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NEUROLOGY 2009;73:457-465
© 2009 American Academy of Neurology

Regional rates of neocortical atrophy from normal aging to early Alzheimer disease

C. R. McDonald, PhD, L. K. McEvoy, PhD, L. Gharapetian, BS, C. Fennema-Notestine, PhD, D. J. Hagler, Jr, PhD, D. Holland, PhD, A. Koyama, BS, J. B. Brewer, MD, PhD, A. M. Dale, PhD For the Alzheimer’s Disease Neuroimaging Initiative

From the Department of Psychiatry (C.R.M., C.F.-N.), Multimodal Imaging Laboratory (C.R.M., L.K.M., L.G., C.F.-N., D.J.H., D.H., A.K., J.B.B., A.M.D.), Department of Radiology (L.K.M., D.J.H., D.H., J.B.B., A.M.D.), and Department of Neurosciences (J.B.B., A.M.D.), University of California, San Diego, CA.

Address correspondence and reprint requests to Dr. Carrie R. McDonald, Multimodal Imaging Laboratory, Suite C101, 8950 Villa La Jolla Dr., La Jolla, CA 92037 camcdonald{at}ucsd.edu

Objective: To evaluate the spatial pattern and regional rates of neocortical atrophy from normal aging to early Alzheimer disease (AD).

Methods: Longitudinal MRI data were analyzed using high-throughput image analysis procedures for 472 individuals diagnosed as normal, mild cognitive impairment (MCI), or AD. Participants were divided into 4 groups based on Clinical Dementia Rating Sum of Boxes score (CDR-SB). Annual atrophy rates were derived by calculating percent cortical volume loss between baseline and 12-month scans. Repeated-measures analyses of covariance were used to evaluate group differences in atrophy rates across regions as a function of impairment. Planned comparisons were used to evaluate the change in atrophy rates across levels of disease severity.

Results: In patients with MCI–CDR-SB 0.5–1, annual atrophy rates were greatest in medial temporal, middle and inferior lateral temporal, inferior parietal, and posterior cingulate. With increased impairment (MCI–CDR-SB 1.5–2.5), atrophy spread to parietal, frontal, and lateral occipital cortex, followed by anterior cingulate cortex. Analysis of regional trajectories revealed increasing rates of atrophy across all neocortical regions with clinical impairment. However, increases in atrophy rates were greater in early disease within medial temporal cortex, whereas increases in atrophy rates were greater at later stages in prefrontal, parietal, posterior temporal, parietal, and cingulate cortex.

Conclusions: Atrophy is not uniform across regions, nor does it follow a linear trajectory. Knowledge of the spatial pattern and rate of decline across the spectrum from normal aging to Alzheimer disease can provide valuable information for detecting early disease and monitoring treatment effects at different stages of disease progression.

Abbreviations: AD = Alzheimer disease; ADNI = Alzheimer’s Disease Neuroimaging Initiative; ANCOVA = analysis of covariance; CDR = Clinical Dementia Rating; CDR-SB = Clinical Dementia Rating Sum of Boxes score; MCI = mild cognitive impairment; MMSE = Mini-Mental State Examination; PI = Principal Investigator; RM = repeated-measures; ROI = region of interest; TIV = total intracranial volume; UCSD = University of California, San Diego.

Supplemental data at www.neurology.org

Supported by a grant (U24 RR021382) to the Morphometry Biomedical Informatics Research Network (http://www.nbirn.net) that is funded by the National Center for Research Resources at the National Institutes of Health, USA. Data collection and sharing for this project was funded by the Alzheimer’s Disease Neuroimaging Initiative (ADNI; Principal Investigator: Michael Weiner; NIH grant U01 AG024904). ADNI is funded by the National Institute on Aging, by the National Institute of Biomedical Imaging and Bioengineering, and through generous contributions from the following: Pfizer Inc., Wyeth Research, Bristol-Myers Squibb, Eli Lilly and Company, GlaxoSmithKline, Merck & Co. Inc., AstraZeneca AB, Novartis Pharmaceuticals Corporation, Alzheimer’s Association, Eisai Global Clinical Development, Elan Corporation plc, Forest Laboratories, and the Institute for the Study of Aging, with participation from the US Food and Drug Administration. Industry partnerships are coordinated through the Foundation for the National Institutes of Health. The grantee organization is the Northern California Institute for Research and Education, and the study is coordinated by the Alzheimer’s Disease Cooperative Study at the University of California, San Diego. ADNI data are disseminated by the Laboratory of Neuro Imaging at the University of California, Los Angeles.

Disclosure: Author disclosures are provided at the end of the article.

Received February 6, 2009. Accepted in final form May 1, 2009.






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