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Frailty, neuropathological burden and clinical severity: A cross‐sectional analysis of data from the National Alzheimer’s Coordinating Center
Author(s) -
Ward David D,
Wallace Lindsay MK,
Rockwood Kenneth
Publication year - 2020
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 - 10.1002/alz.038003
Subject(s) - clinical dementia rating , neurofibrillary tangle , neuropathology , dementia , medicine , pittsburgh compound b , alzheimer's disease , autopsy , pathological , cerebral amyloid angiopathy , senile plaques , gerontology , disease , pathology
Background Within the National Alzheimer’s Coordinating Center (NACC) dataset, we quantified the associations of frailty and global neuropathological burden with clinical dementia severity, and explored whether frailty influences the expression of dementia at a given level of neuropathology. Method The sample included 2,621 individuals who had available clinical data and had undergone autopsy within 24 months of their last study visit. A 32‐item frailty index (FI) was calculated retrospectively using the deficit accumulation approach, and a measure of global neuropathological burden (NP) was calculated using a similar index approach from 12 markers of brain disease (e.g. neurofibrillary tangle Braak stage, density of neocortical neuritic plaques, severity of cerebral amyloid angiopathy, presence of microinfarcts). Linear models were used to model the change in the 18‐point Clinical Dementia Rating Scale sum of boxes score (CDR‐SB) per 10% increase in either the FI score or NP score, after adjusting for age, sex, education level, primary language, time from clinical assessment to autopsy, and APOE ε4 allelic status. Result The analytical sample was 80.8 years old ( SD = 9.4 years, range = 60 – 100 years), on average. Each 10% increase in either measure was associated with a significantly higher CDR‐SB (FI: 2.41 points [95% CI = 2.27, 2.56]; NP: 0.87 points [95% CI = 0.73, 1.01]). A significant interaction indicated that the relationship between NP and CDR‐SB became weaker for each 10% increase in FI ( P = .001). The largest increase in CDR‐SB due to a 10% increase in NP was observed among the least frail individuals (FI < 0.3; 1.15 points [95% CI = 0.91, 1.39]), with smaller and similar increases in CDR‐SB observed in both medium (FI ≥ 0.3; 0.77 points [95% CI = 0.47, 1.07]) and high frailty (FI ≥ 0.5, 0.73 points [95% CI = 0.39, 1.07]) groups. Conclusion An increasing degree of frailty and neuropathology are each independently associated with more severe impairment. Among the least frail individuals, neuropathological burden is closely related to clinical function, whereas clinical impairment may occur even at a low level of neuropathology in those who are more frail.