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NEUROLOGY 2009;72:1519-1525
© 2009 American Academy of Neurology

Risk of dementia in MCI

Combined effect of cerebrovascular disease, volumetric MRI, and 1H MRS

K. Kantarci, MD, S. D. Weigand, MS, S. A. Przybelski, BS, M. M. Shiung, BA, J. L. Whitwell, PhD, S. Negash, PhD, D. S. Knopman, MD, B. F. Boeve, MD, P. C. O’Brien, PhD, R. C. Petersen, MD, PhD and C. R. Jack, Jr, MD

From the Department of Diagnostic Radiology (K.K., M.M.S., J.L.W., C.R.J.), Division of Biostatistics (S.D.W., S.A.P., P.C.O.), Departments of Psychiatry and Psychology (S.N.), and Department of Neurology (D.S.K., B.F.B., R.C.P.), Mayo Clinic, Rochester, MN.

Address correspondence and reprint requests to Dr. Kejal Kantarci, Mayo Clinic, 200 First St. SW, Rochester, MN 55905 kantarci.kejal{at}mayo.edu

Objective: To investigate the combined ability of hippocampal volumes, 1H magnetic resonance spectroscopy (MRS) metabolites, and cerebrovascular disease to predict the risk of progression to dementia in mild cognitive impairment (MCI).

Methods: We identified 151 consecutively recruited subjects with MCI from the Mayo Clinic Alzheimer’s Disease Research Center and Patient Registry who underwent MRI and 1H MRS studies at baseline and were followed up with approximately annual clinical examinations. A multivariable proportional hazards model that considered all imaging predictors simultaneously was used to determine whether hippocampal volumes, posterior cingulate gyrus 1H MRS metabolites, white matter hyperintensity load, and presence of cortical and subcortical infarctions are complementary in predicting the risk of progression from MCI to dementia.

Results: Seventy-five subjects with MCI progressed to dementia by last follow-up. The model that best predicted progression to dementia included age, sex, hippocampal volumes, N-acetylaspartate (NAA)/creatine (Cr) on 1H MRS, and cortical infarctions. Based on age- and sex-adjusted Kaplan–Meier plots, we estimated that by 3 years, 26% of the MCI patients with normal hippocampal volumes, NAA/Cr ratios >1 SD, and no cortical infarctions will progress to dementia, compared with 78% of the MCI patients with hippocampal atrophy, low NAA/Cr (≤1 SD), and cortical infarction.

Conclusions: Multiple magnetic resonance (MR) markers of underlying dementia pathologies improve the ability to identify patients with prodromal dementia over a single MR marker, supporting the concept that individuals with multiple brain pathologies have increased odds of dementia compared with individuals with a single pathology.

Abbreviations: AD = Alzheimer disease; ADPR = Alzheimer’s Disease Patient Registry; ADRC = Alzheimer’s Disease Research Center; AIC = Akaike Information Criteria; aMCI = amnestic mild cognitive impairment; CDR = Clinical Dementia Rating; Cho = choline; CI = confidence interval; Cr = creatine; DLB = dementia with Lewy bodies; DSM = Diagnostic and Statistical Manual of Mental Disorders; FLAIR = fluid-attenuated inversion recovery; FTLD = frontotemporal lobar degeneration; HR = hazard ratio; MCI = mild cognitive impairment; mI = myoinositol; MMSE = Mini-Mental State Examination; MR = magnetic resonance; MRS = magnetic resonance spectroscopy; NAA = N-acetylaspartate; naMCI = nonamnestic mild cognitive impairment; NIA = National Institute on Aging; WMH = white matter hyperintensity.

Supplemental data at www.neurology.org

Supported by the Paul B. Beeson Career Development Award in Aging K23 AG030935 (NIH/National Institute on Aging [NIA]), Alzheimer’s Association New Investigator Research Grant 03-4842, and the NIH Roadmap Multidisciplinary Clinical Research Career Development Award KL2 RR024151 (NIH/NCRR) to K.K.; P50 AG16574 (NIH/NIA) and U01 AG06786 (NIH/NIA) to R.C.P.; R01 AG11378 (NIH/NIA); the Alexander Family Professorship in Alzheimer’s Research to C.R.J.; and the Robert H. and Clarice Smith and Abigail Van Buren Alzheimer’s Disease Research Program.

Disclosure: The authors report no disclosures.

Received September 15, 2008. Accepted in final form February 3, 2009.






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