Normative estimates of cross-sectional and longitudinal brain volume decline in aging and AD

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.