Alzheimer's Disease Genetic Risk, Cognition, and Brain Aging in Midlife

Willa D. Brenowitz, Myriam Fornage, Lenore J. Launer, Mohamad Habes, Christos Davatzikos, Kristine Yaffe

Research output: Contribution to journalArticlepeer-review

2 Scopus citations


We examined associations of an Alzheimer's disease (AD) Genetic Risk Score (AD-GRS) and midlife cognitive and neuroimaging outcomes in 1,252 middle-aged participants (311 with brain MRI). A higher AD-GRS based on 25 previously identified loci (excluding apolipoprotein E [APOE]) was associated with worse Montreal Cognitive Assessment (−0.14 standard deviation [SD] [95% confidence interval {CI}: -0.26, −0.02]), older machine learning predicted brain age (2.35 years[95%CI: 0.01, 4.69]), and white matter hyperintensity volume (0.35 SD [95% CI: 0.00, 0.71]), but not with a composite cognitive outcome, total brain, or hippocampal volume. APOE ε4 allele was not associated with any outcomes. AD risk genes beyond APOE may contribute to subclinical differences in cognition and brain health in midlife. ANN NEUROL 2023;93:629–634.

Original languageEnglish (US)
Pages (from-to)629-634
Number of pages6
JournalAnnals of neurology
Issue number3
StatePublished - Mar 2023

ASJC Scopus subject areas

  • Clinical Neurology
  • Neurology


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