title: Regional fluorodeoxyglucose metabolism and instrumental activities of daily living across the Alzheimer's disease spectrum.
abstract: BACKGROUND
  Impairment in instrumental activities of daily living (IADL) begins as individuals with amnestic mild cognitive impairment (MCI) transition to Alzheimer's disease (AD) dementia. IADL impairment in AD dementia has been associated with inferior parietal, inferior temporal, and superior occipital hypometabolism using 18F-fluorodeoxyglucose (FDG) positron emission tomography (PET).
  
  
  OBJECTIVE
  To investigate the relationship between regional FDG metabolism and IADL in clinically normal (CN) elderly, MCI, and mild AD dementia subjects cross-sectionally and longitudinally.
  
  
  METHODS
  One hundred and four CN, 203 MCI, and 95 AD dementia subjects from the Alzheimer's Disease Neuroimaging Initiative underwent clinical assessments every 6 to 12 months for up to three years and baseline FDG PET. The subjective, informant-based Functional Activities Questionnaire was used to assess IADL. General linear models and mixed effects models were used, covarying for demographics, cognition, and behavior.
  
  
  RESULTS
  The cross-sectional analysis revealed middle frontal and orbitofrontal hypometabolism were significantly associated with greater IADL impairment. Additionally, the interaction of diagnosis with posterior cingulate and with parahippocampal hypometabolism showed a greater decline in IADL performance as metabolism decreased for the AD dementia relative to the MCI group, and the MCI group relative to the CN group. The longitudinal analysis showed that baseline middle frontal and posterior cingulate hypometabolism were significantly associated with greater rate of increase in IADL impairment over time.
  
  
  CONCLUSIONS
  These results suggest that regional synaptic dysfunction, including the Alzheimer-typical medial parietal and less typical frontal regions, relates to daily functioning decline at baseline and over time across the early AD spectrum.
authors.affiliation: Center for Alzheimer Research and Treatment, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA Department of Neurology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA Department of Neurology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.
authors.forename: Kamolika
authors.initials: K
authors.lastname: Roy
authors.affiliation: Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.
authors.forename: Lesley C
authors.initials: LC
authors.lastname: Pepin
authors.affiliation: Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.
authors.forename: Marlie
authors.initials: M
authors.lastname: Philiossaint
authors.affiliation: Center for Alzheimer Research and Treatment, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA Department of Neurology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA Department of Neurology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.
authors.forename: Natacha
authors.initials: N
authors.lastname: Lorius
authors.affiliation: Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.
authors.forename: J Alex
authors.initials: JA
authors.lastname: Becker
authors.affiliation: Department of Neurology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.
authors.forename: Joseph J
authors.initials: JJ
authors.lastname: Locascio
authors.affiliation: Center for Alzheimer Research and Treatment, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA Department of Neurology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA Department of Neurology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.
authors.forename: Dorene M
authors.initials: DM
authors.lastname: Rentz
authors.affiliation: Center for Alzheimer Research and Treatment, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA Department of Neurology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA Department of Neurology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.
authors.forename: Reisa A
authors.initials: RA
authors.lastname: Sperling
authors.affiliation: Center for Alzheimer Research and Treatment, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA Department of Neurology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA Department of Neurology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA Department of Radiology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.
authors.forename: Keith A
authors.initials: KA
authors.lastname: Johnson
authors.affiliation: Center for Alzheimer Research and Treatment, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA Department of Neurology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA Department of Neurology, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.
authors.forename: Gad A
authors.initials: GA
authors.lastname: Marshall
mesh_terms: D000203:Activities of Daily Living; D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000000981:diagnostic imaging* / Q000378:metabolism; D001921:Brain / Q000000981:diagnostic imaging* / Q000378:metabolism; D001931:Brain Mapping; D060825:Cognitive Dysfunction / Q000000981:diagnostic imaging* / Q000378:metabolism; D003430:Cross-Sectional Studies; D016208:Databases, Factual; D018450:Disease Progression; D005260:Female; D019788:Fluorodeoxyglucose F18; D005500:Follow-Up Studies; D006801:Humans; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D049268:Positron-Emission Tomography; D019275:Radiopharmaceuticals; D011795:Surveys and Questionnaires
chemical_list: D019275:Radiopharmaceuticals; D019788:Fluorodeoxyglucose F18
keywords: $^{18}$F-fluorodeoxyglucose positron emission tomography; Alzheimer's disease; instrumental activities of daily living; mild cognitive impairment