Cognitive enhancers for dementia: Do they work?

Effects on functioning and behavior

In a 24-week multinational clinical trial, patients receiving donepezil (10 mg/d) were more able than placebo-treated patients to perform complex daily functioning tasks.²² Similar effects have been observed with rivastigmine and galantamine.^{16, 20}

All 3 AChE inhibitors have demonstrated improvements in the behavioral changes associated with AD. Cummings et al²³ tested the hypothesis that behavioral disturbances are reported at significantly lower rates by caregivers of AD patients receiving donepezil, compared with a group of patients not receiving a drug for treatment of dementia. Donepezil patients were described as significantly less likely to be threatening, destroy property, and talk loudly, and significantly fewer were treated with sedatives.

Table 1

COMPARING THEAChE INHIBITORS

An open-label study by Weiner et al²⁴ examined the effects of donepezil on emotional and behavioral symptoms using the CERAD Behavior Rating Scale for Dementia and its subscales. In a group of 25 AD patients treated with donepezil, scores returned to baseline levels at 12 months. In contrast, the scores of the reference group worsened minimally.

Galantamine has also proved effective in treating behavioral symptoms associated with AD. In the Tariot et al²⁰ study, galantamine at 16 mg/d and 24 mg/d had a significantly better outcome on CIBIC+, ADL, and behavioral symptoms versus placebo.

Rosler et al²⁵ assessed the ability of rivastigmine to improve behavioral symptoms in AD. Using the behavioral component of the CIBIC+, results showed that long-term treatment with rivastigmine could slow the progression of symptoms. Symptoms showing stabilization included aggressiveness, activity disturbances, hallucinations, and paranoid features. The results also suggest that patients treated earlier with rivastigmine may attain a greater benefit than those whose treatment is delayed 6 months.

Rivastigmine also has significant effects on controlling behavioral symptoms in patients with Lewy body dementia.²⁶ A placebo-controlled, double-blind, multicenter study was performed in 120 patients with Lewy body dementia. Individuals were given up to 12 mg/d rivastigmine or placebo for 20 weeks, followed by 3 weeks rest. Assessment by neuropsychiatric inventory was made at baseline, and again at weeks 12, 20, and 23.

Patients taking rivastigmine were significantly less apathetic and anxious than those on placebo, and had fewer delusions and hallucinations. Almost twice as many patients on rivastigmine as on placebo (37, 63% versus 18, 30%) showed at least a 30% improvement from baseline. In a computerized cognitive assessment system and neuropsychological tests, patients were significantly faster and better than those on placebo, particularly when performing tasks with a substantial attentional component.

Cost effectiveness

Numerous studies have demonstrated that AChE inhibitors are cost savers in AD treatment. Fillit et al²⁷ examined the impact of donepezil in a multisite managed care organization for 2 years using claims data for 70 individuals with AD and related dementias. The median per diem medical costs were $1.22 lower post treatment than they were in the pretreatment phase. Moreover, posttreatment costs were reduced in 6 of 7 service settings, with median per diem savings of $0.77 in outpatient care and $0.65 in office visits.

Neumann et al²⁸ utilized cost-effectiveness analysis to predict that for mild AD, donepezil would pay for itself in cost offsets if the drug’s effect exceeds 2 years. Donepezil costs were partially offset by a reduction in the costs of care due to enhanced cognitive functioning and the delay in placing the patient in more costly disease stages and settings.

One study used the disease-progression model to estimate potential per-patient savings resulting from the treatment of AD in Canada.²⁹ Rivastigmine was estimated to delay the transition to more severe stages of AD by up to 188 days for patients with mild AD after 2 years of treatment. For patients with mild-to-moderate and moderate disease, this delay was estimated to be 106 and 44 days, respectively.

The Assessment of Health Economics in Alzheimer’s Disease model uses algorithms to predict the time until patients with AD require full-time care. A study, performed in Canada, compared treatment with galantamine to treatment without pharmacological interventions.³⁰ Galantamine was predicted to reduce the duration of full-time care by almost 10%. Approximately 5.6 patients with mild-to-moderate disease must be placed on treatment to avoid 1 year of full-time care, resulting in savings averaging $528 per patient. For patients with moderate disease, 3.9 patients must be placed on treatment to avoid 1 year of full-time care, with savings predicted at $2,533 per patient.