Dataset Information

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

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.

SUBMITTER: Brenowitz WD

PROVIDER: S-EPMC9974745 | biostudies-literature | 2023 Mar

REPOSITORIES: biostudies-literature

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

Brenowitz Willa D WD Fornage Myriam M Launer Lenore J LJ Habes Mohamad M Davatzikos Christos C Yaffe Kristine K

Annals of neurology 20221225 3

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 m ...[more]

PMID: 36511390

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Project description:BackgroundNeurometabolic abnormalities and amyloid-beta plaque deposition are important early pathophysiologic changes in Alzheimer's disease (AD). This study investigated the relationship between high-energy phosphorus-containing metabolites, glucose uptake, and amyloid plaque using phosphorus magnetic resonance spectroscopy (31P-MRS) and positron emission tomography (PET).MethodsWe measured 31P-MRS, fluorodeoxyglucose (FDG)-PET, and Pittsburgh Compound B (PiB)-PET in a cohort of 20 cognitively normal middle-aged adults at risk for AD. We assessed 31P-MRS reliability by scanning a separate cohort of 13 healthy volunteers twice each. We calculated the coefficient-of-variation (CV) of metabolite ratios phosphocreatine-to-adenosine triphosphate (PCr/α-ATP), inorganic phosphate (Pi)-to-α-ATP, and phosphomonoesters-to-phosphodiesters (PME/PDE), and pH in pre-defined brain regions. We performed linear regression analysis to determine the relationship between 31P measurements and tracer uptake, and Dunn's multiple comparison tests to investigate regional differences in phosphorus metabolism. Finally, we performed linear regression analysis on 31P-MRS measurements in both cohorts to investigate the relationship of phosphorus metabolism with age.ResultsMost regional 31P metabolite ratio and pH inter- and intra-day CVs were well below 10%. There was an inverse relationship between FDG-SUV levels and metabolite ratios PCr/α-ATP, Pi/α-ATP, and PME/PDE in several brain regions in the AD risk group. There were also several regional differences among 31P metabolites and pH in the AD risk group including elevated PCr/α-ATP, depressed PME/PDE, and elevated pH in the temporal cortices. Increased PCr/α-ATP throughout the brain was associated with aging.ConclusionsPhosphorus spectroscopy in the brain can be performed with high repeatability. Phosphorus metabolism varies with region and age, and is related to glucose uptake in adults at risk for AD. Phosphorus spectroscopy may be a valuable approach to study early changes in brain energetics in high-risk populations.

Dataset Information

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

Publications

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

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