Intraindividual cognitive variability predicts amyloid beta, tau PET, and dementia conversion in Down syndrome: a potential marker of cognitive resilience
Source: PubMed Central Open Access, NCBI / U.S. National Library of Medicine
Abstract INTRODUCTION Adults with Down syndrome (DS) are at risk for Alzheimer's disease (AD), yet identifying the preclinical phase remains challenging. Intraindividual cognitive variability (IICV) may be a sensitive marker of early AD‐related changes but remains understudied in DS. alz71537-sec-0010 METHODS Adults from the Alzheimer's Biomarker Consortium–DS (ABC‐DS) study (= 460, mean age 43.3 years; 45.7% female) were included. Generalized linear models examined whether baseline IICV predicted incident mild cognitive impairment (MCI)/dementia, cognitive decline, and amyloid and tau positron emission tomography outcomes, adjusting for demographics, intellectual disability, apolipoprotein E ε4, site, assessment interval, and mean cognitive performance, with Bonferroni correction. alz71537-sec-0020 RESULTS Greater IICV predicted incident MCI/dementia (odds ratio = 4.63 to 5.13,< 0.05), greater amyloid burden, early tau accumulation, and higher tau across Braak stages, independent of mean cognition. Exploratory analyses suggested sex‐specific interactions with tau outcomes. alz71537-sec-0030 DISCUSSION IICV is a sensitive marker of dementia risk and cognitive resilience in DS, with potential utility for secondary prevention and trial enrichment. alz71537-sec-0040 Highlights IICV predicts dementia risk in adults with DS. Higher IICV is associated with amyloid burden and tau PET pathology. Cognitive variability detects clinical vulnerability before overt cognitive decline. Find
Abstract
Abstract INTRODUCTION Adults with Down syndrome (DS) are at risk for Alzheimer's disease (AD), yet identifying the preclinical phase remains challenging. Intraindividual cognitive variability (IICV) may be a sensitive marker of early AD‐related changes but remains understudied in DS. alz71537-sec-0010 METHODS Adults from the Alzheimer's Biomarker Consortium–DS (ABC‐DS) study (= 460, mean age 43.3 years; 45.7% female) were included. Generalized linear models examined whether baseline IICV predicted incident mild cognitive impairment (MCI)/dementia, cognitive decline, and amyloid and tau positron emission tomography outcomes, adjusting for demographics, intellectual disability, apolipoprotein E ε4, site, assessment interval, and mean cognitive performance, with Bonferroni correction. alz71537-sec-0020 RESULTS Greater IICV predicted incident MCI/dementia (odds ratio = 4.63 to 5.13,< 0.05), greater amyloid burden, early tau accumulation, and higher tau across Braak stages, independent of mean cognition. Exploratory analyses suggested sex‐specific interactions with tau outcomes. alz71537-sec-0030 DISCUSSION IICV is a sensitive marker of dementia risk and cognitive resilience in DS, with potential utility for secondary prevention and trial enrichment. alz71537-sec-0040 Highlights IICV predicts dementia risk in adults with DS. Higher IICV is associated with amyloid burden and tau PET pathology. Cognitive variability detects clinical vulnerability before overt cognitive decline. Findings link cognitive heterogeneity to AD neuropathology in DS. Cognitive variability may aid risk stratification and trial enrichment in DS. bullet alz71537-list-0001 highlights