Comparing longitudinal impact of LATE and Alzheimer’s neuropathologic changes in the oldest old

Abstract

AbstractBackgroundLimbic predominant age related TDP‐43 encephalopathy‐neuropathologic change (LATE‐NC) is prevalent in the oldest old and clinically, it mimics Alzheimer’s disease. Our aim was to determine the association between longitudinal change in clinical and neuropsychological measures and the common neurodegenerative diseases in an exclusively oldest‐old cohort to establish features that help distinguish LATE‐NC from Alzheimer disease neuropathologic change (ADNC) during life.Method412 participants from The 90+ Study with longitudinal evaluations and autopsy data were studied. We dichotomized the neuropathologic features and considered the following as the criteria for presence: any degree (mild, moderate or severe) of LATE‐NC, cerebral amyloid angiopathy (CAA), arteriolosclerosis, and hippocampal sclerosis; moderate or severe likelihood of ADNC (according to NIA‐AA criteria); limbic, transitional, or neocortical Lewy bodies (LB); two or more microvascular lesions (MVLs); and severe atherosclerosis. Longitudinal scores of Clinical Dementia Rating Sum of the Boxes (CDR‐SB) and 13 neuropsychological tests grouped into 7 cognitive domains were standardized. We studied the longitudinal relationship between CDR‐SB and each of the 7 cognitive domains with the neuropathologic changes using linear mixed effect models that included all neuropathologic changes adjusting for age at death, sex, and education. P‐values were corrected for multiple comparisons.ResultTable 1 summarizes the characteristics of the participants. LATE‐NC was present in 36% of the cohort and 51% of those who died with dementia. Figure 1 demonstrates the association of pathologic features with CDR‐SB and cognitive outcomes in a model that included all pathologies and was adjusted for multiple comparisons. At time of death, both LATE‐NC and ADNC were associated with worse performance in CDR‐SB, global cognition, memory, language, and orientation. Longitudinally, out of the two diseases, only LATE‐NC was associated with significant decline in CDR‐SB and orientation, and neither were associated with significant longitudinal decline in other cognitive domains including memory.ConclusionOur results confirm the high prevalence and important cognitive consequences of LATE‐NC in the oldest old. Remarkable similarity of cognitive signature of LATE‐NC and ADNC highlight the need for biomarkers capable of distinguishing these two consequential diseases of the oldest old.