title: Cognitive Correlates of Basal Forebrain Atrophy and Associated Cortical Hypometabolism in Mild Cognitive Impairment.
abstract: Degeneration of basal forebrain (BF) cholinergic nuclei is associated with cognitive decline, and this effect is believed to be mediated by neuronal dysfunction in the denervated cortical areas. MRI-based measurements of BF atrophy are increasingly being used as in vivo surrogate markers for cholinergic degeneration, but the functional implications of reductions in BF volume are not well understood. We used high-resolution MRI, fluorodeoxyglucose-positron emission tomography (PET), and neuropsychological test data of 132 subjects with mild cognitive impairment (MCI) and 177 cognitively normal controls to determine associations between BF atrophy, cortical hypometabolism, and cognitive deficits. BF atrophy in MCI correlated with both impaired memory function and attentional control deficits, whereas hippocampus volume was more specifically associated with memory deficits. BF atrophy was also associated with widespread cortical hypometabolism, and path analytic models indicated that hypometabolism in domain-specific cortical networks mediated the association between BF volume and cognitive dysfunction. The presence of cortical amyloid pathology, as assessed using AV45-PET, did not significantly interact with the observed associations. These data underline the potential of multimodal imaging markers to study structure-function-cognition relationships in the living human brain and provide important in vivo evidence for an involvement of the human BF in cortical activity and cognitive function.
authors.affiliation: German Center for Neurodegenerative Diseases (DZNE), Rostock, Germany.
authors.forename: Michel J
authors.initials: MJ
authors.lastname: Grothe
authors.affiliation: Laboratory of Morphological Brain Research, Department of Psychiatry, University of Würzburg, Würzburg, Germany.
authors.forename: Helmut
authors.initials: H
authors.lastname: Heinsen
authors.affiliation: Department of Radiology.
authors.forename: Edson
authors.initials: E
authors.lastname: Amaro
authors.affiliation: Aging Brain Study Group, LIM-22, Department of Pathology, University of Sao Paulo Medical School, Sao Paulo, Brazil.|UCSF Memory and Aging Center, University of California - San Francisco, San Francisco, CA, USA.
authors.forename: Lea T
authors.initials: LT
authors.lastname: Grinberg
authors.affiliation: German Center for Neurodegenerative Diseases (DZNE), Rostock, Germany.|Department of Psychosomatic Medicine, University of Rostock, Rostock, Germany.
authors.forename: Stefan J
authors.initials: SJ
authors.lastname: Teipel
mesh_terms: D000368:Aged; D000682:Amyloid / Q000378:metabolism; D001284:Atrophy; D001921:Brain / Q000000981:diagnostic imaging* / Q000378:metabolism* / Q000473:pathology; D003071:Cognition / Q000502:physiology*; D060825:Cognitive Dysfunction / Q000000981:diagnostic imaging* / Q000378:metabolism* / Q000523:psychology; D005260:Female; D019788:Fluorodeoxyglucose F18; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D008609:Mental Status Schedule; D009483:Neuropsychological Tests; D009929:Organ Size; D049268:Positron-Emission Tomography; D019275:Radiopharmaceuticals; D012720:Severity of Illness Index; D012815:Signal Processing, Computer-Assisted
chemical_list: D000682:Amyloid; D019275:Radiopharmaceuticals; D019788:Fluorodeoxyglucose F18
keywords: AV45-PET; Alzheimer's disease; FDG-PET; MRI; cholinergic degeneration; nucleus basalis Meynert; substantia innominata
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