Cholinesterase inhibitors for dementia

Treatment with cholinesterase inhibitors produces statistically significant but clinically marginal improvement in cognitive function in people with mild to severe dementia treated for periods of maximum one year.

A Cochrane review included 13 studies with a total of 7 298 subjects with Alzheimer's disease. The combined results of 10 placebo controlled trials demonstrate that treatment for 6 months with the cholinesterase inhibitors (ChEI) donepezil, galantamine or rivastigmine at the recommended dose produced improvements in cognitive function on average –2.7 points (95% CI –3.0 to –2.3), in the midrange of the 70 point ADAS-Cog Scale, for people with mild, moderate or severe Alzheimer's disease. Study clinicians rated global clinical state more positively in treated patients. Benefits of treatment were also seen on measures of activities of daily living and behaviour. None of these treatment effects are large. The effects are similar for patients with severe dementia, but there is evidence only from two trials. More patients leave ChEI treatment groups, 29%, on account of adverse events than leave the placebo groups (18%).

A systematic review including 59 RCTs was abstracted in DARE . The patients had Alzheimer disease (AD), vascular dementia (VD), Parkinson dementia (PD) or mild cognitive impairment (MCI); the majority of trials were of patients with AD. Most of the included trials were less than one year's duration (range 12 to 52 weeks).

• Donepezil vs. placebo (24 RCTs, n=7 556): A significant change in Alzheimer's Disease Assessment Scale cognitive subscale (ADAS-cog) scores was found in for donepezil (10 mg/daily) in patients with AD (all severity levels) (weighted mean difference [WMD] –2.80, 95% CI –3.28 to –2.33; 5 RCTs) and in patients with mild/moderate VD (WMD –2.17, 95% CI –2.99 to –1.34; 2 RCTs). No significant difference was found in MCI. RRs for improvement from baseline (RR 2.01, 95% CI 1.58 to 2.57; 3 RCTs) and improvement or stabilisation from baseline (RR 1.50, 95% CI 1.20 to 1.89; 1 RCT) in patients with AD (all severity levels, based on the clinician-based impression of change [CIBIC-plus]) were in favour of donepezil. No significant difference was found on the CIBIC-plus in patients with mild/moderate VD. Borderline statistical significance was found in favour of donepezil for ADLs in patients with VD (WMD-0.78, 95% CI –1.58 to 0.01; 2 RCTs).
• Rivastigmine vs. placebo (9 RCTs, n=2 164): Significant statistical improvement on the ADAS-cog was found for rivastigmine (6 mg/daily and 12 mg/daily) in patients with AD (all severity levels) (WMD –3.91, 95% CI –5.48 to –2.34). A significant improvement from baseline on the CIBIC-plus in favour of treatment was found when compared with placebo for patients with AD (all severity levels) (RR 1.76, 95% CI 1.35 to 2.29; 3 RCTs). One study looked at improvement or stabilisation on the same scale in the same patient group but no significant difference was found. Statistically significant effect in favour of rivastigmine was found on the Nurses Observation Scale for Geriatric Patients mood subscale (NOSGER-mood) (WMD 3.75, 95% CI 2.66 to 4.85) and the geriatric depression Scale (GDS) (WMD 0.22, 95% CI 0.15 to 0.28).
• Galantamine vs. placebo (10 RCTs, n=3 997): Significant improvement on the ADS-cog score was found for galantamine (24 mg/daily) in patients with mild/moderate AD (WMD –2.45, 95% CI –3.48 to –1.42; 6 RCTs) and in patients with AD and VD (WMD –2.70, 95% CI –3.95 to –1.45; 1 RCT). The RR for improvement or stabilisation from baseline (CIBIC-plus) was statistically significant in patients with mild/moderate AD (RR 1.22, 95% CI 1.12 to 1.33; 4 RCTs) and mild/moderate AD or VD (RR 1.25, 95% CI 1.08 to 1.45; 1 RCT). A significant improvement in ADLs was found in favour of galantamine in patients with AD (all severity) (WMD 1.84, 95 % CI 0.68 to 3.00).

Ədəbiyyat

1. Birks J. Cholinesterase inhibitors for Alzheimer's disease. Cochrane Database Syst Rev 2006 Jan 25;(1):CD005593.
2. Raina P, Santaguida P, Ismaila A, Patterson C, Cowan D, Levine M, Booker L, Oremus M. Effectiveness of cholinesterase inhibitors and memantine for treating dementia: evidence review for a clinical practice guideline. Ann Intern Med 2008 Mar 4;148(5):379-97.