Investigating the Brain's Neurochemical Profile at Midlife in Relation to Dementia Risk Factors

Overview

Journal Brain Commun

Publisher Oxford University Press

Specialty Neurology

Date 2024 May 23

PMID 38779354

Authors

Maria-Eleni Dounavi

Elizabeth McKiernan

Michael Langsen

Sarah Gregory

Graciela Muniz-Terrera

Maria Angeles Prats-Sedano

Marius Ovidiu Mada

Guy B Williams

Brian Lawlor

Lorina Naci

Clare Mackay

Ivan Koychev

Paresh Malhotra

Karen Ritchie

Craig W Ritchie

Li Su

Adam D Waldman

John T O Brien

Affiliations

Soon will be listed here.

Abstract

Changes in the brain's physiology in Alzheimer's disease 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. Participants in the multi-site PREVENT-Dementia study (age range 40-59 year old) underwent 3T magnetic resonance spectroscopy with the spectroscopy voxel placed in the posterior cingulate/precuneus region. Using LCModel, we quantified the absolute concentrations of myo-inositol, total N-acetylaspartate, total creatine, choline, glutathione and glutamate-glutamine 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 magnetic resonance spectroscopy voxel. We investigated how metabolite concentrations related to apolipoprotein ɛ4 genotype, dementia family history, 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). Dementia family history was associated with decreased total N-acetylaspartate and no differences were found between apolipoprotein ɛ4 carriers and non-carriers. A higher Cardiovascular Risk Factors, Aging, and Incidence of Dementia score related to higher myo-inositol, choline, total creatine and glutamate-glutamine, 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 choline, myo-inositol and total creatine; 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.

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