title: Functional, global and cognitive decline correlates to accumulation of Alzheimer's pathology in MCI and AD.
abstract: BACKGROUND
  Cognitive, global and functional instruments have been extensively investigated for correlations with neuropathological changes such as neurofibrillary tangles (NFTs), plaques, and synapse loss in the brain.
  
  
  OBJECTIVE
  Our objective is to correlate the functional, global and cognitive decline assessed clinically with the neuropathological changes observed in a large prospectively characterized cohort of mild cognitive impairment (MCI) and Alzheimer's disease (AD).
  
  
  METHODS
  We examined 150 subjects (16 MCI and 134 AD) that were prospectively assessed and longitudinally followed to autopsy. MCI subjects clinically met Petersen criteria for single or multi-domain amnestic MCI. AD subjects clinically met NINCDS-ADRDA criteria for probable or possible AD. All subjects received the Functional Assessment Staging (FAST), the Global Deterioration Scale (GDS), and the Mini Mental State Examination (MMSE) ante-mortem. Plaque and tangle counts were gathered for hippocampus, entorhinal cortex, frontal, temporal and parietal cortices. Braak staging was performed as well.
  
  
  RESULTS
  The GDS, FAST and MMSE correlated with plaque counts in all regions. The GDS, FAST and MMSE correlated with tangle counts in in all regions. The three instruments also correlated with the Braak score. The MMSE and GDS correlate better than the FAST in most regions.
  
  
  CONCLUSIONS
  Accumulation of neuropathology appears to correlate with functional, global, and cognitive decline as people progress from MCI through AD.
authors.affiliation: The Cleo Roberts Center, Banner-Sun Health Research Institute, 10515 W. Santa Fe Dr Sun City, AZ 85351, USA. Marwan.sabbagh@bannerhealth.com
authors.forename: M N
authors.initials: MN
authors.lastname: Sabbagh
authors.forename: K
authors.initials: K
authors.lastname: Cooper
authors.forename: J
authors.initials: J
authors.lastname: DeLange
authors.forename: J D
authors.initials: JD
authors.lastname: Stoehr
authors.forename: K
authors.initials: K
authors.lastname: Thind
authors.forename: T
authors.initials: T
authors.lastname: Lahti
authors.forename: B
authors.initials: B
authors.lastname: Reisberg
authors.forename: L
authors.initials: L
authors.lastname: Sue
authors.forename: L
authors.initials: L
authors.lastname: Vedders
authors.forename: S R
authors.initials: SR
authors.lastname: Fleming
authors.forename: T G
authors.initials: TG
authors.lastname: Beach
mesh_terms: D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000473:pathology* / Q000503:physiopathology / Q000523:psychology; D002540:Cerebral Cortex / Q000473:pathology / Q000503:physiopathology; D003072:Cognition Disorders / Q000473:pathology* / Q000503:physiopathology / Q000523:psychology; D015331:Cohort Studies; D004185:Disability Evaluation; D018450:Disease Progression; D018728:Entorhinal Cortex / Q000473:pathology / Q000503:physiopathology; D005260:Female; D006624:Hippocampus / Q000473:pathology / Q000503:physiopathology; D006801:Humans; D008137:Longitudinal Studies; D008297:Male; D016874:Neurofibrillary Tangles / Q000473:pathology; D009483:Neuropsychological Tests / Q000706:statistics & numerical data; D058225:Plaque, Amyloid / Q000473:pathology; D011237:Predictive Value of Tests; D011379:Prognosis; D011446:Prospective Studies; D012720:Severity of Illness Index