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

doi:10.1002/ana.26569

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

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3 Citas (Scopus)

Resumen

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.

Idioma original	English (US)
Páginas (desde-hasta)	629-634
Número de páginas	6
Publicación	Annals of neurology
Volumen	93
N.º	3
DOI	https://doi.org/10.1002/ana.26569
Estado	Published - mar 2023

ASJC Scopus subject areas

Neurology
Clinical Neurology

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abstract = "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.",

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AU - Brenowitz, Willa D.

AU - Fornage, Myriam

AU - Launer, Lenore J.

AU - Habes, Mohamad

AU - Davatzikos, Christos

AU - Yaffe, Kristine

PY - 2023/3

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N2 - 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.

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

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