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

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Dounavi, Maria-Eleni  ORCID logo
McKiernan, Elizabeth 
Langsen, Michael 
Muniz-Terrera, Graciela 


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.


Acknowledgements: The views expressed are those of the author(s) and not necessarily those of the NIHR or the Department of Health and Social Care. We thank the PREVENT-Dementia participants and the DeNDRoN specialty within the Clinical Research Network for help with recruitment and participant assessments.

Funder: Cambridge National Institute for Health

Funder: National Institute for Health

Funder: Care Research Biomedical Research Centre

Funder: Imperial College London; DOI:

Funder: Melville Trust PhD studentship

Funder: Sheffield National Institute for Health

Funder: Care Research Biomedical Research Center

Funder: Oxford National Institute for Health

Funder: Medical Research Council; DOI:

Funder: Dementias Platform UK; DOI:

Funder: Care Research fellowships


APOE4, Alzheimer’s disease, MRS, brain metabolism, preclinical dementia

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Brain Commun

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Oxford University Press (OUP)
National Institute for Health and Care Research (IS-BRC-1215-20014)