title: Tracking cognitive change over 24 weeks with longitudinal functional magnetic resonance imaging in Alzheimer's disease.
abstract: BACKGROUND
  Previous studies have revealed that functional magnetic resonance imaging (fMRI) blood oxygen level-dependent (BOLD) signal in specific brain regions correlates with cross-sectional performance on standardized clinical trial measures in Alzheimer's disease (AD); however, the relationship between longitudinal change in fMRI-BOLD signal and neuropsychological performance remains unknown.
  
  
  OBJECTIVE
  To identify changes in regional fMRI-BOLD activity that tracks change in neuropsychological performance in mild AD dementia over 6 months.
  
  
  METHODS
  Twenty-four subjects (mean age 71.6) with mild AD dementia (mean Mini Mental State Examination 21.7, Global Clinical Dementia Rating 1.0) on stable donepezil dosing participated in two task-related fMRI sessions consisting of a face-name paired associative encoding memory paradigm 24 weeks apart during a randomized placebo-controlled pharmaco-fMRI drug study. Regression analysis was used to identify regions where the change in fMRI activity for Novel > Repeated stimulus contrast was associated with the change scores on postscan memory tests and the Free and Cued Selective Reminding Test (FCSRT).
  
  
  RESULTS
  Correlations between changes in postscan memory accuracy and changes in fMRI activity were observed in regions including the angular gyrus, parahippocampal gyrus, inferior frontal gyrus and cerebellum. Correlations between changes in FCSRT-free recall and changes in fMRI were observed in regions including the inferior parietal lobule, precuneus, hippocampus and parahippocampal gyrus.
  
  
  CONCLUSIONS
  Changes in encoding-related fMRI activity in regions implicated in mnemonic networks correlated with changes in psychometric measures of episodic memory retrieval performed outside the scanner. These exploratory results support the potential of fMRI activity to track cognitive change and detect signals of short-term pharmacologic effect in early-phase AD studies.
authors.affiliation: Department of Neurology, Massachusetts General Hospital, Boston, MA, USA.
authors.forename: Donald G
authors.initials: DG
authors.lastname: McLaren
authors.forename: Aishwarya
authors.initials: A
authors.lastname: Sreenivasan
authors.forename: Eli L
authors.initials: EL
authors.lastname: Diamond
authors.forename: Meghan B
authors.initials: MB
authors.lastname: Mitchell
authors.forename: Koene R A
authors.initials: KR
authors.lastname: Van Dijk
authors.forename: Amy N
authors.initials: AN
authors.lastname: Deluca
authors.forename: Jacqueline L
authors.initials: JL
authors.lastname: O'Brien
authors.forename: Dorene M
authors.initials: DM
authors.lastname: Rentz
authors.forename: Reisa A
authors.initials: RA
authors.lastname: Sperling
authors.forename: Alireza
authors.initials: A
authors.lastname: Atri
mesh_terms: D000368:Aged; D000544:Alzheimer Disease / Q000188:drug therapy / Q000473:pathology* / Q000503:physiopathology*; D001931:Brain Mapping; D003071:Cognition / Q000502:physiology*; D000077265:Donepezil; D015259:Dopamine Agents / Q000627:therapeutic use; D005260:Female; D006801:Humans; D007189:Indans / Q000627:therapeutic use; D008137:Longitudinal Studies; D008279:Magnetic Resonance Imaging; D008297:Male; D008559:Memantine / Q000627:therapeutic use; D009483:Neuropsychological Tests; D018697:Nootropic Agents / Q000627:therapeutic use; D010100:Oxygen / Q000097:blood*; D010880:Piperidines / Q000627:therapeutic use; D012044:Regression Analysis
chemical_list: D015259:Dopamine Agents; D007189:Indans; D018697:Nootropic Agents; D010880:Piperidines; D000077265:Donepezil; D010100:Oxygen; D008559:Memantine