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P1‐436: UTILITY OF A GENETIC RISK ASSESSMENT FOR IMPROVED CLINICO‐PATHOLOGIC CORRELATIONS
Author(s) -
Spencer Barbara E.,
Digma Leonardino A.,
Murphy Elizabeth A.,
Jennings Robin G.,
Fan Chun Chieh,
Desikan Rahul S.,
Dale Anders M.,
Brewer James B.
Publication year - 2019
Publication title -
alzheimer's and dementia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 6.713
H-Index - 118
eISSN - 1552-5279
pISSN - 1552-5260
DOI - 10.1016/j.jalz.2019.06.1041
Subject(s) - dementia with lewy bodies , senile plaques , medicine , neuropathology , autopsy , pathological , pathology , disease , atrophy , apolipoprotein e , alzheimer's disease , differential diagnosis , dementia
neuropathological examination to identify pathologic diagnosis of AD (NIA-Reagan criteria), presence of neocortical Lewy bodies (LB), TDP-43 pathology extending beyond the amygdala, hippocampal sclerosis (HS), and vascular pathologies (multiple macroinfarcts or cortical microinfarcts, moderate to severe atherosclerosis, arteriolosclerosis, or cerebral amyloid angiopathy). Persons were grouped based on age-at-death; <80 (n1⁄495), 80-84 (n1⁄4176), 8589 (n1⁄4328), 90-94 (n1⁄4377), 95-99 (n1⁄4200), and 100+ (n1⁄461). Analyses included tests for trend and log-binomial regression models. Results: Of 1,237 participants, 515 had dementia, 293 hadMCI, and 429 had normal cognition proximate to death (mean 11 months before autopsy). Proportion of mixed pathologies was lowest (28%) in the youngest group and highest (69%) in the oldest (ptrend <0.001), while proportion with isolated AD pathology did not vary (<10%, p-trend1⁄40.72). In those with normal cognition, proportions with mixed pathologies ranged from 19% (youngest) to 54% (oldest) (p-trend<0.001); there was no significant difference by age group in the MCI group (p-trend1⁄40.06) or dementia group (73%-79%, p-trend1⁄40.49). Observing specific combinations of pathologies in the total group, AD+Lewy bodies did not vary across age groups (3%-8%, p-trend1⁄40.56); however, while proportions with AD+TDP-43/HS (4%-43%, p-trend<0.001) and AD+vascular (24%-66%, p-trend<0.001) did. In interaction models adjusted for sex, education, and other pathologies, the association between each mixed pathology combination and dementia was attenuated at higher ages. Conclusions: Across all cognitive statuses, the proportion of mixed pathologies is higher in older age, while the proportion with single pathologies remained constant. Over 75% of persons with dementia displayed mixed pathologies, independent of age. TDP-43/HS and vascular pathologies account for more mixed pathologies, proportionately, at older ages. At older ages, the association of mixed pathologies with dementia is attenuated.