title: Regional functional connectivity predicts distinct cognitive impairments in Alzheimer's disease spectrum.
abstract: Understanding neural network dysfunction in neurodegenerative disease is imperative to effectively develop network-modulating therapies. In Alzheimer's disease (AD), cognitive decline associates with deficits in resting-state functional connectivity of diffuse brain networks. The goal of the current study was to test whether specific cognitive impairments in AD spectrum correlate with reduced functional connectivity of distinct brain regions. We recorded resting-state functional connectivity of alpha-band activity in 27 patients with AD spectrum--22 patients with probable AD (5 logopenic variant primary progressive aphasia, 7 posterior cortical atrophy, and 10 early-onset amnestic/dysexecutive AD) and 5 patients with mild cognitive impairment due to AD. We used magnetoencephalographic imaging (MEGI) to perform an unbiased search for regions where patterns of functional connectivity correlated with disease severity and cognitive performance. Functional connectivity measured the strength of coherence between a given region and the rest of the brain. Decreased neural connectivity of multiple brain regions including the right posterior perisylvian region and left middle frontal cortex correlated with a higher degree of disease severity. Deficits in executive control and episodic memory correlated with reduced functional connectivity of the left frontal cortex, whereas visuospatial impairments correlated with reduced functional connectivity of the left inferior parietal cortex. Our findings indicate that reductions in region-specific alpha-band resting-state functional connectivity are strongly correlated with, and might contribute to, specific cognitive deficits in AD spectrum. In the future, MEGI functional connectivity could be an important biomarker to map and follow defective networks in the early stages of AD.
authors.affiliation: Memory and Aging Center, Department of Neurology, University of California San Francisco, San Francisco, CA 94158, USA.
authors.forename: Kamalini G
authors.initials: KG
authors.lastname: Ranasinghe
authors.affiliation: Department of Radiology and Biomedical Imaging, Biomagnetic Imaging Laboratory, University of California San Francisco, San Francisco, CA 94143, USA.
authors.forename: Leighton B
authors.initials: LB
authors.lastname: Hinkley
authors.affiliation: Memory and Aging Center, Department of Neurology, University of California San Francisco, San Francisco, CA 94158, USA.
authors.forename: Alexander J
authors.initials: AJ
authors.lastname: Beagle
authors.affiliation: Department of Radiology and Biomedical Imaging, Biomagnetic Imaging Laboratory, University of California San Francisco, San Francisco, CA 94143, USA.
authors.forename: Danielle
authors.initials: D
authors.lastname: Mizuiri
authors.affiliation: Department of Radiology and Biomedical Imaging, Biomagnetic Imaging Laboratory, University of California San Francisco, San Francisco, CA 94143, USA.
authors.forename: Anne F
authors.initials: AF
authors.lastname: Dowling
authors.affiliation: Department of Radiology and Biomedical Imaging, Biomagnetic Imaging Laboratory, University of California San Francisco, San Francisco, CA 94143, USA.
authors.forename: Susanne M
authors.initials: SM
authors.lastname: Honma
authors.affiliation: Gladstone Institute of Neurological Disease, San Francisco, CA 94158, USA.
authors.forename: Mariel M
authors.initials: MM
authors.lastname: Finucane
authors.affiliation: Memory and Aging Center, Department of Neurology, University of California San Francisco, San Francisco, CA 94158, USA.
authors.forename: Carole
authors.initials: C
authors.lastname: Scherling
authors.affiliation: Memory and Aging Center, Department of Neurology, University of California San Francisco, San Francisco, CA 94158, USA.
authors.forename: Bruce L
authors.initials: BL
authors.lastname: Miller
authors.affiliation: Department of Radiology and Biomedical Imaging, Biomagnetic Imaging Laboratory, University of California San Francisco, San Francisco, CA 94143, USA.
authors.forename: Srikantan S
authors.initials: SS
authors.lastname: Nagarajan
authors.affiliation: Memory and Aging Center, Department of Neurology, University of California San Francisco, San Francisco, CA 94158, USA ; Gladstone Institute of Neurological Disease, San Francisco, CA 94158, USA.
authors.forename: Keith A
authors.initials: KA
authors.lastname: Vossel
mesh_terms: D000368:Aged; D000544:Alzheimer Disease / Q000150:complications / Q000175:diagnosis / Q000503:physiopathology*; D001921:Brain / Q000503:physiopathology*; D003072:Cognition Disorders / Q000175:diagnosis / Q000209:etiology / Q000503:physiopathology*; D005260:Female; D006801:Humans; D007090:Image Interpretation, Computer-Assisted; D008279:Magnetic Resonance Imaging; D015225:Magnetoencephalography; D008297:Male; D008875:Middle Aged; D009434:Neural Pathways / Q000503:physiopathology*; D009483:Neuropsychological Tests; D012815:Signal Processing, Computer-Assisted
keywords: Alzheimer’s disease spectrum; CDR-SOB, Clinical Dementia Rating Sum of Boxes; CVLT, California Verbal Learning Test; Logopenic variant PPA; MCI, mild cognitive impairment; MEGI, magnetoencephalographic imaging; MMSE, Mini-Mental State Exam; Magnetoencephalography (MEG); Network dysfunction; PCA, posterior cortical atrophy; Posterior cortical atrophy; Resting-state functional connectivity; VOSP, Visual Object and Space Perception; fMRI, functional magnetic resonance imaging; lvPPA, logopenic variant primary progressive aphasia