Neuropsychiatric Symptoms and Cholinergic Therapy for Alzheimer’s Disease

Abstract

Neuropsychiatric abnormalities, as well as the commonly associated neuropsychological symptoms, are clinical characteristics of Alzheimer’s disease (AD), the most common form of dementia. Thus, in addition to a general cognitive and functional decline, neuropsychiatric manifestations, such as agitation, apathy, anxiety, psychoses and disinhibition, are frequently evident in AD patients. Such neuropsychiatric symptoms of AD are the source of considerable patient and caregiver distress, resulting in the prescription of neuroleptics, benzodiazepines or other psychotropic agents, and are a major factor in the decision to transfer the care of patients into nursing homes. Recent evidence suggests that some neuropsychiatric changes associated with AD are related to the cholinergic deficits in the brains of AD patients and that such abnormalities may be responsive to cholinergic therapy. Cholinergic drug therapies indicated for the symptomatic treatment of AD, for example tacrine and the newer cholinesterase (ChE) inhibitors such as donepezil, have been demonstrated to improve memory, language and praxis. Furthermore, although less is known about the effect of ChE inhibitors on the neuropsychiatric symptoms of AD, preliminary evidence suggests that they reduce apathy, anxiety, hallucinations, disinhibition and aberrant motor behaviour. Thus, the newer-generation ChE inhibitors that are well tolerated, easy to administer and show promise in reducing the cognitive, as well as neuropsychiatric disturbances of AD, may emerge as important treatments for some neuropsychiatric symptoms in patients with central cholinergic deficits, including AD.

Differential Involvement of 5-HT1B/1D and 5-HT6 Receptors in Cognitive and Non-cognitive Symptoms in Alzheimer's Disease

“…However, it is important to note that while cognitive syndromes deteriorate progressively over the course of AD, many of the behavioral syndromes occur episodically and in subgroups of patients during the disease (Sweet et al, 2000). This implies that the neurological basis of the behavioral changes of AD is dynamic and more consistent with a functional biochemical rather than a static structural cause (Levy et al, 1999). In this sense, the 5-HT 6 /ChAT ratio was related to aggressive behavior, both in BA10 and BA20.…”

“…In addition to these cognitive symptoms, most patients will suffer from neuropsychiatric symptoms called 'behavioral and psychological symptoms of dementia' (BPSD) (IPA, 1996). BPSD such as depression, overactivity, psychosis, or aggressive behavior occur frequently in AD patients and are the major factor that leads to early institutionalization of the patient (Levy et al, 1999;Martinson et al, 1995;Parnetti et al, 2001). BPSD are not merely an epiphenomenon of cognitive impairment, but could be attributed to specific biological brain dysfuction.…”

Cholinesterase Inhibitors as a Treatment for Post-Stroke Anxiety: A Case Report

“…To our knowledge, this is the first published report of post-stroke anxiety improving with an acetylcholinesterase inhibitors. They have been used in Alzheimer's disease to compensate for a cholinergic deficit and have been shown to improve anxiety symptoms in those with dementia [11,12]. Thus, it seems plausible that acetylcholinesterase inhibitors may be a possible treatment avenue to further explore in some individuals with post-stroke anxiety related to cognitive impairment.…”

Prescribing patterns for psychotic and behavioural symptoms in dementia: a national survey

“…In particular, cyproterone acetate has been suggested in sexual disinhibition (Harris & Wier, 1998). It has also been proposed that cholinergic drugs may be beneficial in this area (Levy et al, 1999).…”