Cholinesterase Inhibitors for Rarer Dementias Associated with Neurological Conditions

Summary

A Cochrane review [Abstract] 1 included 8 studies with a total of 567 subjects. Six studies used a simple parallel-group design; the other two consisted of an open-label treatment period followed by a randomised phase. The cholinesterase inhibitors (ChI) used were donepezil, rivastigmine and galantamine. All trials used placebo as control.

• Huntington's disease (2 trials, n=42): One study (n=24) found that ChI use in the short-term (12 weeks) had no statistically significant impact on the cognitive portion of the Alzheimer Disease Assessment Scale (ADAS-Cog; WMD 1.00, 95% CI -1.66 to 3.66, p=0.46), Unified Huntington's Disease Rating Scale (UHDRS) Verbal Fluency Test (WMD -1.20, 95% CI -7.97 to 5.57, p=0.73), UHDRS Symbol Digit Modalities Test (SDMT; WMD 2.70, 95% CI -0.95 to 6.35, p=0.15) and other psychometric tests. The other study (n=18) found that ChI use in the medium-term (6 months) improved the results of the verbal fluency test (WMD 6.43, 95% CI 0.66 to 12.20, p=0.03) and California Verbal Learning Test - Second Edition (CVLT-II) Recognition Task (WMD 2.42, 95% CI 0.17 to 4.67, p=0.04). There was no statistically significant difference between groups on the SDMT (WMD -0.31, 95% CI -7.77 to 7.15, p=0.94), CVLT-II trials 1-5 (WMD -2.09, 95% CI -11.65 to 7.47, p=0.67), short-delay recall (WMD 0.35, 95% CI -2.87 to 3.57, p=0.83), or long-delay recall (WMD -0.14, 95% CI -3.08 to 2.80, p=0.93), and other psychometric tests.
• Multiple sclerosis(4 trials, n=335): One study (n=60) found no differences between the ChI (short-term: 12 weeks) and placebo groups on the Wechsler Memory Scales general memory score (WMD 0.90, 95% CI -0.52 to 2.32, p=0.22). The 3 other trials found that in the medium-term (16 to 24 weeks) ChI's improved the clinician's impression of cognitive change (OR 1.96, 95% CI 1.06 to 3.62, p=0.03; 2 studies). However, the treatment effect on other aspects of cognitive change were unclear, measured by the Selective Reminding Test (WMD 1.47, 95% CI -0.39 to 3.32, p=0.12; 3 studies, n=275), patient's self-reported impression of memory change (OR 1.67, 95% CI 0.93 to 3.00, p=0.08; 2 studies) and cognitive change (OR 0.95, 95% CI 0.45 to 1.98, p=0.89; 1 study), clinician's impression of memory change (OR 1.50, 95% CI 0.59 to 3.84, p=0.39; 1 study), other psychometric tests, and activities of daily living - patient reported impact of multiple sclerosis activities (WMD -1.18, 95% CI -3.02 to 0.66, p=0.21; 1 study).
• Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) (1 study, n=168): this study found during an 18-week follow-up a beneficial effect of ChI's on the Executive interview, and Trail Making Test parts A and B. The impact of ChI's on the Vascular ADAS-Cog score (WMD 0.04, 95% CI -1.57 to 1.65, p=0.96), the Clinical Dementia Rating Scale Sum of Boxes (WMD -0.09, 95% CI -0.48 to 0.03, p=0.65) Disability Assessment for Dementia scale (WMD 0.58, 95% CI -2.72 to 3.88, p=0.73), and other measures was unclear.
• Frontotemporal dementia (FTD) (1 study, n=39): This trial consisted of an open-label treatment period followed by a randomised, double-blind, placebo-controlled phase. No data of primary outcomes were reported in this study.

In the included studies, the most common side effect was gastrointestinal symptoms. For all conditions, compared to the treatment group, the placebo group experienced significantly less nausea (44/257 vs. 22/246, OR 2.10, 95% CI 1.22 to 3.62, p=0.007; 6 studies), diarrhoea (40/257 vs. 13/246, OR 3.26, 95% CI 1.72 to 6.19, p=0.0003; 6 studies) and vomiting (17/192 vs. 3/182, OR 5.76, 95% CI 1.67 to 19.87, p=0.006; 3 studies).