Serum Anticholinergic Activity: A Possible Peripheral Marker of the Anticholinergic Burden in the Central Nervous System in Alzheimer’s Disease

Hori, Koji; Konishi, Kimiko; Tani, Masayuki; Tomioka, Haruaki; Akita, Ryo; Kitajima, Yuriko; Aoki, Mari; Yokoyama, Sachiko; Azuma, Kazunari; Ikuse, Daisuke; Akashi, Norihisa; Hosoi, Misa; Jinbo, Koichi; Hachisu, Mitsugu

doi:10.1155/2014/459013

Cited by 27 publications

(63 citation statements)

References 45 publications

(66 reference statements)

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“…Moreover, we also speculate this hyperactivity of inflammatory system also induces anticholinergic activity (AA) and this AA accelerates amyloid pathology [5]. Based on this speculation, we propose "the hypothesis of endogenous appearance of AA in AD" [6].…”

Section: Opinionmentioning

confidence: 86%

“…Based on this speculation, we propose "the hypothesis of endogenous appearance of AA in AD" [6]. That is, when the downregulation of ACh reaches critical level, AA appears endogenously by way of hyperactivation of inflammatory system and accelerates amyloid pathology [5,6]. Because the factors those cause AA and now reported three other than downregulation of ACh, i.e., medication [7], physical illness [8] and mental stress [9].…”

Section: Opinionmentioning

confidence: 99%

“…However, ACh also suppresses inflammatory system [2], therefore, downregulation of ACh not only causes cognitive dysfunction, but also accelerates inflammatory system. This hyperactivity of inflammatory system is related with various neuropsychiatric disorders including Alzheimer's disease (AD) [3] and depression [4].Moreover, we also speculate this hyperactivity of inflammatory system also induces anticholinergic activity (AA) and this AA accelerates amyloid pathology [5]. Based on this speculation, we propose "the hypothesis of endogenous appearance of AA in AD" [6].…”

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confidence: 94%

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Role of Cholinergic System in Neuropsychiatric Disorders

Hori¹

2017

Anat Physiol

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OpinionNeedless to say acetylcholine (ACh) is relared with cognitive function [1]. However, ACh also suppresses inflammatory system [2], therefore, downregulation of ACh not only causes cognitive dysfunction, but also accelerates inflammatory system. This hyperactivity of inflammatory system is related with various neuropsychiatric disorders including Alzheimer's disease (AD) [3] and depression [4].Moreover, we also speculate this hyperactivity of inflammatory system also induces anticholinergic activity (AA) and this AA accelerates amyloid pathology [5]. Based on this speculation, we propose "the hypothesis of endogenous appearance of AA in AD" [6]. That is, when the downregulation of ACh reaches critical level, AA appears endogenously by way of hyperactivation of inflammatory system and accelerates amyloid pathology [5,6]. Because the factors those cause AA and now reported three other than downregulation of ACh, i.e., medication [7], physical illness [8] and mental stress [9]. Therefore, it is natural that when based on the small amount of deterioration of ACh other AA insert is added, AA also appears [10]. In fact, we showed the patient with AD at MCI level whose serum anticholinergic activity might be positive caused by both small amount of down regulation of ACh and mental stress [11]. Moreover, overburden of cholinergic system might also attribute to the appearance of AA because ACh is no more upregulated in order to compensate for AA insert (upregulation of ACh). Therefore there might be a possibility of the appearance of AA in other disease than AD. We also speculate there might be a possibility of the endogenous appearance of AA in depression and Lewy body disease (LBD). Increased activity of the hypothalamic-pituitary-adrenal (HPA) axis and the small amount of downregulation of ACh. It is plausible to conclude that in depression and LBD AA might appear endogenously [12,13]. In depression, the cholinergic system is burdened secondarily to the underlying depressive pathology. During remission, activity of cholinacetyl transferase (ChAT), an enzyme that produces ACh, might be sufficiently upregulated to compensate for the cholinergic burden caused by depressive pathology. However, at the pathological state (depressive state), more upregulation of ACh is not impossible because the ChAT activity is already upregulate. Therefore, in depression there might be a possibility of endogenous appearance of AA [14]. In delirium, we also speculate there might be a possibility of the appearance of AA in delirium. In delirium, increased activity of the HPA axis by exogenous factor, i.e., physical illness, medication or mental stress and the small amount of downregulation of ACh caused by aging or AD, AA also appears.From these considerations we speculate that at least in AD, LBD and depression, the progression of disease might be related with AA at least late sage. Alternatively at late phase of AD, LBD and depression, main pathology might be amyloid pathology. We propose the concept of "anticholinergic spectrum disor...

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Section: Opinionmentioning

confidence: 86%

Section: Opinionmentioning

confidence: 99%

mentioning

confidence: 94%

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Role of Cholinergic System in Neuropsychiatric Disorders

Hori¹

2017

Anat Physiol

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“…However, it is considered that ACh also regulates inflammatory system, i. e., referred to as antiinflammatory pathway [8,9]. Therefore, we speculated that some cytokines caused by upregulations of inflammations have anticholinergic activity (AA), which accelerated AD pathology (amyloids and tau) [10][11][12]. Generally speaking, AD progresses more rapidly in moderate stage than in mild stage [13].…”

Section: Discussionmentioning

confidence: 99%

Rivastigimine for Relatively Younger Alzheimer’s Disease Patient

Horiuchi¹,

Hori

Hosoi³

et al. 2014

rain Disord Ther

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We presented the patient with relative younger Alzheimer's disease (AD) whose clinical symptoms and cognitive functions were responsive not to donepezil but to rivastigmine. Age of initial visit our memory clinic of this patient was relatively younger. It is considered that in relative older patient both AD pathology and aging cause cognitive dysfunctions. However, in relative younger patient not aging but only AD pathology causes cognitive dysfunctions. Therefore, AD pathology was thought to be more pronounced in our patient than relatively older patients with same cognitive disturbances. In AD, glia cells and amyloids proliferate and nervous cells shrink. Butyrylcholinesterase (BuChE) exists in glia cells and amyloids. Therefore, when AD progresses, acetylcholinesterase (AChE) decreases and BuChE increases. Accordingly the ratio of BuChE/AChE increases. Therefore, when at mild stage such our patient, not donepezil but rivastigmine which has inhibiting actions on both AChE and BuChE was suitable.

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“…The refined hypothesis was derived from the findings presented in our 3 previous reports [1,2,3] and the review process we undertook. Therefore, it is a limitation of this special issue that our discussion is derived mainly from reviewing our 2 original articles [4,5], 3 case reports [6,7,8] and review articles [1,2,3] whose findings have not been proven in large-scale studies. We have presented our refined hypothesis in just 1 article [9], and this special issue marks the first publication of our additional suggestions, implications and case presentations supporting our revised hypothesis.…”

Section: Figmentioning

confidence: 99%