Abstract
Abstract Can plasma metabolomics reveal mechanisms of brain aging? We investigated metabolomic signatures of brain atrophy patterns related to cognitive decline and Alzheimer’s disease(AD) risk. Relationships between metabolomics(Biocrates-p500) and annual rates of change in two neuroimaging-based brain atrophy patterns(SPARE-BA indexing brain aging, SPARE-AD indexing AD-related atrophy) were examined using multivariable linear regression in 477 Baltimore Longitudinal Study of Aging participants aged 60+, adjusted for demographic variables and BMI. Higher concentrations of sarcosine, triglycerides, diglycerides, and ceramides and lower concentrations from phosphatidylcholines and cholesteryl ester were associated with faster rates of SPARE-BA increase longitudinally. Higher concentrations of diglyceride and alpha-amino-butyric acid and lower concentrations of tryptophan, hippuric acid, cholesteryl ester, phosphatidylcholine and sphingomyelin were associated with faster rates of SPARE-AD. Metabolites have differential associations with age-related and AD-related brain atrophy patterns, which may provide new insights into preventive and therapeutic interventions. Future studies should examine whether metabolite changes precede brain atrophy patterns.
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