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Longitudinal pattern of regional brain volume change differentiates normal aging from MCI

From the Laboratory of Personality and Cognition (I.D., Y.A., S.M.R.), National Institute on Aging, Baltimore, MD; Department of Radiology (C.D., X.W., D.S.), University of Pennsylvania, Philadelphia; and Department of Radiology (M.K.), Johns Hopkins Medical Institutions, Baltimore.

Address correspondence and reprint requests to Dr. Susan Resnick, LPC/GRC/NIA, 5600 Nathan Shock Dr., Baltimore, MD 21224 resnicks{at}mail.nih.gov.

Background: Neuroimaging measures have potential as surrogate markers of disease through identification of consistent features that occur prior to clinical symptoms. Despite numerous investigations, especially in relation to the transition to clinical impairment, the regional pattern of brain changes in clinically normal older adults has not been established. We predict that the regions that show early pathologic changes in association with Alzheimer disease will show accelerated volume loss in mild cognitive impairment (MCI) compared to normal aging.

Methods: Through the Baltimore Longitudinal Study of Aging, we prospectively evaluated 138 nondemented individuals (age 64–86 years) annually for up to 10 consecutive years. Eighteen participants were diagnosed with MCI over the course of the study. Mixed-effects regression was used to compare regional brain volume trajectories of clinically normal individuals to those with MCI based on a total of 1,017 observations.

Results: All investigated volumes declined with normal aging (p < 0.05). Accelerated change with age was observed for ventricular CSF (vCSF), frontal gray matter, superior, middle, and medial frontal, and superior parietal regions (p 0.04). The MCI group showed accelerated changes compared to normal controls in whole brain volume, vCSF, temporal gray matter, and orbitofrontal and temporal association cortices, including the hippocampus (p 0.04).

Conclusion: Although age-related regional volume loss is apparent and widespread in nondemented individuals, mild cognitive impairment is associated with a unique pattern of structural vulnerability reflected in differential volume loss in specific regions. Early identification of patterns of abnormality is of fundamental importance for detecting disease onset and tracking progression.

Abbreviations: AD = Alzheimer disease; BIMC = Blessed Information Memory Concentration Scale; BLSA = Baltimore Longitudinal Study of Aging; GM = gray matter; ICV = intracranial volume; MCI = mild cognitive impairment; MMSE = Mini-Mental State Examination; vCSF = ventricular CSF; WM = white matter.

Supported in part by NIH funding sources N01-AG-3-2124 and R01-AG14971 and by the Intramural Research Program of the NIH, National Institute on Aging.

Disclosure: The authors report no disclosures.

Medical Device: GE Signa 1.5T scanner (GE, Milwaukee, WI).

Received October 29, 2008. Accepted in final form March 2, 2009.