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From the Departments of Psychiatry (A.B.) and Neurology (B.C.D.), Massachusetts Alzheimer’s Disease Research Center and Athinoula A. Martinos Center for Biomedical Imaging, Massachusetts General Hospital and Harvard Medical School, Boston; Division of Cognitive and Behavioral Neurology (B.C.D.), Department of Neurology, Brigham & Women’s Hospital, Boston, MA; and Department of Neurology and Alzheimer’s Disease Research Center (J.C.M.), Washington University School of Medicine, St. Louis, MO.
Address correspondence and reprint requests to Dr. Brad Dickerson, MGH Gerontology Research Unit, 149 13th St., Suite 2691, Charlestown, MA 02129, bradd{at}nmr.mgh.harvard.edu
Objective: We previously used exploratory analyses across the entire cortex to determine that mild Alzheimer disease (AD) is reliably associated with a cortical signature of thinning in specific limbic and association regions. Here we investigated whether the cortical signature of AD-related thinning is present in individuals with questionable AD dementia (QAD) and whether a greater degree of regional cortical thinning predicts mild AD dementia.
Methods: Participants included 49 older adults with mild impairment consistent with mild cognitive impairment (Clinical Dementia Rating [CDR] = 0.5) at the time of structural MRI scanning. Cortical thickness was measured in nine regions of interest (ROIs) identified previously from a comparison of patients with mild AD and controls.
Results: Longitudinal clinical follow-up revealed that 20 participants converted to mild AD dementia (progressors) while 29 remained stable (nonprogressors) approximately 2.5 years after scanning. At baseline, QAD participants showed a milder degree of cortical thinning than typically seen in mild AD, and CDR Sum-of-Boxes correlated with thickness in temporal and parietal ROIs. Compared to nonprogressors, progressors showed temporal and parietal thinning. Using receiver operating characteristic curves, the thickness of an aggregate measure of these regions predicted progression to mild AD with 83% sensitivity and 65% specificity.
Conclusions: Thinning in specific cortical areas known to be affected by Alzheimer disease (AD) is detectable in individuals with questionable AD dementia (QAD) and predicts conversion to mild AD dementia. This method could be useful for identifying individuals at relatively high risk for imminent progression from QAD to mild AD dementia, which may be of value in clinical trials.
Abbreviations: AD = Alzheimer disease; ADT = AD signature thickness; AUC = area under the curve; CDR = Clinical Dementia Rating; CDR-SB = CDR Sum-of-Boxes; eTIV = estimated total intracranial volume; EV = entorhinal volume; HV = hippocampal volume; MCI = mild cognitive impairment; MCT = mean cortical thickness; MMSE = Mini-Mental State Examination; MTL = medial temporal lobe; MTLT = medial temporal lobe thickness; OC = older controls; QAD = questionable AD dementia; ROC = receiver operating characteristic; ROI = region of interest; WBV = whole brain volume.
Supplemental data at www.neurology.org
Editorial, page 1038
e-Pub ahead of print on December 24, 2008, at www.neurology.org.
Supported by grants from the NIA K23-AG22509, R01-AG29411, R21-AG29840, P50-AG05681, and P01-AG03991, NCRR P41-RR14075, U24-RR021382, the Alzheimer’s Association, Howard Hughes Medical Institute, and the Mental Illness and Neuroscience Discovery (MIND) Institute.
Disclosure: The authors report no disclosures.
Received June 18, 2008. Accepted in final form October 3, 2008.
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Neurology 2009 72: 1038-1039.
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