Utility of Molecular and Structural Brain Imaging to Predict Progression from Mild Cognitive Impairment to Dementia

Article type: Research Article

Authors: Lan, Martin J.^{a; d; *} | Ogden, R. Todd^{a; d} | Kumar, Dileep^{a; d} | Stern, Yaakov^{b; e} | Parsey, Ramin V.^{f; g} | Pelton, Gregory H.^{a; c; e} | Rubin-Falcone, Harry^{a; d} | Pradhaban, Gnanavalli^{a; c} | Zanderigo, Francesca^{a; d} | Miller, Jeffrey M.^{a; d} | Mann, J. John^{a; d} | Devanand, D.P.^{a; c}

Affiliations: [a] Department of Psychiatry, Columbia University College of Physicians and Surgeons, New York, NY, USA | [b] Department of Neurology, Columbia University College of Physicians and Surgeons, New York, NY, USA | [c] Division of Geriatric Psychiatry, New York State Psychiatric Institute, New York, NY, USA | [d] Division of Molecular Imaging and Neuropathology, New York State Psychiatric Institute, New York, NY, USA | [e] Taub Institute for Research on Alzheimer’s Disease and Aging Brain, New York, NY, USA | [f] Department of Psychiatry, Stony Brook University, Stony Brook, NY, USA | [g] Department of Radiology, Stony Brook University, Stony Brook, NY, USA

Correspondence: [*] Correspondence to: Martin J. Lan, MD, PhD, 1051 Riverside Drive, Unit 42, New York, NY 10032, USA. Tel.: +1 646 774 7610; Fax: +1 646 774 7560; E-mail: lanmart@nyspi.columbia.edu.

Abstract: This project compares three neuroimaging biomarkers to predict progression to dementia in subjects with mild cognitive impairment (MCI). Eighty-eight subjects with MCI and 40 healthy controls (HCs) were recruited. Subjects had a 3T magnetic resonance imaging (MRI) scan, and two positron emission tomography (PET) scans, one with Pittsburgh compound B ([11C]PIB) and one with fluorodeoxyglucose ([18F]FDG). MCI subjects were followed for up to 4 y and progression to dementia was assessed on an annual basis. MCI subjects had higher [11C]PIB binding potential (BPND) than HCs in multiple brain regions, and lower hippocampus volumes. [11C]PIB BPND, [18F]FDG standard uptake value ratio (SUVR), and hippocampus volume were associated with time to progression to dementia using a Cox proportional hazards model. [18F]FDG SUVR demonstrated the most statistically significant association with progression, followed by [11C]PIB BPND and then hippocampus volume. [11C]PIB BPND and [18F]FDG SUVR were independently predictive, suggesting that combining these measures is useful to increase accuracy in the prediction of progression to dementia. Hippocampus volume also had independent predictive properties to [11C]PIB BPND, but did not add predictive power when combined with the [18F]FDG SUVR data. This work suggests that PET imaging with both [11C]PIB and [18F]FDG may help to determine which MCI subjects are likely to progress to AD, possibly directing future treatment options.

Keywords: Alzheimer’s disease, mild cognitive impairment, prognosis, PET, volumetric MRI

DOI: 10.3233/JAD-161284

Journal: Journal of Alzheimer's Disease, vol. 60, no. 3, pp. 939-947, 2017