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In this study our aim was to investigate the brain\u2019s 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\u201359 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 \u025b4 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 \u025b4 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.<\/jats:p>","DOI":"10.1093\/braincomms\/fcae138","type":"journal-article","created":{"date-parts":[[2024,4,17]],"date-time":"2024-04-17T20:02:02Z","timestamp":1713384122000},"source":"Crossref","is-referenced-by-count":2,"title":["Investigating the brain\u2019s neurochemical profile at midlife in relation to dementia risk factors"],"prefix":"10.1093","volume":"6","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8287-346X","authenticated-orcid":false,"given":"Maria-Eleni","family":"Dounavi","sequence":"first","affiliation":[{"name":"Department of Psychiatry, School of Clinical Medicine, University of Cambridge , Cambridge, CB2 0SP , UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Elizabeth","family":"McKiernan","sequence":"additional","affiliation":[{"name":"Department of Psychiatry, School of Clinical Medicine, University of Cambridge , Cambridge, CB2 0SP , UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michael","family":"Langsen","sequence":"additional","affiliation":[{"name":"Center for Clinical Brain Sciences, University of Edinburgh , Edinburgh, EH16 4SB , UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9864-8240","authenticated-orcid":false,"given":"Sarah","family":"Gregory","sequence":"additional","affiliation":[{"name":"Centre for Dementia Prevention, University of Edinburgh , Edinburgh, EH16 4UX , UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Graciela","family":"Muniz-Terrera","sequence":"additional","affiliation":[{"name":"Centre for Dementia Prevention, University of Edinburgh , Edinburgh, EH16 4UX , UK"},{"name":"Heritage College of Osteopathic Medicine, Ohio University , Athens, OH 45701 , USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Maria Angeles","family":"Prats-Sedano","sequence":"additional","affiliation":[{"name":"Department of Psychiatry, School of Clinical Medicine, University of Cambridge , Cambridge, CB2 0SP , UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marius Ovidiu","family":"Mada","sequence":"additional","affiliation":[{"name":"Medical Research Council Cognition and Brain Sciences Unit, University of Cambridge , Cambridge, CB2 7EF , UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Guy B","family":"Williams","sequence":"additional","affiliation":[{"name":"Department of Clinical Neurosciences and Wolfson Brain Imaging Centre, University of Cambridge , Cambridge, CB2 0QQ , UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Brian","family":"Lawlor","sequence":"additional","affiliation":[{"name":"Institute of Neuroscience, Trinity College Dublin, University of Dublin , Dublin, D02 PX31 , Ireland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lorina","family":"Naci","sequence":"additional","affiliation":[{"name":"Institute of Neuroscience, Trinity College Dublin, University of Dublin , Dublin, D02 PX31 , Ireland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6111-8318","authenticated-orcid":false,"given":"Clare","family":"Mackay","sequence":"additional","affiliation":[{"name":"Department of Psychiatry, Oxford University , Oxford, OX3 7JX , UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6813-8493","authenticated-orcid":false,"given":"Ivan","family":"Koychev","sequence":"additional","affiliation":[{"name":"Department of Psychiatry, Oxford University , Oxford, OX3 7JX , UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1897-0780","authenticated-orcid":false,"given":"Paresh","family":"Malhotra","sequence":"additional","affiliation":[{"name":"Department of Brain Sciences, Imperial College Healthcare NHS Trust , London, W12 0NN , UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Karen","family":"Ritchie","sequence":"additional","affiliation":[{"name":"INM, Univ Montpellier, INSERM , Montpellier, 34090 , France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Craig W","family":"Ritchie","sequence":"additional","affiliation":[{"name":"Centre for Dementia Prevention, University of Edinburgh , Edinburgh, EH16 4UX , UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Li","family":"Su","sequence":"additional","affiliation":[{"name":"Department of Psychiatry, School of Clinical Medicine, University of Cambridge , Cambridge, CB2 0SP , UK"},{"name":"Sheffield 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