title: The Oregon brain aging study: neuropathology accompanying healthy aging in the oldest old.
abstract: OBJECTIVE
  To describe the relationship between neuropathologic aging and longitudinal measures of cognitive function in healthy oldest old individuals.
  
  
  METHODS
  Nondemented individuals without cardiovascular or other age-associated diseases of age > or =85 years were followed until death. Regional postmortem measures of senile plaque (SP) and neurofibrillary tangle (NFT) severity were examined in relationship to clinical status, cognitive measures, and rate of cognitive change.
  
  
  RESULTS
  Among 19 healthy individuals, 10 became demented or had incipient dementia develop. Clinical status and rate of change in cognitive scores correlated with increasing brain lesion burden, particularly in neocortical regions. Compared to demented individuals, nondemented individuals had few or no neocortical NFT (p = 0.009) or SP (p = 0.001). There was a strong correlation between rate of cognitive change on Mini-Mental State Examination (MMSE) and neocortical NFT (r = 0.859, p = 0.001). The few NFT and SP in nondemented patients had a predilection for limbic areas.
  
  
  CONCLUSIONS
  These results support a continuum in which AD is infrequent in the healthy, cognitively stable, oldest old. The minimal abnormalities in cognitively stable individuals are consistent with the notion that preclinical pathologic AD precedes obvious cognitive impairment. Longitudinal cognitive testing shows an increased burden of neuropathologic changes in those who have cognitive decline but are not functionally impaired and do not meet criteria for the diagnosis of dementia. The strong relationship between cumulative pathologic changes and rate of cognitive decline suggests that these lesions may have clinical consequences at any age and are not likely to be benign senescent changes.
authors.affiliation: Veterans Affairs Medical Center, Department of Neurology, Oregon Health Sciences University, Portland 97201-3098, USA. greens@ohsu.edu
authors.forename: M S
authors.initials: MS
authors.lastname: Green
authors.forename: J A
authors.initials: JA
authors.lastname: Kaye
authors.forename: M J
authors.initials: MJ
authors.lastname: Ball
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000375:Aging / Q000502:physiology* / Q000523:psychology; D001057:Apolipoproteins E / Q000235:genetics; D001921:Brain / Q000473:pathology*; D003071:Cognition; D003704:Dementia / Q000209:etiology / Q000473:pathology / Q000523:psychology; D005260:Female; D005838:Genotype; D006801:Humans; D008137:Longitudinal Studies; D008297:Male; D009460:Neurologic Examination; D009483:Neuropsychological Tests; D058225:Plaque, Amyloid / Q000473:pathology; D012016:Reference Values; D012307:Risk Factors
chemical_list: D001057:Apolipoproteins E