Gray matter network associated with risk for Alzheimer's disease in young to middle-aged adults

Abstract

The apolipoprotein E (APOE) ε4 allele increases the risk for late-onset Alzheimer's disease (AD) and age-related cognitive decline. We investigated whether ε4 carriers show reductions in gray matter volume compared to ε4 non-carriers decades prior to the potential onset of AD dementia or healthy cognitive aging. Fourteen cognitively normal ε4 carriers, ages 26 to 45, were compared with 10 age-matched, ε4 non-carriers using T1-weighted volumetric magnetic resonance imaging (MRI) scans. All had reported first or second-degree family histories of dementia. Group differences in gray matter were tested using voxel-based morphometry (VBM) and a multivariate model of regional covariance, the Scaled Subprofile Model (SSM). A combination of the first two SSM MRI gray matter patterns distinguished the APOE ε4 carriers from non-carriers. This combined pattern showed gray matter reductions in bilateral dorsolateral and medial frontal, anterior cingulate, parietal, and lateral temporal cortices with co-varying relative increases in cerebellum, occipital, fusiform, and hippocampal regions. With these gray matter differences occurring decades prior to the potential onset of dementia or cognitive aging, the results suggest longstanding, gene-associated differences in brain morphology that may lead to preferential vulnerability for the later effects of late onset AD or healthy brain aging.

Imaging structural co-variance between human brain regions

“…Even in the healthy ageing population, regional brain atrophy is linked to the deposition of the Alzheimer’s disease-related protein amyloid-β, and the focus of this amyloid-related atrophy is part of a structural co-variance network that is associated with cognitive functioning 137 . Similar patterns of grey matter loss within networks of brain regions with high structural correlations can also be distinguished in cognitively normal young adults who are genetically at risk of developing Alzheimer’s disease 138 . The fact that atrophy occurs within structural co-variance networks both highlights their functional significance in healthy individuals and supports network interpretations of neurodegenerative disease.…”

Exercise, APOE genotype, and the evolution of the human lifespan

“…In this case, reductions in cerebral glucose metabolism revealed by positron emission tomography (PET) imaging in young to late middle-aged adults have been most consistently observed in brain areas typically affected in AD, including parietotemporal and frontal brain regions, along with indications of increased fibrillar amyloid deposition with PET [45–48]. Using magnetic resonance imaging (MRI) scans in young to late middle-aged and older adults, alterations in regional cerebral activity during cognitive task performance and brain network connectivity, as well as reductions and declines in structural gray matter volume and cortical thickness, have also been reported in asymptomatic ε4 carriers compared with noncarriers [49–58]. However, these MRI structural, functional, and network connectivity effects have been less consistently observed across different-aged samples and methods [54,57,59–61].…”

Classification of Alzheimer Disease Based on Structural Magnetic Resonance Imaging by Kernel Support Vector Machine Decision Tree

“…100 of the included subjects were clinically diagnosed with very mild to moderate Alzheimer's disease [13]. [14,15]. The brain extraction tool (BET) [16] was employed removing facial features (http://fsl.fmrib.ox.ac.uk/fsl/fslwiki/BET).…”