prior diagnosis
of dementia in their medical record. Brain donation is available to all interested
consenting participants. As of January 2022, 216 participants (26% of
sample) were enrolled in autopsy (autopsy enrollees: 20% Asian, 15% African
American, 17% Latino, 9% Multiracial/Other, and 39% NHW) with 25
deceased and neuropathological evaluations completed. Average age of
death was 95 years (range 91-106), 13 (62.5%) were female, 14 NHW, 6 Latino,
3 Multiracial, 1 Asian, and 1 African American. At final clinical exam,
14 participants were cognitively normal (56%), 8 had questionable/mild cognitive
impairment (32%), and 3 were dementia (12%). With respect to Alzheimer's
disease (AD) neuropathologic diagnosis, no cases had high AD
likelihood, 8 met criteria for intermediate (32%), 11 low (44%), and 6 did not
have AD (24%). All participants had some level of neurofibrillary tangles
(NFTs); median Braak NFT stage was II (range I-V). Six participants lacked
plaques, and highest Thal phase was 4. Eleven participants (44%) had Lewy
bodies. TDP-43 inclusions were detected in 5 participants (20%). The most
common assessed pathologies were ARTAG in 19 participants (76%) and
some degree of arteriolosclerosis in 24 participants (96%) although only 4
were considered to have severe arteriolosclerosis. This diverse cohort of
oldest-old individuals indicate numerous brain pathologies are present with
advanced age, albeit most participants having mild severity and distributions
of pathologies providing further evidence of the complex and multifactorial
nature of clinic-pathological correlations.