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From the Division of Biology and Biomedical Sciences (A.F. Fotenos and Dr. Buckner), Mallinckrodt Institute of Radiology (Drs. Snyder and Buckner), Department of Neurology (Drs. Snyder and Morris), Howard Hughes Medical Institute (L.E. Girton and Dr. Buckner), and Department of Psychology (Dr. Buckner), Washington University, St. Louis, MO.
Address correspondence and reprint requests to Dr. Anthony Fotenos, HHMI at Washington University, Psychology Department Campus Box 1125, One Brookings Drive, St. Louis, MO 63108; e-mail: Anthony.Fotenos{at}wustl.edu
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.
Additional material related to this article can be found on the Neurology Web site. Go to www.neurology.org and scroll down the Table of Contents for the March 22 issue to find the title link for this article.
Supported by grants P50 AG 05681 and P01 AG 03991 from the National Institute on Aging, Bethesda, MD; IIRG-00-1944 from the Alzheimer's Association; the James S. McDonnell Foundation; and the Howard Hughes Medical Institute.
Received May 24, 2004. Accepted in final form November 30, 2004.
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