Alzheimer's & dementia : the journal of the Alzheimer's Association · 2026
Intraindividual cognitive variability predicts amyloid beta, tau PET, and dementia conversion in Down syndrome: a potential marker of cognitive resilience.
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Fonseca Luciana Mascarenhas, Lila Eardi, Shojaie Ali, Chhatwal Jasmeer, Forlenza Orestes, Beeri Michal Schnaider, Krinsky-McHale Sharon, Cohen Ann D, Christian Bradley T, Head Elizabeth, Mapstone Mark, Handen Benjamin, Ances Beau M, Grabowski Thomas, Chaytor Naomi S, Zaman Shahid, Alzheimer's Biomarkers Consortium‐ Down Syndrome (ABC‐DS) Investigators
Аннотация
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.
METHODS: Adults from the Alzheimer's Biomarker Consortium-DS (ABC-DS) study (N = 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.
RESULTS: Greater IICV predicted incident MCI/dementia (odds ratio = 4.63 to 5.13, p < 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.
DISCUSSION: IICV is a sensitive marker of dementia risk and cognitive resilience in DS, with potential utility for secondary prevention and trial enrichment.
METHODS: Adults from the Alzheimer's Biomarker Consortium-DS (ABC-DS) study (N = 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.
RESULTS: Greater IICV predicted incident MCI/dementia (odds ratio = 4.63 to 5.13, p < 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.
DISCUSSION: IICV is a sensitive marker of dementia risk and cognitive resilience in DS, with potential utility for secondary prevention and trial enrichment.