title: Hypothesis of Endogenous Anticholinergic Activity in Alzheimer's Disease.
abstract: In this article, we review and repropose our hypothesis of the endogenous appearance of anticholinergic activity (AA) in Alzheimer's disease (AD). First, we introduce our previous articles and speculate that, because acetylcholine (ACh) regulates both cognitive function and inflammation, downregulation of this neurotransmitter causes upregulation of the inflammatory system. AA then appears endogenously with the production of cytokines and the downregulation of ACh in AD. To support our hypothesis, we present a female AD patient whose AA was considered to occur endogenously through her AD pathology. Her serum anticholinergic activity (SAA) was positive at her first visit to our memory clinic, was negative at the 1-year and 2-year follow-up visits, and had become positive again by 3 years. We speculate that the initial positive SAA was related to her AD pathology plus mental stress, and that her SAA at 3 years was related to her AD pathology only. Consequently, we believe that 2 patterns of SAA positivity (and therefore AA) exist. One occurs when the downregulation of ACh reaches a critical level, and the other occurs with the addition of some other factor such as medication, induced illness or mental stress that causes AA to affect AD pathology. Finally, we consider the pharmacotherapy of AD based on the proposed hypothesis and conclude that cholinesterase inhibitors can be used to prevent rapid disease progression, whereas N-methyl-D-aspartate receptor antagonists should be reserved for the treatment of AD that is already in a stage of rapid progression. We also propose a staging schema for patients with AD.
authors.affiliation: Department of Psychiatry, Showa University Northern Yokohama Hospital, Yokohama, Japan.
authors.forename: Kimiko
authors.initials: K
authors.lastname: Konishi
authors.forename: Koji
authors.initials: K
authors.lastname: Hori
authors.forename: Masayuki
authors.initials: M
authors.lastname: Tani
authors.forename: Hiroi
authors.initials: H
authors.lastname: Tomioka
authors.forename: Yuka
authors.initials: Y
authors.lastname: Kitajima
authors.forename: Norihisa
authors.initials: N
authors.lastname: Akashi
authors.forename: Atsuko
authors.initials: A
authors.lastname: Inamoto
authors.forename: Kenzo
authors.initials: K
authors.lastname: Kurosawa
authors.forename: Haijime
authors.initials: H
authors.lastname: Yuda
authors.forename: Takahiro
authors.initials: T
authors.lastname: Hanashi
authors.forename: Hiromi
authors.initials: H
authors.lastname: Ouchi
authors.forename: Misa
authors.initials: M
authors.lastname: Hosoi
authors.forename: Mitsugu
authors.initials: M
authors.lastname: Hachisu
mesh_terms: D000368:Aged; D000544:Alzheimer Disease / Q000188:drug therapy / Q000378:metabolism*; D014150:Antipsychotic Agents / Q000378:metabolism / Q000627:therapeutic use*; D018680:Cholinergic Antagonists / Q000378:metabolism / Q000627:therapeutic use*; D002800:Cholinesterase Inhibitors / Q000627:therapeutic use; D000077265:Donepezil; D005260:Female; D006801:Humans; D007189:Indans / Q000627:therapeutic use; D008297:Male; D008559:Memantine / Q000627:therapeutic use; D010880:Piperidines / Q000627:therapeutic use
chemical_list: D014150:Antipsychotic Agents; D018680:Cholinergic Antagonists; D002800:Cholinesterase Inhibitors; D007189:Indans; D010880:Piperidines; D000077265:Donepezil; D008559:Memantine