Beyond the Cholinergic Hypothesis: The Effect of Metrifonate and Other Cholinesterase Inhibitors on Neuropsychiatric Symptoms in Alzheimer’s Disease

125

Fundamental and therapeutic research in Alzheimer’s disease (AD) focused for a long time exclusively on cognitive aspects. However, AD also frequently involves complex disorders of affect and behavior, which are currently grouped under the heading ‘behavioral and psychological signs and symptoms of dementia’ (BPSSD). Several rating tools have been developed over the years on the basis of a variety of source data. Some are derived from psychiatric practise or have specifically been developed for dementia, such as the Neuropsychiatric Inventory (NPI). In this study we prospectively used the NPI to examine BPSSD. Sixty-three French patients (mean age 74.7 years, SD 7.9) with a Mini-Mental State Examination (MMSE) score higher than 10 were examined. BPPSD were detected by NPI in 95.2% of the patients. Anxiety was the most common abnormality (65.1%), followed by apathy and dysphoria (58.7%). The highest frequency × severity NPI score was observed for apathy. In order to identify the relationship between regional cerebral perfusion and apathy, 20 of these AD patients underwent a technetium-99m-bicisate SPECT protocol within the same week as the NPI evaluation. The mean age of this population was 74.4 years (SD 5.3) and the mean MMSE score was 21 (SD 4.1). The apathy NPI score was correlated with right cingulate deficit whereas the highest correlation for the MMSE was with the left temporoparietal area. This stresses the interest to focus on SPECT imaging of AD patients not only in the posterior areas.

Section: Discussionmentioning

confidence: 99%

Behavioral and Psychological Symptoms in Alzheimer’s Disease

Benoît

Dygai

Migneco

et al. 1999

125

“…Kaufer [45] and Dubois et al [46] both studied the effect of metrifonate in patients with AD. The former reported a significant improvement in apathy (NPI apathy item) in 408 patients treated with metrifonate compared with placebo (p = 0.03) [45] , whereas in the latter study (n = 605), a significant improvement (p = 0.048, compared with placebo) in the NPI apathy score of patients treated with a high (60-80 mg) but not low (40-50 mg) dose of metrifonate was reported [46] .…”

Section: Rctsmentioning

confidence: 99%

Pharmacological Treatment of Apathy in Neurodegenerative Diseases: A Systematic Review

Drijgers¹,

Aalten²,

Winogrodzka

et al. 2009

Objective: To evaluate the efficacy of pharmacological treatment of apathy in patients with neurodegenerative diseases. Methods: Systematic review of studies assessing the effects of pharmacological treatment on apathy in neurodegenerative diseases. Results: Thirty-five studies were included: 2 meta-analyses, 13 randomized controlled trials (RCTs), 14 open-label studies, 5 case series, and 1 single case study. Eight studies included apathy as a primary outcome. A cholinesterase inhibitor was investigated in 24 studies, methylphenidate in 5, and other medications in 6 studies. Most RCTs of cholinesterase inhibitors reported a small but statistically significant improvement of apathetic symptoms. Conclusions: Although some medications are promising candidates for further study, there is as yet insufficient evidence that pharmacological treatment improves apathetic symptoms in patients with neurodegenerative disease. Large-scale, placebo-controlled RCTs with apathy as a primary outcome measure are needed to establish the potential benefit of pharmacological treatment of apathy.

“…Nevertheless, such symptomatic treatments represent one potential route to cost containment [13]. Clinical studies have shown that ChE inhibitors have benefits in terms of global function, cognitive function and ADLs for up to at least 1 year in patients with mild to moderate AD [14][15][16][17][18][19][20] and may also have potential benefits for certain behavioural symptoms [21][22][23][24]. Donepezil, for example, is a secondgeneration, piperidine-based molecule and specific inhibitor of the centrally acting acetylcholinesterase (as opposed to butyrylcholinesterase, which acts mainly in the periphery) which has been available for clinical use in France since 1998.…”

Section: Introductionmentioning

confidence: 99%

Donepezil for the Treatment of Mild to Moderate Alzheimer’s Disease in France: The Economic Implications

Fagnani

Lafuma²,

Pechevis³

et al. 2003

In the present study, the socioeconomic impact of the use of the acetylcholinesterase inhibitor donepezil in patients with mild to moderate Alzheimer’s disease (AD) living in France was examined. A model was created to extrapolate over a 3-year period the results from placebo-controlled trials together with epidemiological and prevalence data. Costs considered in the model were net societal costs associated with paid and unpaid assistance, general medical consumption and institutional care. The model suggested that delays in cognitive decline and functional dependence due to treatment reduced the time spent in institutional care and the burden on caregivers. Over a 3-year period, total net costs of caring for untreated patients with an initial Mini-Mental State Examination score ranging from 10 to 26 were EUR 53,206 compared with EUR 42,720 for a patient treated with donepezil – an annual cost saving of approximately EUR 3,500 per patient. Cost savings were mainly due to savings in unpaid caregiver time, which, apart from patient institutionalization, represented the most costly component of total care in this study but had no direct budgetary impact. Overall, these data suggest that donepezil is a cost-effective treatment for mild to moderately impaired AD patients living in France.