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Genetic and environmental influences on cortical mean diffusivity.

ABSTRACT: Magnetic resonance imaging (MRI) has become an important tool in the early detection of age-related and neuropathological brain changes. Recent studies suggest that changes in mean diffusivity (MD) of cortical gray matter derived from diffusion MRI scans may be useful in detecting early effects of Alzheimer's disease (AD), and that these changes may be detected earlier than alterations associated with standard structural MRI measures such as cortical thickness. Thus, due to its potential clinical relevance, we examined the genetic and environmental influences on cortical MD in middle-aged men to provide support for the biological relevance of this measure and to guide future gene association studies. It is not clear whether individual differences in cortical MD reflect neuroanatomical variability similarly detected by other MRI measures, or whether unique features are captured. For instance, variability in cortical MD may reflect morphological variability more commonly measured by cortical thickness. Differences among individuals in cortical MD may also arise from breakdowns in myelinated fibers running through the cortical mantle. Thus, we investigated whether genetic influences on variation in cortical MD are the same or different from those influencing cortical thickness and MD of white matter (WM) subjacent to the cortical ribbon. Univariate twin analyses indicated that cortical MD is heritable in the majority of brain regions; the average of regional heritability estimates ranged from 0.38 in the cingulate cortex to 0.66 in the occipital cortex, consistent with the heritability of other MRI measures of the brain. Trivariate analyses found that, while there was some shared genetic variance between cortical MD and each of the other two measures, this overlap was not complete (i.e., the correlation was statistically different from 1). A significant amount of distinct genetic variance influences inter-individual variability in cortical MD; therefore, this measure could be useful for further investigation in studies of neurodegenerative diseases and gene association studies.

SUBMITTER: Elman JA

PROVIDER: S-EPMC5322245 | biostudies-literature | 2017 Feb

REPOSITORIES: biostudies-literature

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Genetic and environmental influences on cortical mean diffusivity.

Elman Jeremy A JA Panizzon Matthew S MS Hagler Donald J DJ Fennema-Notestine Christine C Eyler Lisa T LT Gillespie Nathan A NA Neale Michael C MC Lyons Michael J MJ Franz Carol E CE McEvoy Linda K LK Dale Anders M AM Kremen William S WS

NeuroImage 20161115

Magnetic resonance imaging (MRI) has become an important tool in the early detection of age-related and neuropathological brain changes. Recent studies suggest that changes in mean diffusivity (MD) of cortical gray matter derived from diffusion MRI scans may be useful in detecting early effects of Alzheimer's disease (AD), and that these changes may be detected earlier than alterations associated with standard structural MRI measures such as cortical thickness. Thus, due to its potential clinica ...[more]

PMID: 27864081

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Project description:BACKGROUND:There is increasing interest in improving understanding of the timing and nature of early neurodegeneration in Alzheimer's disease (AD) and developing methods to measure this in vivo. Autosomal dominant familial Alzheimer's disease (FAD) provides the opportunity for investigation of presymptomatic change. We assessed early microstructural breakdown of cortical grey matter in FAD with diffusion-weighted MRI. METHODS:Diffusion-weighted and T1-weighed MRI were acquired in 38 FAD mutation carriers (17 symptomatic, 21 presymptomatic) and 39 controls. Mean diffusivity (MD) was calculated for six cortical regions previously identified as being particularly vulnerable to FAD-related neurodegeneration. Linear regression compared MD between symptomatic and presymptomatic carriers and controls, adjusting for age and sex. Spearman coefficients assessed associations between cortical MD and cortical thickness. Spearman coefficients also assessed associations between cortical MD and estimated years to/from onset (EYO). Across mutation carriers, linear regression assessed associations between MD and EYO, adjusting for cortical thickness. RESULTS:Compared with controls, cortical MD was higher in symptomatic mutation carriers (mean?±?SD CDR?=?0.88?±?0.39) for all six regions (p?<?0.001). In late presymptomatic carriers (within 8.1?years of predicted symptom onset), MD was higher in the precuneus (p?=?0.04) and inferior parietal cortex (p?=?0.003) compared with controls. Across all presymptomatic carriers, MD in the precuneus correlated with EYO (p?=?0.04). Across all mutation carriers, there was strong evidence (p?<?0.001) of association between MD and cortical thickness in all regions except entorhinal cortex. After adjusting for cortical thickness, there remained an association (p?<?0.05) in mutation carriers between MD and EYO in all regions except entorhinal cortex. CONCLUSIONS:Cortical MD measurement detects microstructural breakdown in presymptomatic FAD and correlates with proximity to symptom onset independently of cortical thickness. Cortical MD may thus be a feasible biomarker of early AD-related neurodegeneration, offering additional/complementary information to conventional MRI measures.

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Genetic and environmental influences on cortical mean diffusivity.

Publications

Genetic and environmental influences on cortical mean diffusivity.

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