title: Normative estimates of cross-sectional and longitudinal brain volume decline in aging and AD.
abstract: OBJECTIVE
  To test the hypotheses 1) that whole-brain volume decline begins in early adulthood, 2) that cross-sectional and longitudinal atrophy estimates agree in older, nondemented individuals, and 3) that longitudinal atrophy accelerates in the earliest stages of Alzheimer disease (AD).
  
  
  METHODS
  High-resolution, high-contrast structural MRIs were obtained from 370 adults (age 18 to 97). Participants over 65 (n = 192) were characterized using the Clinical Dementia Rating (CDR) as either nondemented (CDR 0, n = 94) or with very mild to mild dementia of the Alzheimer type (DAT, CDR 0.5 and 1, n = 98). Of these older participants, 79 belonged to a longitudinal cohort and were imaged again a mean 1.8 years after baseline. Estimates of gray matter (nGM), white matter (nWM), and whole-brain volume (nWBV) normalized for head sizes were generated based on atlas registration and image segmentation.
  
  
  RESULTS
  Hierarchical regression of nWBV estimates from nondemented individuals across the adult lifespan revealed a strong linear, moderate quadratic pattern of decline beginning in early adulthood, with later onset of nWM than nGM loss. Whole-brain volume differences were detected by age 30. The cross-sectional atrophy model overlapped with the rates measured longitudinally in older, nondemented individuals (mean decline of -0.45% per year). In those individuals with very mild DAT, atrophy rate more than doubled (-0.98% per year).
  
  
  CONCLUSIONS
  Nondemented individuals exhibit a slow rate of whole-brain atrophy from early in adulthood with white-matter loss beginning in middle age; in older adults, the onset of dementia of the Alzheimer type is associated with a markedly accelerated atrophy rate.
authors.affiliation: Division of Biology and Biomedical Sciences, Psychology Department, HHMI, Washington University, St. Louis, MO 63108, USA. Anthony.Fotenos@wustl.edu
authors.forename: A F
authors.initials: AF
authors.lastname: Fotenos
authors.forename: A Z
authors.initials: AZ
authors.lastname: Snyder
authors.forename: L E
authors.initials: LE
authors.lastname: Girton
authors.forename: J C
authors.initials: JC
authors.lastname: Morris
authors.forename: R L
authors.initials: RL
authors.lastname: Buckner
mesh_terms: D000293:Adolescent; D000328:Adult; D000367:Age Factors; D000368:Aged; D000369:Aged, 80 and over; D000375:Aging / Q000473:pathology*; D000544:Alzheimer Disease / Q000175:diagnosis* / Q000503:physiopathology; D001284:Atrophy / Q000175:diagnosis* / Q000503:physiopathology; D001921:Brain / Q000473:pathology* / Q000503:physiopathology; D001931:Brain Mapping; D018450:Disease Progression; D005260:Female; D006801:Humans; D008137:Longitudinal Studies; D008279:Magnetic Resonance Imaging / Q000592:standards; D008297:Male; D008875:Middle Aged; D012016:Reference Values; D012044:Regression Analysis