title: Regional neuronal network failure and cognition in late-onset sporadic Alzheimer disease.
abstract: OBJECTIVE
  The severe cognitive deficits in Alzheimer disease are associated with structural lesions in gray and white matter in addition to changes in synaptic function. The current investigation studied the breakdown of the structure and function in regional networks involving the Papez circuit and extended neocortical association areas.
  
  
  METHODS
  Cortical volumetric and diffusion tensor imaging (3T MR imaging), positron-emission tomography with (18)F fluorodeoxyglucose on a high-resolution research tomograph, and comprehensive neuropsychological assessments were performed in patients with late-onset sporadic Alzheimer disease, those with mild cognitive impairment, and elderly healthy controls.
  
  
  RESULTS
  Atrophy of the medial temporal lobes was the strongest and most consistent abnormality in patients with mild cognitive impairment and Alzheimer disease. Atrophy in the temporal, frontal, and parietal regions was most strongly related to episodic memory deficits, while deficits in semantic cognition were also strongly related to reductions of glucose metabolism in the posterior cingulate cortex and temporoparietal regions. Changes in fractional anisotropy within white matter tracts, particularly in the left cingulum bundle, uncinate fasciculus, superior longitudinal fasciculus, and inferior fronto-occipital fasciculus, were significantly associated with the cognitive deficits in multiple regression analyses. Posterior cingulate and orbitofrontal metabolic deficits appeared to be related to microstructural changes in projecting white matter tracts.
  
  
  CONCLUSIONS
  Many lesioned network components within the Papez circuit and extended neocortical association areas were significantly associated with cognitive dysfunction in both mild cognitive impairment and late-onset sporadic Alzheimer disease. Hippocampal atrophy was the most prominent lesion, with associated impairment of the uncinate and cingulum white matter microstructures and hippocampal and posterior cingulate metabolic impairment.
authors.affiliation: From the Wolfson Molecular Imaging Centre (S.F.C., J.M.A.-R., K.H.)Institute of Population Health, Neuroscience and Aphasia Research Unit (S.F.C., M.A.L.R.)Alzheimer Neurobiology Centre (S.F.C.), Department of Neurobiology, Care Sciences and Society, Karolinska Institutet, Stockholm, Sweden.
authors.forename: S F
authors.initials: SF
authors.lastname: Carter
authors.affiliation: School of Psychological Sciences (K.V.E.).
authors.forename: K V
authors.initials: KV
authors.lastname: Embleton
authors.affiliation: From the Wolfson Molecular Imaging Centre (S.F.C., J.M.A.-R., K.H.).
authors.forename: J M
authors.initials: JM
authors.lastname: Anton-Rodriguez
authors.affiliation: Institute of Brain, Behaviour and Mental Health (A.B., K.H.), University of Manchester, Manchester, UK.
authors.forename: A
authors.initials: A
authors.lastname: Burns
authors.affiliation: Institute of Population Health, Neuroscience and Aphasia Research Unit (S.F.C., M.A.L.R.).
authors.forename: M A L
authors.initials: MA
authors.lastname: Ralph
authors.affiliation: From the Wolfson Molecular Imaging Centre (S.F.C., J.M.A.-R., K.H.)Institute of Brain, Behaviour and Mental Health (A.B., K.H.), University of Manchester, Manchester, UK karl.herholz@manchester.ac.uk.
authors.forename: K
authors.initials: K
authors.lastname: Herholz
mesh_terms: D017668:Age of Onset; D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000000981:diagnostic imaging / Q000378:metabolism / Q000473:pathology; D001921:Brain / Q000000981:diagnostic imaging / Q000378:metabolism / Q000473:pathology; D060825:Cognitive Dysfunction / Q000000981:diagnostic imaging / Q000378:metabolism / Q000473:pathology; D056324:Diffusion Tensor Imaging / Q000379:methods*; D005260:Female; D019788:Fluorodeoxyglucose F18; D006801:Humans; D008297:Male; D008875:Middle Aged; D064847:Multimodal Imaging / Q000379:methods; D009415:Nerve Net / Q000000981:diagnostic imaging / Q000378:metabolism / Q000473:pathology; D009483:Neuropsychological Tests; D049268:Positron-Emission Tomography / Q000379:methods*; D019275:Radiopharmaceuticals
chemical_list: D019275:Radiopharmaceuticals; D019788:Fluorodeoxyglucose F18