[¹¹C]-MP4A PET Cholinergic Measurements in Amnestic Mild Cognitive Impairment, Probable Alzheimer's Disease, and Dementia with Lewy Bodies: A Bayesian Method and Voxel-Based Analysis

Article type: Research Article

Authors: Marcone, Alessandra^{a; 1} | Garibotto, Valentina^{b; c; d; 1} | Moresco, Rosa Maria^{c; d; i} | Florea, Ioanaⁱ | Panzacchi, Andrea^c | Carpinelli, Assunta^d | Virta, Jere R.^e | Tettamanti, Marco^{b; c} | Borroni, Barbara^f | Padovani, Alessandro^f | Bertoldo, Alessandra^g | Herholz, Karl^h | Rinne, Juha O.^e | Cappa, Stefano Francesco^{a; b} | Perani, Daniela^{a; b; c; d; *}

Affiliations: [a] Clinical Neurosciences Department, San Raffaele Turro Hospital, San Raffaele Scientific Institute, Milan, Italy | [b] Vita Salute San Raffaele University, Milan, Italy | [c] Nuclear Medicine Department, San Raffaele Scientific Institute Milan, Milan, Italy | [d] IBFM-CNR, Milan, Italy | [e] Turku PET Centre, University of Turku, Turku, Finland | [f] Centre for Ageing Brain and Neurodegenerative Disorders, Neurology Unit, University of Brescia, Brescia, Italy | [g] Department of Information Engineering, University of Padua, Padua, Italy | [h] Wolfson Molecular Imaging Centre, University of Manchester, Manchester, United Kingdom | [i] University of Milan-Bicocca, Milan, Italy

Correspondence: [*] Correspondence to: Daniela Perani, M.D., Vita Salute San Raffaele University, Nuclear Medicine Unit and Division of Neuroscience, San Raffaele Scientific Institute, via Olgettina 60 – Milan 20132, Italy. Tel.: +39 0226432224; Fax: +39 0226415202; E-mail: [email protected].

Note: [1] These authors contributed equally to this work.

Abstract: Non-invasive approaches for positron emission tomography (PET) parametric imaging of acetylcholinesterase (AChE) activity have been developed and applied to the investigation of dementia, mainly Alzheimer's disease (AD), but also dementia with Lewy bodies (DLB), not including, however, patients in the early disease stage. The few cholinergic PET studies on mild cognitive impairment (MCI) did not provide clinical follow-up. One limitation of the methods used so far is the relatively low sensitivity in measuring subcortical or deep cortical structures, which might represent specific disease markers. Here we assessed AChE activity with [11C]-MP4A and PET by a maximum a posteriori Bayesian method (MAPB) based on a 2-tissue compartment-3-rate-constant reference region model. 30 subjects were included: 10 multi-domain amnestic MCI (aMCI) with a follow up of 2 years, 7 probable AD (pAD), 4 DLB subjects, and 9 healthy controls. Regions of interest and voxel-based statistical parametric mapping analyses revealed significant and widespread AChE reductions in several cortical regions and in the hippocampus in all pAD subjects and aMCI subjects who progressed to AD (converters). Noteworthy, hippocampal AChE activity correlated significantly with long-term verbal and non-verbal memory in both aMCI converters and pAD. The pattern was more heterogeneous in early DLB patients, with only 2 out of 4 cases showing a severe or intermediate reduction of AChE activity. The comparable AChE reductions in pAD and aMCI converters indicate the presence of a widespread impairment of the cholinergic system already in the MCI phase. A more variable degree of cholinergic dysfunction is present in early DLB.

Keywords: ¹¹C MP4 PET, acetylcholinesterase activity, Alzheimer's disease, amnestic mild cognitive impairment, dementia with Lewy bodies

DOI: 10.3233/JAD-2012-111748

Journal: Journal of Alzheimer's Disease, vol. 31, no. 2, pp. 387-399, 2012