title: A Review of the Role of Anticholinergic Activity in Lewy Body Disease and Delirium.
abstract: We have previously proposed a hypothesis in which we argue that anticholinergic activity (AA) appears endogenously in Alzheimer's disease (AD). Acetylcholine (ACh) controls both cognitive function and inflammation. Consequently, when the downregulation of ACh reaches critical levels, the inflammatory system is upregulated and proinflammatory cytokines with AA appear. However, factors other than downregulation of ACh can produce AA; even if ACh downregulation does not reach critical levels, AA can still appear if one of these other AA-producing factors is added. These factors can include neurocognitive disorders other than AD, such as delirium and Lewy body disease (LBD). In delirium, ACh downregulation fails to reach critical levels, but AA appears due to the use of medicines, physical illnesses or mental stress (termed 'AA inserts'). In LBD, we speculate that AA appears endogenously, even in the absence of severe cognitive dysfunction, for 2 reasons. One reason is that patterns of ACh deterioration are different in LBD from those in AD, with synergistic actions between amyloid and α-synuclein thought to cause additional or severe symptoms that accelerate the disease course. The second reason is that AA occurs through disinhibition by reduced cortisol levels that result from severe autonomic parasympathetic dysfunction in LBD.
authors.affiliation: Department of Anesthesiology, School of Medicine, Juntendo University, Tokyo, Japan.
authors.forename: Yuka
authors.initials: Y
authors.lastname: Kitajima
authors.forename: Koji
authors.initials: K
authors.lastname: Hori
authors.forename: Kimiko
authors.initials: K
authors.lastname: Konishi
authors.forename: Masayuki
authors.initials: M
authors.lastname: Tani
authors.forename: Hiroi
authors.initials: H
authors.lastname: Tomioka
authors.forename: Norihisa
authors.initials: N
authors.lastname: Akashi
authors.forename: Misa
authors.initials: M
authors.lastname: Hosoi
authors.forename: Atsuko
authors.initials: A
authors.lastname: Inamoto
authors.forename: Sayaka
authors.initials: S
authors.lastname: Hasegawa
authors.forename: Nodoka
authors.initials: N
authors.lastname: Kikuchi
authors.forename: Akari
authors.initials: A
authors.lastname: Takahashi
authors.forename: Mitsugu
authors.initials: M
authors.lastname: Hachisu
mesh_terms: D000109:Acetylcholine / Q000378:metabolism; D000818:Animals; D018680:Cholinergic Antagonists / Q000378:metabolism* / Q000627:therapeutic use*; D003693:Delirium / Q000188:drug therapy* / Q000378:metabolism*; D006801:Humans; D020961:Lewy Body Disease / Q000188:drug therapy* / Q000378:metabolism*
chemical_list: D018680:Cholinergic Antagonists; D000109:Acetylcholine