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From the Departments of Diagnostic Radiology and MR Research Laboratory (Drs. Jack and Gunter, Ms. Shiung), Neurology (Drs. Knopman, Boeve, and Petersen), Health Sciences Research (Dr. O’Brien, Mr. Weigand), Psychiatry and Psychology (Drs. Smith and Ivnik), and Internal Medicine (Dr. Tangalos), Mayo Clinic and Foundation, Rochester, MN.
Address correspondence and reprint requests to Dr. Clifford R. Jack, Jr., Mayo Clinic, Department of Radiology, 200 First Street SW, Rochester, MN 55905; e-mail: jack.clifford{at}mayo.edu
Objective: To test the hypothesis that the atrophy rate measured from serial MRI studies is associated with time to subsequent clinical conversion to a more impaired state in both cognitively healthy elderly subjects and in subjects with amnestic mild cognitive impairment (MCI).
Methods: Ninety-one healthy elderly patients and 72 patients with amnestic MCI who met inclusion criteria were identified from the Mayo Alzheimer’s Disease Research Center and Alzheimer’s Disease Patient Registry. Atrophy rates of four different brain structures—hippocampus, entorhinal cortex, whole brain, and ventricle—were measured from a pair of MRI studies separated by 1 to 2 years. The time of the second scan marked the beginning of the clinical observation period.
Results: During follow-up, 13 healthy patients converted to MCI or Alzheimer disease (AD), whereas 39 MCI subjects converted to AD. Among those healthy at baseline, only larger ventricular annual percent volume change (APC) was associated with a higher risk of conversion (hazard ratio for a 1-SD increase 1.9, p = 0.03). Among MCI subjects, both greater ventricular volume APC (hazard ratio for a 1-SD increase 1.7, p < 0.001) and greater whole brain APC (hazard ratio for a 1-SD increase 1.4, p = 0.007) increased the risk of conversion to AD. Both ventricular APC (hazard ratio for a 1-SD increase 1.59, p = 0.001) and whole brain APC (hazard ratio for a 1-SD increase 1.32, p = 0.009) provided additional predictive information to covariate-adjusted cross-sectional hippocampal volume at baseline about the risk of converting from MCI to AD.
Discussion: Higher whole brain and ventricle atrophy rates 1 to 2 years before baseline are associated with an increased hazard of conversion to a more impaired state. Combining a measure of hippocampal volume at baseline with a measure of either whole brain or ventricle atrophy rates from serial MRI scans provides complimentary predictive information about the hazard of subsequent conversion from mild cognitive impairment to Alzheimer disease. However, overlap among those who did vs those who did not convert indicate that these measures are unlikely to provide absolute prognostic information for individual patients.
Supported by the National Institute on Aging (AG16574, AG06786, and AG11378), and The Robert H. and Clarice Smith and Abigail Van Buren Alzheimer’s Disease Research Program.
Disclosure: The authors report no conflicts of interest.
Received November 3, 2004. Accepted in final form July 8, 2005.
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