Higher midlife CAIDE score is associated with increased brain atrophy in a cohort of cognitively healthy middle-aged individuals

Abstract

Background Structural brain changes associated with Alzheimer’s disease (AD) can occur decades before the onset of symptoms. The Cardiovascular Risk Factors, Aging, and Dementia (CAIDE) score has been suggested to be associated with accelerated brain atrophy in middle-aged subjects but the regional specificity of atrophic areas remains to be elucidated. Methods 3T T1-weighted magnetic resonance imaging scans of 160 cognitively healthy middle-aged participants (mean age = 52) in the PREVENT-Dementia cohort, from baseline and from follow-up after 2 years, were examined. Images were preprocessed using Computational Anatomy Toolbox 12. Voxel-based morphometry was performed in FSL 6.0.1 to identify areas of grey matter (GM) volume differences both cross-sectionally and longitudinally between subjects with high and low baseline CAIDE score (CAIDE score was dichotomized at cohort-median). A GM percentage of change map was created for each subject for evaluation of atrophy over 2 years. Analyses were adjusted for age, gender, education and total intracranial volume. Results Compared to subjects with CAIDE score ≤ 6 (low risk), subjects with CAIDE score > 6 (high risk) showed lower GM volume in the temporal, occipital, and fusiform cortex and lingual gyrus at baseline, and greater percentage of GM loss over 2 years in the supramarginal gyrus, angular gyrus, precuneus, lateral occipital cortex, superior parietal lobule and cingulate gyrus (corrected P < 0.05). Conclusion This study demonstrated accelerated GM atrophy concentrated in several AD signature cortical regions in healthy middle-aged subjects with high CAIDE scores.

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

“…Several of the areas where CAIDE and cortical thickness were negatively associated are areas typically associated with the prodromal AD signature pattern [ 45 ]. In PREVENT-Dementia using data from one study site and a binarized CAIDE score (incorporating APOE4), we have found evidence of longitudinal and established atrophy as well as longitudinal ventricular enlargement [ 46 , 47 ]. Similar findings regarding CAIDE and thickness have previously been reported, in the presence though of hippocampal and GM atrophy [ 48 ].…”

Modifiable lifestyle activities affect cognition in cognitively healthy middle-aged individuals at risk for late-life Alzheimer’s Disease

“…Amongst them, the Cardiovascular Risk Factors Aging and Dementia (CAIDE) score has been optimized for middle-aged populations [15] and has been validated in a large US population followed longitudinally over 40 years [16]. Our group's previously reported findings from cognitively healthy middle-aged participants have related these three risk factors to a range of structural and functional brain changes, including APOE 4 genotype to loss of volume in the hippocampal molecular layer [17], and to cerebral hyperperfusion [18][19]; FH to volumetric alterations in hippocampal subfields and to disrupted white matter integrity [18,20]; and, CAIDE to whole brain atrophy [21][22][23] and to hippocampal volume loss [20,23]. APOE 4, FH and CAIDE have also been found to impact cognition in mid-life.…”

“…The PREVENT Dementia Program [25] initiated in 2013, is a prospective study of the cognitively healthy middle-aged children of persons with dementia, designed to seek out clinical and biological changes, which may subsequently be used as short-term outcome measures for midlife secondary preventions. Studies of this and other similar cohorts of cognitively healthy midlife individuals have related these three risk factors to a range of structural and functional brain changes, including APOE □ 4 genotype to loss of volume in the hippocampal molecular layer [26], cerebral hyperperfusion [27-28], reduced grey matter volume in the right hippocampus, precentral gyrus, and cerebellar cortex [29], and to decreased cortical thickness in the frontal cortex [30]; FH to volumetric alterations in hippocampal subfields and to disrupted white matter integrity [27, 31]; and, CAIDE to whole brain atrophy [32-34] and to hippocampal volume loss [31, 34]. All three risk groups have also been found to impact cognition in mid-life.…”

Fluid-attenuated inversion recovery magnetic resonance imaging textural features as sensitive markers of white matter damage in midlife adults

“…In this same cohort, previous analysis using the T 1 -weighted images suggested limited areas of atrophy in subjects with a higher CAIDE. 40 In the past, it has been shown that entropy and contrast of T 1 images relate to tau burden in the neocortex. 41 A further analysis with cardiovascular risk factors, age and sex as predictors unveiled that females had a different textural profile compared with males in both WMH (more heterogeneous textural profile) and NAWM (less heterogeneous), with ageing mainly related to textural alterations in NAWM (more heterogeneous).…”