Neuropathologic features of cognitively defined Alzheimer's disease subgroups in the Adult Changes in Thought study
Abstract
Abstract
Background
Individuals with Alzheimer's disease (AD) dementia can be subgrouped based on cognitive performance at diagnosis. We compared neuropathology across cognitively defined AD subgroups in the Adult Changes in Thought study.
Methods
Scores for memory, executive functioning, language, and visuospatial abilities were derived from the Cognitive Abilities Screening Instrument and a neurocognitive battery. Subgroups were defined by relative performance within domains. Standardized neuropathologic evaluation was performed post mortem. Associations were estimated using ordinal logistic regression, with odds ratios (OR) and 95% confidence intervals (CIs) comparing neuropathology between the AD subgroups and relative to individuals without dementia.
Results
Of 885 participants with post mortem neuropathology, 370 had AD dementia: 54% AD–no domain, 15% AD–memory, 15% AD–visuospatial, 8% AD–language, and 7% AD–executive. Among AD subgroups, associations were detected for limbic‐predominant age‐related transactive response DNA binding protein 43 kDa encephalopathy neuropathologic change (LATE‐NC; P = 0.019) and hippocampal sclerosis (HS; P = 0.006), with highest levels in AD–language (LATE‐NC OR 2.37, 95% CI 1.03–5.46 and HS OR 2.19, 95% CI 0.88–5.50) and AD–memory (LATE‐NC OR 1.88, 95% CI 1.02–3.46 and HS OR 3.11, 95% CI 1.56–6.20) relative to AD–no domain, and lowest levels in AD–visuospatial. AD–visuospatial tended to have lowest estimated Alzheimer's disease neuropathologic change (ADNC) burden across AD subgroups. Relative to participants without dementia, all AD subgroups expectedly had higher ADNC burden, and several AD subgroups had higher odds of Lewy body pathology (P = 0.017) and gross infarcts (P = 0.004), with broadly similar estimates across multiple AD subgroups.
Discussion
Neuropathologic patterns of ADNC and co‐pathologies across AD dementia subgroups suggest cognitive phenotyping may inform clinicopathologic studies of AD dementia.