Investigating the brain’s neurochemical profile at midlife in relation to dementia risk factors

Abstract

Changes in the brain’s physiology in Alzheimer’s disease (AD) are thought to occur early in the disease’s trajectory. In this study our aim was to investigate the brain’s neurochemical profile in a midlife cohort in relation to risk factors for future dementia using single voxel proton magnetic resonance spectroscopy (MRS). Participants in the multi-site PREVENT-Dementia study (age range 40-59 year old) underwent 3T MRS with the spectroscopy voxel placed in the posterior cingulate/precuneus region. Using LCModel, we quantified the absolute concentrations of myo-inositol (mI), total N-acetylaspartate (tNAA), total creatine (tCr), choline (Cho), glutathione (GSH) and glutamate-glutamine (Glx) for 406 participants (mean age 51.1; 65.3% female). Underlying partial volume effects were accounted for by applying a correction for the presence of cerebrospinal fluid in the MRS voxel. We investigated how metabolite concentrations related to apolipoprotein ε4 (APOE4) genotype, dementia family history (FHD), a risk score (Cardiovascular Risk Factors, Aging and Incidence of Dementia -CAIDE) for future dementia including non-modifiable and potentially-modifiable factors and dietary patterns (adherence to Mediterranean diet). FHD was associated with decreased tNAA and no differences were found between APOE4 carriers and non-carriers. A higher CAIDE score related to higher mI, Cho, tCr and Glx, an effect which was mainly driven by older age and a higher body mass index. Greater adherence to the Mediterranean diet was associated with lower Cho, mI and tCr; these effects did not survive correction for multiple comparisons. The observed associations suggest that at midlife the brain demonstrates subtle neurochemical changes in relation to both inherited and potentially-modifiable risk factors for future dementia.