Pharmacotherapy for Neurocognitive Disorders Based on the Hypothesis of Endogenous Appearance of Anticholinergic Activity

Abstract

We previously proposed the hypothesis of endogenous anticholinergic activity (AA) in Alzheimer's disease (AD). According to this hypothesis, the downregulation of acetylcholine seen in AD is associated with upregulation/hyperactivity of N-methyl-<smlcap>D</smlcap>-aspartate receptor (NMDAR). The hyperactivation of NMDAR then induces inflammation, which, in turn, causes AA to appear endogenously. Based on this hypothesis, we commented that cholinesterase inhibitors (ChEIs) are ‘preventative' therapy for AD and NMDAR antagonists are the true ‘treatment' for AD. We also noted that ChEIs, such as donepezil, could treat delirium. Moreover, we proposed measuring serum anticholinergic activity in patients, particularly AD patients, in out-of-hospital pharmacies to monitor the anticholinergic burden for targeted treatment.

The transition from vivid dreams over floccillations and visual hallucinations to complete delirium in a geriatric patient at the dawn of Alzheimer's dementia: beneficial role of rivastigmine

“…Most likely, the latter situation is presented here. The beneficial effect of rivastigmine to reduce delirium symptoms in our patient was in line with previous results in PD and stroke patients . However, a recent review casts doubt on a potent general AChI effect against delirium as in five of seven studies, there were no benefits for an AChI in either the prevention or the management of delirium .…”

“…The ‘behavioural continuum hypothesis’ in Parkinson's disease (PD) suggests that delirium due to antiparkinsonian agents starts with sleep disturbances, being followed by vivid dreams, which can progress to visual hallucinations (VH) and/or delusions further to delirium . Acetylcholinesterase inhibitors (AChI) have been shown to control all these conditions, suggesting a central cholinergic deficit (CCD) to be critically involved in the susceptibility of PD patients to develop delirium . Here, we provide further evidence for the ‘behavioural continuum hypothesis of delirium’ (BCHD) even in a geriatric patient with a non‐PD neurodegenerative disorder.…”

“…brain amyloid burden) and, moreover, intermittent hypoxia/re‐oxygenation was demonstrated to increase extra‐ and intracellular levels of beta‐amyloid in mice brains . Such proteins were strongly related to subsequently progressing CCD which promotes cognitive deficits including disturbed sleep‐wake cycle as well as reduced vigilance, alertness, attention and memory in patients with AD, delirium and the interface of both . Most likely, the latter situation is presented here.…”

“…1 Acetylcholinesterase inhibitors (AChI) have been shown to control all these conditions, suggesting a central cholinergic deficit (CCD) to be critically involved in the susceptibility of PD patients to develop delirium. 1,2 Here, we provide further evidence for the 'behavioural continuum hypothesis of delirium' (BCHD) even in a geriatric patient with a non-PD neurodegenerative disorder. A 79-year-old White man with obstructive sleep apnoea (OSA) and chronic kidney disease (CKD) was admitted due to increasing daytime napping with arousal gestures (floccillations, resp.…”

“…In accordance with BCHD, this senior (who was susceptible to AD) had experienced a gradual progression from vivid dreams over periods with daytime hypersomnia, floccillations and VH, finally culminating in a complete delirium. This progression depended on the severity of several co‐morbid stressors (CKD, OSA, benzodiazepine withdrawal and finally, sepsis).…”