title: Default mode network connectivity in stable vs progressive mild cognitive impairment.
abstract: OBJECTIVE
  Dysfunction of the default mode network (DMN) has been identified in prior cross-sectional fMRI studies of Alzheimer disease (AD) and mild cognitive impairment (MCI); however, no studies have examined its utility in predicting future cognitive decline.
  
  
  METHODS
  fMRI scans during a face-name memory task were acquired from a cohort of 68 subjects (25 normal control, 31 MCI, and 12 AD). Subjects with MCI were followed for 2.4 years (±0.8) to determine progression to AD. Maps of DMN connectivity were compared with a template DMN map constructed from elderly normal controls to obtain goodness-of-fit (GOF) indices of DMN expression. Indices were compared between groups and correlated with cognitive decline.
  
  
  RESULTS
  GOF indices were highest in normal controls, intermediate in MCI, and lowest in AD (p < 0.0001). In a predictive model (that included baseline GOF indices, age, education, Mini-Mental State Examination score, and an index of DMN gray matter volume), the effect of GOF index on progression from MCI to dementia was significant. In MCI, baseline GOF indices were correlated with change from baseline in functional status (Clinical Dementia Rating-sum of boxes) (r = -0.40, p < 0.04). However, there was no additional predictive value for DMN connectivity when baseline delayed recall was included in the models.
  
  
  CONCLUSIONS
  fMRI connectivity indices distinguish patients with MCI who undergo cognitive decline and conversion to AD from those who remain stable over a 2- to 3-year follow-up period. Our data support the notion of different functional brain connectivity endophenotypes for "early" vs "late" MCI, which are associated with different baseline memory scores and different rates of progression and conversion.
authors.affiliation: Department of Radiology and Brain Imaging and Analysis Center, Duke University Medical Center, Durham, NC, USA. jeffrey.petrella@duke.edu
authors.forename: J R
authors.initials: JR
authors.lastname: Petrella
authors.forename: F C
authors.initials: FC
authors.lastname: Sheldon
authors.forename: S E
authors.initials: SE
authors.lastname: Prince
authors.forename: V D
authors.initials: VD
authors.lastname: Calhoun
authors.forename: P M
authors.initials: PM
authors.lastname: Doraiswamy
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000473:pathology / Q000523:psychology; D003072:Cognition Disorders / Q000473:pathology* / Q000523:psychology*; D015331:Cohort Studies; D018450:Disease Progression; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008137:Longitudinal Studies; D008279:Magnetic Resonance Imaging / Q000379:methods; D008297:Male; D008875:Middle Aged; D009415:Nerve Net / Q000473:pathology*; D009483:Neuropsychological Tests