ArticleAlzheimer's & dementia : the journal of the Alzheimer's Association2023
Cognitive trajectories diverge by genetic risk in a preclinical longitudinal cohort.
Article in Alzheimer's & dementia : the journal of the Alzheimer's Association, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.
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Who cites it
9 citing papers in PubMed.
- Associations between polygenic risk for obesity, body mass index and cognitive performance: Age as moderating factor.Brain, behavior, & immunity - health · 2026Article
- A multiancestry polygenic risk score for Alzheimer's disease is associated with cognitive decline and neuropathological hallmarks in diverse populations.Nature genetics · 2026Article
- PreoperativeFrontiers in bioinformatics · 2026Review
- Linking silent pause locations in speech to amyloid and tau deposition in cognitively unimpaired individuals.Journal of Alzheimer's disease : JAD · 2025Article
- A multi-ancestry polygenic risk score for Alzheimer disease is associated with cognitive decline, hippocampal atrophy and neuropathological hallmarks in diverse populations.medRxiv : the preprint server for health sciences · 2025Article
- Dynamics of cognitive variability with age and its genetic underpinning in NIHR BioResource Genes and Cognition cohort participants.Nature medicine · 2024Article
- Pet Ownership, Living Alone, and Cognitive Decline Among Adults 50 Years and Older.JAMA network open · 2023Article
- Effect of Pathway-Specific Polygenic Risk Scores for Alzheimer's Disease (AD) on Rate of Change in Cognitive Function and AD-Related Biomarkers Among Asymptomatic Individuals.Journal of Alzheimer's disease : JAD · 2023Article
- Harnessing cognitive trajectory clusterings to examine subclinical decline risk factors.Brain communications · 2023Article
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6 authors.
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Abstract
introductionWe sought to characterize the timing of changes in cognitive trajectories related to genetic risk using the apolipoprotein E (APOE) score, a continuous measure of Alzheimer's disease (AD) risk. We also aimed to determine whether that timing was different when genetic risk was measured using an AD polygenic risk score (PRS) that contains APOE.
methodsWe analyzed trajectories (N ≈1135) for four neuropsychological composite scores using mixed effects regression for longitudinal change across APOE scores and PRS of participants in the Wisconsin Registry for Alzheimer's Prevention, a longitudinal study of adults aged 40 to 70 at baseline, with a median participant follow-up time of 7.8 years.
resultsWe found a significant non-linear age-by-APOE score interaction in predicting cognitive decline. Cognitive trajectories diverged by APOE score at approximately 65 years of age. A 0.5 standard deviation difference in cognition between extreme percentiles of the PRS was predicted to occur 1 to 2 years before that of the APOE score. DISCUSSION: Cognitive decline differs across time and APOE score. Estimates did not substantially shift with the AD PRS. HIGHLIGHTS: The apolipoprotein E (APOE) score, a continuous measure, accounts for non-linear genetic risk of Alzheimer's disease. Non-linear age interacts with the APOE score to affect cognition. Cognitive decline starts to differ by APOE score levels at approximately age 65. Cognitive decline timing by polygenic risk (including APOE) is similar to APOE alone.
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