From the Division of Biology and Biomedical Sciences (A.F. Fotenos and Dr. Buckner), Washington
University Medical School, St. Louis MO, and Department of Psychology, Center for Brain Science, Howard
Hughes Medical Institute, Harvard University, Cambridge MA, Martinos Center, Massachusetts General
Hospital, Department of Radiology, Harvard Medical School, Boston, MA (Dr. Buckner). Supported by
grants AG 05681 and 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.
Address correspondence to Anthony Fotenos, Psychology Department Campus Box 1125, One Brookings
Drive, St. Louis, MO 63108; phone: (314) 566-0842; fax: (314) 935-4711; email: Anthony.Fotenos@wustl.edu.
Abstract: Structural MRI was used to estimate rates of gray matter, white
matter, and whole-brain volume decline in normal aging and Alzheimer’s Disease
(AD), based on a combination of cross-sectional and longitudinal sampling of 370
individuals age 18 to 97. Hierarchical regression of whole-brain volume estimates
normalized for head-size from nondemented individuals across the adult lifespan
revealed a strong linear, moderate quadratic pattern of decline beginning in early
adulthood, with later onset of white-matter than gray-matter loss. Whole-brain
volume differences were detected by age 30. Estimates of volume decline predicted
from the cross-sectional sample overlapped with the rates measured longitudinally
in older, nondemented individuals (mean decline of -0.45% per year). In serially
scanned individuals with very mild to mild dementia of the Alzheimer type,
atrophy rate more than doubled (-0.98% per year). These and related findings are
discussed in terms of a multiple factor framework of aging and AD.
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declined from 85% at age 20 to 74% at age 80, a mean rate of -0.23% per year
with acceleration into advanced aging. Hierarchical polynomial regression
showed that the relationship between nGM and age was predominantly
linear, with decline significant even in the young-adult range of 18 to 30. In
contrast, the relationship between nWM and age was quadratic, with
minimal decline in early adulthood. Considering only the nondemented
older adults, the cross-sectional volume loss ranged from -0.31% to -0.46%
per year, similar to the longitudinal estimate of -0.45% per year.
The longitudinal atrophy rate in the individuals with very mild to mild
DAT was -0.98% per year, approximately doubling the rate for the age-
matched, nondemented sample. Of the 43 nondemented (CDR 0)
individuals followed longitudinally from their first scan, six declined to a
CDR of 0.5 at the time of their last scan. The longitudinal atrophy rate of
those who started with a CDR of 0 and declined (-0.88%) matched the rate
of those who started with a CDR of 0.5 (-0.90% per year). Post hoc testing
revealed a trend toward a difference between the nondemented group
(CDR 0 to 0) and the decliner group (CDR 0 to 0.5), though the small sample
size limited statistical power.
Figure 1
Summary plot of cross-sectional and longitudinal whole-brain volume decline in
normal aging and AD. The “normal aging cross-sectional” curve represents the best-
fit polynomial regression of all nondemented individuals (n = 272, age 18 to 95). The
“normal aging longitudinal” line represents the mean slope and intercept of all
nondemented older adults scanned longitudinally (n = 38, age 65 to 95). The
“Alzheimer’s longitudinal” line represents the mean slope and intercept for all
longitudinally scanned individuals with AD (n = 33 CDR 0.5, age 65 to 93; n = 8
CDR 1, age 69 to 97). Note the overlap between cross-sectional and longitudinal
estimates of normal brain-volume decline, and the markedly accelerated atrophy
rate in AD.
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COMMENT
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