title: A Multimodal Structural and Functional Neuroimaging Study of Amnestic Mild Cognitive Impairment.
abstract: Examination of brain structural and functional abnormalities in amnestic mild cognitive impairment (aMCI) has the potential to enhance our understanding of the initial pathophysiological changes in dementia. We examined gray matter volumes and white matter microstructural integrity, as well as resting state functional connectivity (rsFC) in patients with aMCI (N = 48) in comparison to elderly cognitively healthy comparison subjects (N = 48). Brain volumetric comparisons were carried out using voxel-based morphometric analysis of T1-weighted images using the FMRIB Software Library. White matter microstructural integrity was examined using whole-brain tract-based spatial statistics analysis of fractional anisotropy maps generated from diffusion tensor imaging data. Finally, rsFC differences between the samples were examined by Multivariate Exploratory Linear Optimised Decomposition into Independent Components of the resting state functional magnetic resonance imaging time series, followed by between-group comparisons of selected networks using dual regression analysis. Patients with aMCI showed significant gray matter volumetric reductions in bilateral parahippocampal gyri as well as multiple other brain regions including frontal, temporal, and parietal cortices. Additionally, reduced rsFC in the anterior subdivision of the default mode network (DMN) and increased rsFC in the executive network were noted in the absence of demonstrable impairment of white matter microstructural integrity. We conclude that the demonstrable neuroimaging findings in aMCI include significant gray matter volumetric reductions in the fronto-temporo-parietal structures as well as resting state functional connectivity disturbances in DMN and executive network. These findings differentiate aMCI from healthy aging and could constitute the earliest demonstrable neuroimaging findings of incipient dementia.
authors.affiliation: Department of Psychiatry, National Institute of Mental Health and Neurosciences, Bangalore, Karnataka, India; Geriatric Clinic and Services, National Institute of Mental Health and Neurosciences, Bangalore, Karnataka, India.
authors.forename: Srikala
authors.initials: S
authors.lastname: Bharath
authors.affiliation: Department of Psychiatry, National Institute of Mental Health and Neurosciences, Bangalore, Karnataka, India; Multimodal Brain Image Analysis Laboratory, National Institute of Mental Health and Neurosciences, Bangalore, Karnataka, India; Geriatric Clinic and Services, National Institute of Mental Health and Neurosciences, Bangalore, Karnataka, India.
authors.forename: Himanshu
authors.initials: H
authors.lastname: Joshi
authors.affiliation: Department of Psychiatry, National Institute of Mental Health and Neurosciences, Bangalore, Karnataka, India; Multimodal Brain Image Analysis Laboratory, National Institute of Mental Health and Neurosciences, Bangalore, Karnataka, India; Geriatric Clinic and Services, National Institute of Mental Health and Neurosciences, Bangalore, Karnataka, India. Electronic address: jpjnimhans@gmail.com.
authors.forename: John P
authors.initials: JP
authors.lastname: John
authors.affiliation: Department of Clinical Neuroscience, National Institute of Mental Health and Neurosciences, Bangalore, Karnataka, India; Multimodal Brain Image Analysis Laboratory, National Institute of Mental Health and Neurosciences, Bangalore, Karnataka, India; Geriatric Clinic and Services, National Institute of Mental Health and Neurosciences, Bangalore, Karnataka, India.
authors.forename: Rakesh
authors.initials: R
authors.lastname: Balachandar
authors.affiliation: Department of Psychiatry, National Institute of Mental Health and Neurosciences, Bangalore, Karnataka, India; Geriatric Clinic and Services, National Institute of Mental Health and Neurosciences, Bangalore, Karnataka, India.
authors.forename: Shilpa
authors.initials: S
authors.lastname: Sadanand
authors.affiliation: Department of Neuroimaging and Interventional Radiology, National Institute of Mental Health and Neurosciences, Bangalore, Karnataka, India.
authors.forename: Jitendra
authors.initials: J
authors.lastname: Saini
authors.affiliation: Department of Clinical Psychology, National Institute of Mental Health and Neurosciences, Bangalore, Karnataka, India; Geriatric Clinic and Services, National Institute of Mental Health and Neurosciences, Bangalore, Karnataka, India.
authors.forename: Keshav J
authors.initials: KJ
authors.lastname: Kumar
authors.affiliation: Department of Psychiatry, National Institute of Mental Health and Neurosciences, Bangalore, Karnataka, India; Geriatric Clinic and Services, National Institute of Mental Health and Neurosciences, Bangalore, Karnataka, India.
authors.forename: Mathew
authors.initials: M
authors.lastname: Varghese
mesh_terms: D000368:Aged; D016880:Anisotropy; D001931:Brain Mapping; D016022:Case-Control Studies; D060825:Cognitive Dysfunction / Q000000981:diagnostic imaging*; D056324:Diffusion Tensor Imaging; D005260:Female; D059907:Functional Neuroimaging; D066128:Gray Matter / Q000000981:diagnostic imaging / Q000473:pathology*; D006801:Humans; D007194:India; D016014:Linear Models; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D066127:White Matter / Q000000981:diagnostic imaging / Q000473:pathology*
keywords: Alzheimer's disease; dementia; diffusion tensor imaging (DTI); functional magnetic resonance imaging (fMRI); independent component analysis (ICA); tract-based spatial statistics (TBSS)