Abstract
BackgroundMacrostructural 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.MethodsStructural 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.ResultsA higher CAIDE score was associated with thinner cortex and a larger hippocampal fissure. APOE4 genotype was associated with reduced molecular layer clarity.ConclusionsOur 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.
Highlights
Neurodegeneration, one of the main pathological hallmarks of Alzheimer’s disease (AD), can be evaluated with structural MRI and involves a characteristic pattern of gray matter (GM) atrophy in key temporo-parietal regions [1]
There were no differences in the examined brain volumes between apolipoprotein ε4 (APOE4) carriers and non-carriers or between family history of dementia (FHD)- and FHD+; only the amygdala was slightly larger in FHD+
When controlling for eTIV, the average clarity was associated with the CA1 (ρ = 0.10, p = 0.02, pFDR = 0.05), fissure (ρ = − 0.15, p < 0.01, pFDR < 0.01) and hippocampal tail (ρ = 0.10, p = 0.02, pFDR = 0.05) volumes. In this cohort of middle-aged participants, half with FHD and 39% of whom carry at least one copy of the APOE4 allele, a higher Cardiovascular Risk factors aging and dementia (CAIDE) score was associated with extensive areas of cortical thinning and a higher hippocampal fissure volume
Summary
Neurodegeneration, one of the main pathological hallmarks of Alzheimer’s disease (AD), can be evaluated with structural MRI and involves a characteristic pattern of gray matter (GM) atrophy in key temporo-parietal regions [1]. The majority of studies investigating neurodegeneration with structural MRI have focused on established AD, mild cognitive impairment (MCI) or subjective cognitive decline, with very few studies conducted in the disease’s preclinical stage where participants are cognitively asymptomatic, and most of these have been in older people (65 years or over) [4] These later studies on preclinical AD, especially when focused on young or middle-aged participants, do not normally include information on disease progression, since this would take many years, even decades. 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
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
