METABOLOMIC SIGNATURES OF BRAIN ATROPHY PATTERNS IN AGING AND ALZHEIMER'S DISEASE

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.