Limbic-predominant age-related TDP-43 encephalopathy in Black and White decedents

Objective The association of limbic-predominant age-related transactive response DNA-binding protein 43 encephalopathy neuropathologic change (LATE-NC) with cognition and dementia was assessed in community-dwelling Black elders, and racial differences in these associations were tested.

Methods Black (n = 76) and White (n = 152) decedents from 4 longitudinal clinical pathologic studies of aging were matched 2 to 1 by age at death, sex, years of education, dementia status, and follow-up time. LATE-NC detected by immunohistochemistry was dichotomized into none/mild and moderate/severe groups. Distribution and clinical and pathologic characteristics of LATE-NC and its association with cognitive profiles and odds of dementia were determined in Black decedents, and racial differences in these associations were assessed.

Results The overall frequency of LATE-NC in Black and White decedents was similar (40.8% vs 45.4%). Black decedents with moderate/severe LATE-NC were older, had significantly lower global cognition scores, particularly in memory domains, and had higher frequency of Alzheimer disease, hippocampal sclerosis, and cerebral amyloid angiopathy than the LATE-NC none/mild group. LATE-NC in Black decents was independently associated with impaired global cognition, episodic and semantic memory, and visuospatial abilities. There were no racial differences in clinical features or pathologic distribution of LATE-NC except for a significant increase in the mean cytoplasmic inclusions in the entorhinal and mid temporal cortices in White compared to Black decedents. In addition, no racial differences in the cognitive profiles or the odds of dementia were observed in Black vs White decedents.

Conclusions Consistent with findings in White decedents, LATE-NC in Black decedents is associated with impaired cognition, including memory domains.