Texture‐based morphometry in relation to apolipoprotein ε4 genotype, ageing and sex in a midlife population

Author:

Dounavi Maria‐Eleni1,Mak Elijah1,Operto Gregory2,Muniz‐Terrera Graciela34,Bridgeman Katie3,Koychev Ivan5,Malhotra Paresh6,Naci Lorina7,Lawlor Brian7,Su Li18,Falcon Carles2,Ritchie Karen9,Ritchie Craig W.3,Gispert Juan Domingo2ORCID,O'Brien John T.1

Affiliation:

1. Department of Psychiatry School of Clinical Medicine, University of Cambridge Cambridge UK

2. Barcelonaβeta Brain Research Center (BBRC), Pasqual Maragall Foundation Barcelona Spain

3. Centre for Dementia Prevention University of Edinburgh Edinburgh UK

4. Heritage College of Osteopathic Medicine Ohio University Athens Ohio USA

5. Department of Psychiatry Oxford University UK

6. Division of Brain Science Imperial College Healthcare NHS Trust UK

7. Institute of Neuroscience, Trinity College Dublin, University of Dublin Ireland

8. Department of Neuroscience University of Sheffield Sheffield UK

9. INSERM and University of Montpellier Montpellier France

Abstract

AbstractBrain atrophy and cortical thinning are typically observed in people with Alzheimer's disease (AD) and, to a lesser extent, in those with mild cognitive impairment. In asymptomatic middle‐aged apolipoprotein ε4 (ΑPOE4) carriers, who are at higher risk of future AD, study reports are discordant with limited evidence of brain structural differences between carriers and non‐carriers of the ε4 allele. Alternative imaging markers with higher sensitivity at the presymptomatic stage, ideally quantified using typically acquired structural MRI scans, would thus be of great benefit for the detection of early disease, disease monitoring and subject stratification. In the present cross‐sectional study, we investigated textural properties of T1‐weighted 3T MRI scans in relation to APOE4 genotype, age and sex. We pooled together data from the PREVENT‐Dementia and ALFA studies focused on midlife healthy populations with dementia risk factors (analysable cohort: 1585 participants; mean age 56.2 ± 7.4 years). Voxel‐based and texture (examined features: contrast, entropy, energy, homogeneity) based morphometry was used to identify areas of volumetric and textural differences between APOE4 carriers and non‐carriers. Textural maps were generated and were subsequently harmonised using voxel‐wise COMBAT. For all analyses, APOE4, sex, age and years of education were used as model predictors. Interactions between APOE4 and age were further examined. There were no group differences in regional brain volume or texture based on APOE4 carriership or when age × APOE4 interactions were examined. Older people tended to have a less homogeneous textural profile in grey and white matter and a more homogeneous profile in the ventricles. A more heterogeneous textural profile was observed for females in areas such as the ventricles, frontal and parietal lobes and for males in the brainstem, cerebellum, precuneus and cingulate. Overall, we have shown the absence of volumetric and textural differences between APOE4 carriers and non‐carriers at midlife and have established associations of textural features with ageing and sex.

Funder

Alzheimer's Society

Alzheimer's Association

NIHR Cambridge Biomedical Research Centre

NIHR Imperial Biomedical Research Centre

Publisher

Wiley

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