TY - JOUR AU1 - Robinson, John AU2 - Corrada, Maria AU3 - Kovacs, Gabor AU4 - Dominique, Myrna AU5 - Caswell, Carrie AU6 - Xie, Sharon AU7 - Lee, Virginia AU8 - Kawas, Claudia AU9 - Trojanowski, John AB - The diagnosis of Alzheimer’s disease (AD) in the oldest-old is complicated by the increasing prevalence of age-related neurofibrillary tangles, plaques and non-AD pathologies such as cerebrovascular disease (CVD), hippocampal sclerosis (HS), aging-related tau astrogliopathy (ARTAG), as well as TDP-43 and Lewy pathology. The contribution of these non-AD pathologies to dementia and cognitive resilience is unclear. We assessed the level of AD neuropathologic change (ADNPC) and non-AD pathology in 185 participants enrolled in The 90+ Study with available cognitive assessments and brain tissue. Logistic regression models—adjusting for age, sex and education—determined the association between each pathology and dementia or between subgroups. 53% had dementia, primarily AD or mixed AD; 23% had cognitive impairment without dementia (CIND); 23% were not impaired. Both AD and non-AD pathology was prevalent. 100% had tangles, 81% had plaques, and both tangles and plaques associated with dementia. ARTAG distributed across limbic (70%), brainstem (39%) and cortical regions (24%). 49% had possible CVD and 26% had definite CVD, while HS was noted in 15%. Cortical ARTAG, CVD and HS were each associated with dementia, but limbic and brainstem ARTAGs were not. TDP-43 and Lewy pathologies were found in 36 and 17% and both associated with dementia. No pathology distinguished CIND and the not impaired. By NIA-AA criteria and dementia status, the cohort was subdivided into four groups: those with minimal ADNPC included the not dementia (ND) and Not AD dementia groups; and those with significant ADNPC included the Resilient without dementia and AD dementia groups. Compared to the ND group, the Not AD dementia group had more HS, cortical ARTAG, TDP-43, and Lewy pathology. Compared to the AD dementia group, the Resilient group had less CVD, no HS and less cortical ARTAG, TDP-43 and Lewy pathology. Our findings imply that reductions in non-AD pathologies including CVD contribute to cognitive resilience in the oldest-old. TI - Non-Alzheimer’s contributions to dementia and cognitive resilience in The 90+ Study JF - Acta Neuropathologica DO - 10.1007/s00401-018-1872-5 DA - 2018-06-18 UR - https://www.deepdyve.com/lp/springer-journals/non-alzheimer-s-contributions-to-dementia-and-cognitive-resilience-in-3Y6Yg3hRCO SP - 377 EP - 388 VL - 136 IS - 3 DP - DeepDyve ER -