title: [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.
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.
authors.affiliation: Clinical Neurosciences Department, San Raffaele Turro Hospital, San Raffaele Scientific Institute, Milan, Italy.
authors.forename: Alessandra
authors.initials: A
authors.lastname: Marcone
authors.forename: Valentina
authors.initials: V
authors.lastname: Garibotto
authors.forename: Rosa Maria
authors.initials: RM
authors.lastname: Moresco
authors.forename: Ioana
authors.initials: I
authors.lastname: Florea
authors.forename: Andrea
authors.initials: A
authors.lastname: Panzacchi
authors.forename: Assunta
authors.initials: A
authors.lastname: Carpinelli
authors.forename: Jere R
authors.initials: JR
authors.lastname: Virta
authors.forename: Marco
authors.initials: M
authors.lastname: Tettamanti
authors.forename: Barbara
authors.initials: B
authors.lastname: Borroni
authors.forename: Alessandro
authors.initials: A
authors.lastname: Padovani
authors.forename: Alessandra
authors.initials: A
authors.lastname: Bertoldo
authors.forename: Karl
authors.initials: K
authors.lastname: Herholz
authors.forename: Juha O
authors.initials: JO
authors.lastname: Rinne
authors.forename: Stefano Francesco
authors.initials: SF
authors.lastname: Cappa
authors.forename: Daniela
authors.initials: D
authors.lastname: Perani
mesh_terms: D000085:Acetates; D000110:Acetylcholinesterase / Q000378:metabolism; D000368:Aged; D000369:Aged, 80 and over; D000647:Amnesia / Q000000981:diagnostic imaging* / Q000378:metabolism / Q000523:psychology; D001499:Bayes Theorem; D002250:Carbon Radioisotopes; D060825:Cognitive Dysfunction / Q000000981:diagnostic imaging* / Q000378:metabolism / Q000523:psychology; D005260:Female; D006801:Humans; D020961:Lewy Body Disease / Q000000981:diagnostic imaging* / Q000378:metabolism / Q000523:psychology; D008297:Male; D008875:Middle Aged; D010880:Piperidines; D049268:Positron-Emission Tomography
chemical_list: D000085:Acetates; D002250:Carbon Radioisotopes; C100518:N-methyl-4-piperidyl acetate; D010880:Piperidines; D000110:Acetylcholinesterase