title: Does posterior cingulate hypometabolism result from disconnection or local pathology across preclinical and clinical stages of Alzheimer's disease?
abstract: OBJECTIVE
  Posterior cingulate cortex (PCC) hypometabolism as measured by FDG PET is an indicator of Alzheimer's disease (AD) in prodromal stages, such as in mild cognitive impairment (MCI), and has been found to be closely associated with hippocampus atrophy in AD dementia. We studied the effects of local and remote atrophy and of local amyloid load on the PCC metabolic signal in patients with different preclinical and clinical stages of AD.
  
  
  METHODS
  We determined the volume of the hippocampus and PCC grey matter based on volumetric MRI scans, PCC amyloid load based on AV45 PET, and PCC metabolism based on FDG PET in 667 subjects participating in the Alzheimer's Disease Neuroimaging Initiative spanning the range from cognitively normal ageing through prodromal AD to AD dementia.
  
  
  RESULTS
  In cognitively normal individuals and those with early MCI, PCC hypometabolism was exclusively associated with hippocampus atrophy, whereas in subjects with late MCI it was associated with both local and remote effects of atrophy as well as local amyloid load. In subjects with AD dementia, PCC hypometabolism was exclusively related to local atrophy.
  
  
  CONCLUSIONS
  Our findings suggest that the effects of remote pathology on PCC hypometabolism decrease and the effects of local pathology increase from preclinical to clinical stages of AD, consistent with a progressive disconnection of the PCC from downstream cortical and subcortical brain regions.
authors.affiliation: Department of Psychosomatic Medicine, University of Rostock, Rostock, Germany. stefan.teipel@med.uni-rostock.de.|DZNE, German Center for Neurodegenerative Diseases, Gehlsheimer Str. 20, 18147, Rostock, Germany. stefan.teipel@med.uni-rostock.de.
authors.forename: Stefan
authors.initials: S
authors.lastname: Teipel
authors.affiliation: DZNE, German Center for Neurodegenerative Diseases, Gehlsheimer Str. 20, 18147, Rostock, Germany.
authors.forename: Michel J
authors.initials: MJ
authors.lastname: Grothe
mesh_terms: D000368:Aged; D000375:Aging; D000544:Alzheimer Disease / Q000000981:diagnostic imaging* / Q000378:metabolism* / Q000503:physiopathology; D001284:Atrophy; D003071:Cognition; D060825:Cognitive Dysfunction / Q000000981:diagnostic imaging / Q000378:metabolism / Q000503:physiopathology; D005260:Female; D019788:Fluorodeoxyglucose F18 / Q000737:chemistry; D066128:Gray Matter / Q000000981:diagnostic imaging / Q000473:pathology; D006179:Gyrus Cinguli / Q000378:metabolism* / Q000503:physiopathology; D006624:Hippocampus / Q000000981:diagnostic imaging / Q000473:pathology; D006801:Humans; D007091:Image Processing, Computer-Assisted; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D049268:Positron-Emission Tomography
chemical_list: D019788:Fluorodeoxyglucose F18
keywords: Amyloid pathology; Disconnection; Early diagnosis; Hippocampus atrophy; Multimodal imaging; Prodromal Alzheimer’s disease