Subregional Basal Forebrain Atrophy in Alzheimer's Disease: A Multicenter Study

Article type: Research Article

Authors: Kilimann, Ingo^{a; b; *} | Grothe, Michel^a | Heinsen, Helmut^c | Alho, Eduardo Joaquim Lopez^c | Grinberg, Lea^{d; e} | Amaro Jr., Edson^f | dos Santos, Gláucia Aparecida Bento^f | da Silva, Rafael Emídio^f | Mitchell, Alex J.^g | Frisoni, Giovanni B.^h | Bokde, Arun L.W.ⁱ | Fellgiebel, Andreas^j | Filippi, Massimo^k | Hampel, Harald^l | Klöppel, Stefan^m | Teipel, Stefan J.^{a; b}

Affiliations: [a] German Center for Neurodegenerative Diseases (DZNE) Rostock/Greifswald, Rostock, Germany | [b] Department of Psychosomatic Medicine, Rostock University Medical Center, Rostock, Germany | [c] Laboratory of Morphological Brain Research, Department of Psychiatry, Psychosomatic Medicine and Psychotherapy, University of Würzburg, Würzburg, Germany | [d] Department of Neurology, University of California San Francisco, San Francisco, USA | [e] Aging Brain Study Group, LIM-22, Department of Pathology, University of Sao Paulo Medical School, Sao Paulo, Brazil | [f] Department of Radiology, University of Sao Paulo, Medical School, Sao Paulo, Brazil | [g] Department of Psycho-oncology, University of Leicester, Leicester, UK | [h] LENITEM Laboratory of Epidemiology, Neuroimaging and Telemedicine, IRCCS Centro San Giovanni di Dio, FBF, Brescia, Italy | [i] Cognitive Systems Group, Discipline of Psychiatry, School of Medicine and Trinity College Institute of Neuroscience (TCIN), Trinity College Dublin, Dublin, Ireland | [j] Department of Psychiatry, University Medical Center of Mainz, Mainz, Germany | [k] Neuroimaging Research Unit, Institute of Experimental Neurology, Division of Neuroscience, Scientific Institute and University “Vita-Salute” San Raffaele, Mailand, Italy | [l] Department of Psychiatry, Goethe University, Frankfurt, Germany | [m] Department of Psychiatry and Psychotherapy, Freiburg Brain Imaging, University Medical Center Freiburg, Freiburg, Germany

Correspondence: [*] Correspondence to: Ingo Kilimann, MD, DZNE, German Center for Neurodegenerative Diseases, Gehlsheimer Str. 20, 18147 Rostock, Germany. Tel.: +49 381 494 9526; Fax: +49 381 494 9472; E-mail: [email protected].

Abstract: Histopathological studies in Alzheimer's disease (AD) suggest severe and region-specific neurodegeneration of the basal forebrain cholinergic system (BFCS). Here, we studied the between-center reliability and diagnostic accuracy of MRI-based BFCS volumetry in a large multicenter data set, including participants with prodromal (n = 41) or clinically manifest AD (n = 134) and 148 cognitively healthy controls. Atrophy was determined using voxel-based and region-of-interest based analyses of high-dimensionally normalized MRI scans using a newly created map of the BFCS based on postmortem in cranio MRI and histology. The AD group showed significant volume reductions of all subregions of the BFCS, which were most pronounced in the posterior nucleus basalis Meynert (NbM). The mild cognitive impairment-AD group showed pronounced volume reductions in the posterior NbM, but preserved volumes of anterior-medial regions. Diagnostic accuracy of posterior NbM volume was superior to hippocampus volume in both groups, despite higher multicenter variability of the BFCS measurements. The data of our study suggest that BFCS morphometry may provide an emerging biomarker in AD.

Keywords: Atrophy, biomarker, cholinergic system, dementia, European DTI Study on Dementia

DOI: 10.3233/JAD-132345

Journal: Journal of Alzheimer's Disease, vol. 40, no. 3, pp. 687-700, 2014