title: White matter lesions and the cholinergic deficit in aging and mild cognitive impairment.
abstract: In Alzheimer's disease (AD), white matter lesions (WMLs) are associated with an increased risk of progression from mild cognitive impairment (MCI) to dementia, while memory deficits have, at least in part, been linked to a cholinergic deficit. We investigated the relationship between WML load assessed with the Scheltens scale, cerebral acetylcholinesterase (AChE) activity measured with [11C]N-methyl-4-piperidyl acetate PET, and neuropsychological performance in 17 patients with MCI due to AD and 18 cognitively normal older participants. Only periventricular, not nonperiventricular, WML load negatively correlated with AChE activity in both groups. Memory performance depended on periventricular and total WML load across groups. Crucially, AChE activity predicted memory function better than WML load, gray matter atrophy, or age. The effects of WML load on memory were fully mediated by AChE activity. Data suggest that the contribution of WML to the dysfunction of the cholinergic system in MCI due to AD depends on WML distribution. Pharmacologic studies are warranted to explore whether this influences the response to cholinergic treatment.
authors.affiliation: Department of Neurology, University Hospital Cologne, Cologne, Germany; Cognitive Neuroscience, Institute of Neuroscience and Medicine (INM-3), Research Center Jülich, Jülich, Germany; Max Planck Institute for Metabolism Research, Cologne, Germany. Electronic address: nils.richter@uk-koeln.de.
authors.forename: Nils
authors.initials: N
authors.lastname: Richter
authors.affiliation: Department of Neurology, University Hospital Cologne, Cologne, Germany; Gériatrie, CHU de Rouen, Rouen University Hospital, Rouen, Cedex, France.
authors.forename: Anne
authors.initials: A
authors.lastname: Michel
authors.affiliation: Department of Neurology, University Hospital Cologne, Cologne, Germany; Cognitive Neuroscience, Institute of Neuroscience and Medicine (INM-3), Research Center Jülich, Jülich, Germany.
authors.forename: Oezguer A
authors.initials: OA
authors.lastname: Onur
authors.affiliation: Max Planck Institute for Metabolism Research, Cologne, Germany; Department of Nuclear Medicine, University Hospital Cologne, Cologne, Germany.
authors.forename: Lutz
authors.initials: L
authors.lastname: Kracht
authors.affiliation: Department of Nuclear Medicine, University Hospital Cologne, Cologne, Germany.
authors.forename: Markus
authors.initials: M
authors.lastname: Dietlein
authors.affiliation: Max Planck Institute for Metabolism Research, Cologne, Germany.
authors.forename: Marc
authors.initials: M
authors.lastname: Tittgemeyer
authors.affiliation: Nuclear Chemistry, Institute of Neuroscience and Medicine (INM-5), Research Center Jülich, Jülich, Germany; Institute for Radiochemistry and Experimental Molecular Imaging, University Hospital Cologne, Cologne, Germany.
authors.forename: Bernd
authors.initials: B
authors.lastname: Neumaier
authors.affiliation: Department of Neurology, University Hospital Cologne, Cologne, Germany; Cognitive Neuroscience, Institute of Neuroscience and Medicine (INM-3), Research Center Jülich, Jülich, Germany.
authors.forename: Gereon R
authors.initials: GR
authors.lastname: Fink
authors.affiliation: Department of Neurology, University Hospital Cologne, Cologne, Germany; Cognitive Neuroscience, Institute of Neuroscience and Medicine (INM-3), Research Center Jülich, Jülich, Germany.
authors.forename: Juraj
authors.initials: J
authors.lastname: Kukolja
mesh_terms: D000085:Acetates; D000110:Acetylcholinesterase / Q000378:metabolism*; D000368:Aged; D000369:Aged, 80 and over; D000375:Aging / Q000378:metabolism* / Q000523:psychology*; D000544:Alzheimer Disease / Q000150:complications; D060825:Cognitive Dysfunction / Q000000981:diagnostic imaging / Q000209:etiology* / Q000523:psychology; D005260:Female; D006801:Humans; D008297:Male; D008568:Memory / Q000502:physiology; D008875:Middle Aged; D009483:Neuropsychological Tests; D010880:Piperidines; D049268:Positron-Emission Tomography; D066127:White Matter / Q000000981:diagnostic imaging / Q000201:enzymology*
chemical_list: D000085:Acetates; C100518:N-methyl-4-piperidyl acetate; D010880:Piperidines; D000110:Acetylcholinesterase
keywords: Acetylcholinesterase; MP4A; PET