Macrostructural brain alterations at midlife are connected to cardiovascular and not inherited risk of future dementia: the PREVENT-Dementia study

Abstract

Background Macrostructural brain alterations in the form of brain atrophy or cortical thinning typically occur during the prodromal Alzheimer’s disease stage. Mixed findings largely dependent on the age of the examined cohorts have been reported during the preclinical, asymptomatic disease stage. In the present study, our aim was to examine the association of midlife dementia risk with brain macrostructural alterations. Methods Structural 3T MRI scans were acquired for 647 cognitively normal middle-aged (40–59 years old) participants in the PREVENT-Dementia study. Cortical thickness, volumes of subcortical structures, the hippocampus and hippocampal subfields were quantified using Freesurfer version 7.1. The clarity of the hippocampal molecular layer was evaluated based on T2-weighted hippocampal scans. Associations of structural measures with apolipoprotein ε4 (APOE4) genotype and dementia family history (FHD), were investigated using linear regression. Correlations between the CAIDE dementia risk score (incorporating information about blood pressure, cholesterol, physical activity, body mass index, education, age and sex) and structural measures were further investigated. Results A higher CAIDE score was associated with thinner cortex and a larger hippocampal fissure. APOE4 genotype was associated with reduced molecular layer clarity. Conclusions Our findings suggest that a higher CAIDE score is associated with widespread cortical thinning. Conversely, APOE4 carriers and participants with FHD do not demonstrate prominent macrostructural alterations at this age range. These findings indicate that cardiovascular and not inherited risk factors for dementia are associated with macrostructural brain alterations at midlife.

Path integration selectively predicts midlife risk of Alzheimer’s disease

“…Structural MRI using ultra high field 7T did not reveal any associations between PI and volumes of brain regions of interest, even at subfield level. This however is consistent with previous findings in presymptomatic familial AD populations (33) and prior PREVENT imaging studies, which did not identify clear patterns of atrophy (34). Considering our participant age (approximately two decades away from predicted dementia onset), the absence of volumetric change may indicate an absence of regional neurodegeneration in this cohort at this early stage in the disease process.…”

Disrupted role of the connectivity between the locus coeruleus and the hippocampus in cognition of healthy, middle-aged individuals at risk of dementia: the PREVENT-Dementia study

“…Dounavi et al (2020) reported that the volume of the molecular layer of the hippocampus was reduced in cognitively healthy midlife individuals with APOE ε 4 genotype. A more recent study (Dounavi et al, 2022) reported that the hippocampal fissure was enlarged in middle-aged individuals with high CAIDE dementia risk scores. While this accumulating evidence indicates that, individually, the LC and hippocampus are affected in midlife by risk of late-life AD, it remains unknown whether their interactions and joint role in cognition are affected by AD risk at this stage.…”

Modifiable and non-modifiable risk factors of dementia on midlife cerebral small vessel disease in cognitively healthy middle-aged adults: the PREVENT-Dementia study

“…The protocol of the PREVENT-Dementia study has been described in detail previously [ 18 , 19 ]. Briefly, participants were recruited from five sites across the UK and Ireland (West London, Edinburgh, Cambridge, Oxford, Dublin).…”