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

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

doi:10.1155/2014/459013

Abstract

We review the utility of serum anticholinergic activity (SAA) as a peripheral marker of anticholinergic activity (AA) in the central nervous system (CAA). We hypothesize that the compensatory mechanisms of the cholinergic system do not contribute to SAA if their system is intact and that if central cholinergic system deteriorates alone in conditions such as Alzheimer's disease or Lewy body dementia, CAA and SAA are caused by way of hyperactivity of inflammatory system and SAA is a marker of the anticholinergic burden in CNS. Taking into account the diurnal variations in the plasma levels of corticosteroids, which are thought to affect SAA, it should be measured at noon or just afterward.

Highlights

Anticholinergic activity (AA) has various adverse effects on both the central nervous system (CNS) and other parts of the body [1]
We reported the case of a 74-year-old woman who presented with amnesia and positive serum AA (SAA) at the stage of mild cognitive impairment, which disappeared after treatment with the cholinesterase inhibitor donepezil for 1 year [37]
Because the patient’s other medications and physical condition remained unchanged during the 1year period, we assumed that the appearance of SAA was because of proinflammatory changes caused by both ACh deficiency and psychological stress [37]; in other words, the concurrence of Alzheimer’s disease (AD) and psychological stress caused substantial inflammatory activities, which produced AA

Summary

Introduction

Anticholinergic activity (AA) has various adverse effects on both the central nervous system (CNS) and other parts of the body (peripheral tissues) [1]. The substances that appear in the serum or in the brain and that are related to positive SAA or CAA have not been identified yet [18]. 2. Utility and Limitations of SAA as a Peripheral Marker of the Anticholinergic Burden in CNS. SAA has been quantified by means of a radioreceptorbinding assay using muscarinic receptors in the forebrains excised from rats. The substances that appear in the serum or in the brain and are related to positive SAA or CAA are not known. It is worthwhile to identify these substances, and this task is especially relevant in patients with Alzheimer’s disease (AD), in whom the cerebral cholinergic system is thought to be involved in the pathogenesis. There are doubts about the association of SAA with AA in CNS

Endogenous Emergence of AA in AD

The Compensatory Mechanism of the Cholinergic System Does Not Give Rise to AA

When Should We Measure SAA?

Clinical Implications

Conclusions

Conflict of Interests