Persons over the age of 90 are the fastest growing segment of the population in the US, yet there is a dearth of studies investigating the underlying neuropathology of cognitive impairment and dementias, in ethnically diverse, non-white decedents. The Life after 90 study began enrollment in July 2018 and is an ongoing cohort study of members of Kaiser Permanente Northern California aged 90+ with targeted recruitment of individuals across different racial/ethnic groups with no prior diagnosis of dementia in their medical record. Participants are examined every 6 months. Brain donation was available to all interested consenting participants. Neuropathology was assessed using the National Alzheimer's Coordinating Center Neuropathology form v. 10. As of January 2021, 173 (26%) participants enrolled in autopsy (18% Asian, 12% African American, 12% Latino, and 10% as multiracial) with 8 deceased and neuropathological evaluations completed. Average age of death was 96 years (range 91 to 105), 5 (62.5%) were female, 3 Latino, 3 Caucasian, and 2 multiracial. At the final clinical exam, which was on average 4 months before death (range: 2-8), 2 participant had dementia (25%), 3 questionable/mild cognitive impairment (37.5%), and 3 cognitively normal (37.5%). With respect to a neuropathologic diagnosis of Alzheimer's disease (AD), 2 met criteria for intermediate likelihood (25%), 4 low (50%), and 2 were considered not to have AD (25%). Notably, none had high likelihood of AD. All participants had some level of neurofibrillary tangles with Braak stages between II and IV. Two participants lacked plaques (Amyloid-Beta or neuritic types), and the highest Thal phase was 4. Four participants (50%) had Lewy bodies (LBs), 1 in olfactory bulb/tract only, 2 Transitional, and 1 with Diffuse. Hippocampal sclerosis was not seen in any whereas TDP-43 inclusions were detected in 2 participants (25%). Diffuse LB, TDP-43 inclusions, and intermediate AD co-occurred in one (50%) of the dementia participants while all lacking in the other. Preliminary results of the first 8 deaths in this multiethnic cohort of oldest-old individuals indicate that numerous brain pathologies are present with advanced age. Further work with this study will examine the clinical impact of this pathological heterogeneity.

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.