Brief Communication

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

Corresponding Author

Willa D. Brenowitz PhD, MPH

[email protected]

orcid.org/0000-0002-0902-6720

Departments of Psychiatry and Behavioral Sciences, Epidemiology and Biostatistics, University of California, San Francisco, San Francisco, California, USA

Address correspondence to Dr Brenowitz, Department of Psychiatry and Behavioral Sciences University of California, San Francisco, 4150 Clement Street, San Francisco, CA 94158. E-mail: [email protected]

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Myriam Fornage PhD,

Myriam Fornage PhD

The University of Texas, Health Science Center at Houston, Houston, Texas, USA

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Lenore J. Launer PhD,

Lenore J. Launer PhD

Laboratory of Epidemiology and Population Science, National Institute on Aging, Bethesda, Maryland, USA

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Mohamad Habes PhD,

Mohamad Habes PhD

Neuroimage Analytics Laboratory and Biggs Institute Neuroimaging Core, Glenn Biggs Institute for Neurodegenerative Disorders, University of Texas Health Science Center at San Antonio, San Antonio, Texas, USA

Center for Biomedical Image Computing and Analytics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA

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Christos Davatzikos PhD,

Christos Davatzikos PhD

Department of Radiology, University of Pennsylvania, Philadelphia, Pennsylvania, USA

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Kristine Yaffe MD,

Kristine Yaffe MD

Departments of Psychiatry and Behavioral Sciences, Epidemiology and Biostatistics, University of California, San Francisco, San Francisco, California, USA

Department of Neurology, University of California, San Francisco, San Francisco, California, USA

San Francisco VA Medical Center, San Francisco, California, USA

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Willa D. Brenowitz PhD, MPH,

Corresponding Author

Willa D. Brenowitz PhD, MPH

[email protected]

orcid.org/0000-0002-0902-6720

Departments of Psychiatry and Behavioral Sciences, Epidemiology and Biostatistics, University of California, San Francisco, San Francisco, California, USA

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Myriam Fornage PhD,

Myriam Fornage PhD

The University of Texas, Health Science Center at Houston, Houston, Texas, USA

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Lenore J. Launer PhD,

Lenore J. Launer PhD

Laboratory of Epidemiology and Population Science, National Institute on Aging, Bethesda, Maryland, USA

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Mohamad Habes PhD,

Mohamad Habes PhD

Center for Biomedical Image Computing and Analytics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA

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Christos Davatzikos PhD,

Christos Davatzikos PhD

Department of Radiology, University of Pennsylvania, Philadelphia, Pennsylvania, USA

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Kristine Yaffe MD,

Kristine Yaffe MD

Departments of Psychiatry and Behavioral Sciences, Epidemiology and Biostatistics, University of California, San Francisco, San Francisco, California, USA

Department of Neurology, University of California, San Francisco, San Francisco, California, USA

San Francisco VA Medical Center, San Francisco, California, USA

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First published: 13 December 2022

https://doi.org/10.1002/ana.26569

Citations: 3

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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

Potential Conflict of Interest

WDB, MF, MH, and KY report grant funding from NIH. None of the funding sources had involvement in the conduct of this research or preparation of the manuscript. Unrelated to this current study, KY is a Board Member of Alector.

Open Research

Data Availability Statement

CARDIA data is available for approved research projects, see more details at https://www.cardia.dopm.uab.edu/.

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Volume93, Issue3

March 2023

Pages 629-634

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

Abstract

Potential Conflict of Interest

Open Research

Data Availability Statement

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

Abstract

Potential Conflict of Interest

Open Research

Data Availability Statement

References

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