TY - JOUR
T1 - Investigating the brain's neurochemical profile at midlife in relation to dementia risk factors
AU - Dounavi, Maria-Eleni
AU - McKiernan, Elizabeth
AU - Langsen, Michael
AU - Gregory, Sarah
AU - Muniz-Terrera, Graciela
AU - Prats-Sedano, Maria Angeles
AU - Mada, Marius Ovidiu
AU - Williams, Guy B.
AU - Lawlor, Brian
AU - Naci, Lorina
AU - Mackay, Clare
AU - Koychev, Ivan
AU - Malhotra, Paresh
AU - Ritchie, Karen
AU - Ritchie, Craig W.
AU - Su, Li
AU - Waldman, Adam D.
AU - O' Brien, John T.
N1 - Funding: This study was funded by project grants from Alzheimer’s Society (grant numbers 178 and 264), Alzheimer’s Association (grant number TriBEKa-17–519007), philanthropic donations and supported by the National Institute for Health and Care Research (NIHR) Cambridge Biomedical Research Centre (BRC-1215-20014) and the NIHR Imperial Biomedical Research Centre . EM is funded by Alzheimer’s Society (AS-CTF-17b-003). ML is supported by a Melville Charitable Trust PhD studentship. LS is supported by the NIHR Sheffield Biomedical Research Center, Alzheimer’s Research UK (ARUK-SRF2017B-1) and Lewy Body Society (LS002/2019). IK is supported by the NIHR Oxford Biomedical Research Center, Medical Research Council, a Dementias Platform UK grant and personal National Institute for Health and Care Research fellowships.
PY - 2024/5/3
Y1 - 2024/5/3
N2 - 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.
AB - 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.
KW - Apoe4
KW - Alzheimer's disease
KW - Mrs
KW - Brain metabolism
KW - Preclinical dementia
U2 - 10.1093/braincomms/fcae138
DO - 10.1093/braincomms/fcae138
M3 - Article
C2 - 38779354
SN - 2632-1297
VL - 6
SP - 1
EP - 13
JO - Brain Communications
JF - Brain Communications
IS - 3
M1 - fcae138
ER -