Basal Forebrain and Hippocampus as Predictors of Conversion to Alzheimer’s Disease in Patients with Mild Cognitive Impairment – A Multicenter DTI and Volumetry Study

Article type: Research Article

Authors: Brueggen, Katharina^{a; *} | Dyrba, Martin^{a; b} | Barkhof, Frederik^c | Hausner, Lucrezia^d | Filippi, Massimo^e | Nestor, Peter J.^f | Hauenstein, Karlheinz^g | Klöppel, Stefan^h | Grothe, Michel J.^a | Kasper, Elisabethⁱ | Teipel, Stefan J.^{a; i} | and the EDSD study group

Affiliations: [a] DZNE, German Center for Neurodegenerative Diseases, Rostock, Germany | [b] MMIS group, University of Rostock, Rostock, Germany | [c] Department of Physics and Medical Technology, VU University Medical Center, Amsterdam, Netherlands | [d] Department of Geriatric Psychiatry, Zentralinstitut für Seelische Gesundheit Mannheim, University of Heidelberg, Mannheim, Germany | [e] Neuroimaging Research Unit, Institute of Experimental Neurology, Division of Neuroscience, Scientific Institute and University Vita-Salute San Raffaele, Milano, Italy | [f] DZNE, German Center for Neurodegenerative Diseases, Magdeburg, Germany | [g] Department of Radiology, University of Rostock, Rostock, Germany | [h] Department of Psychiatry and Psychotherapy, Freiburg Brain Imaging, University Clinic Freiburg, Freiburg, Germany | [i] Department of Psychosomatic Medicine, University Medicine Rostock, Rostock, Germany

Correspondence: [*] Correspondence to: Katharina Brueggen, DZNE German Center for Neurodegenerative Diseases, Rostock, c/o Zentrum für Nervenheilkunde, Gehlsheimer Straße 20, D-18147 Rostock. Tel.: +49 381 494 9478; Fax: +49 381 494 9472; [email protected]

Abstract: Background: Hippocampal grey matter (GM) atrophy predicts conversion from mild cognitive impairment (MCI) to Alzheimer’s disease (AD). Pilot data suggests that mean diffusivity (MD) in the hippocampus, as measured with diffusion tensor imaging (DTI), may be a more accurate predictor of conversion than hippocampus volume. In addition, previous studies suggest that volume of the cholinergic basal forebrain may reach a diagnostic accuracy superior to hippocampal volume in MCI. Objective: The present study investigated whether increased MD and decreased volume of the hippocampus, the basal forebrain and other AD-typical regions predicted time to conversion from MCI to AD dementia. Methods: 79 MCI patients with DTI and T1-weighted magnetic resonance imaging (MRI) were retrospectively included from the European DTI Study in Dementia (EDSD) dataset. Of these participants, 35 converted to AD dementia after 6–46 months (mean: 21 months). We used Cox regression to estimate the relative conversion risk predicted by MD values and GM volumes, controlling for age, gender, education and center. Results: Decreased GM volume in all investigated regions predicted an increased risk for conversion. Additionally, increased MD in the right basal forebrain predicted increased conversion risk. Reduced volume of the right hippocampus was the only significant predictor in a stepwise model combining all predictor variables. Conclusion: Volume reduction of the hippocampus, the basal forebrain and other AD-related regions was predictive of increased risk for conversion from MCI to AD. In this study, volume was superior to MD in predicting conversion.

Keywords: Diffusion tensor imaging, magnetic resonance imaging, Mild Cognitive Impairment, Alzheimer’s disease, atrophy, basal forebrain, cholinergic, early diagnosis

DOI: 10.3233/JAD-150063

Journal: Journal of Alzheimer's Disease, vol. 48, no. 1, pp. 197-204, 2015