Abstract
Background
People with Down syndrome are vulnerable to developing dementia at an earlier age than the general population. Alzheimer’s disease and cognitive decline in people with Down syndrome can place a significant burden on both the person with Down syndrome and their family and carers. Various pharmacological interventions, including donepezil, galantamine, memantine and rivastigmine, appear to have some effect in treating cognitive decline in people without Down syndrome, but their effectiveness for those with Down syndrome remains unclear.
Objectives
To assess the effectiveness of anti-dementia pharmacological interventions and nutritional supplements for treating cognitive decline in people with Down syndrome.
Search methods
In January 2015, we searched CENTRAL, ALOIS (the Specialised Register of the Cochrane Dementia and Cognitive Improvement Group), Ovid MEDLINE, Embase, PsycINFO, seven other databases, and two trials registers. In addition, we checked the references of relevant reviews and studies and contacted study authors, other researchers and relevant drug manufacturers to identify additional studies.
Selection criteria
Randomised controlled trials (RCTs) of anti-dementia pharmacological interventions or nutritional supplements for adults (aged 18 years and older) with Down syndrome, in which treatment was administered and compared with either placebo or no treatment.
Data collection and analysis
Two review authors independently assessed the risk of bias of included trials and extracted the relevant data. Review authors contacted study authors to obtain missing information where necessary.
Main results
Only nine studies (427 participants) met the inclusion criteria for this review. Four of these (192 participants) assessed the effectiveness of donepezil, two (139 participants) assessed memantine, one (21 participants) assessed simvastatin, one study (35 participants) assessed antioxidants, and one study (40 participants) assessed acetyl-L-carnitine.
Five studies focused on adults aged 45 to 55 years, while the remaining four studies focused on adults aged 20 to 29 years. Seven studies were conducted in either the USA or UK, one between Norway and the UK, and one in Japan. Follow-up periods in studies ranged from four weeks to two years. The reviewers judged all included studies to be at low or unclear risk of bias.
Analyses indicate that for participants who received donepezil, scores in measures of cognitive functioning (standardised mean difference (SMD) 0.52, 95% confidence interval (CI) -0.27 to 1.13) and measures of behaviour (SMD 0.42, 95% CI -0.06 to 0.89) were similar to those who received placebo. However, participants who received donepezil were significantly more likely to experience an adverse event (odds ratio (OR) 0.32, 95% CI 0.16 to 0.62). The quality of this body of evidence was low. None of the included donepezil studies reported data for carer stress, institutional/home care, or death.
For participants who received memantine, scores in measures of cognitive functioning (SMD 0.05, 95% CI -0.43 to 0.52), behaviour (SMD -0.17, 95% CI -0.46 to 0.11), and occurrence of adverse events (OR 0.45, 95% CI 0.18 to 1.17) were similar to those who received placebo. The quality of this body of evidence was low. None of the included memantine studies reported data for carer stress, institutional/home care, or death.
Due to insufficient data, it was possible to provide a narrative account only of the outcomes for simvastatin, antioxidants, and acetyl-L-carnitine. Results from one pilot study suggest that participants who received simvastatin may have shown a slight improvement in cognitive measures.
Authors’ conclusions
Due to the low quality of the body of evidence in this review, it is difficult to draw conclusions about the effectiveness of any pharmacological intervention for cognitive decline in people with Down syndrome.
Plain language summary
Medications for cognitive decline in people with Down syndrome
People with Down syndrome often experience cognitive decline (a deterioration in memory, language, thinking and judgment that are greater than normal age-related changes) at a younger age and in greater numbers than the general population. Various medicines have been shown to improve, or at least slow down the progression of these symptoms in people without Down syndrome.
Review question
Do adults (18 years and older) with Down syndrome benefit from treatment with medicine to prevent cognitive decline, compared with other adults with Down syndrome who receive either fake medicine (placebos) or no medicine?
Study characteristics
In January 2015, we, a team of Cochrane researchers, searched for all medical studies that investigated the effect of any medicine or nutritional supplement on cognitive decline in adults with Down syndrome. We found nine relevant randomised controlled trials (this design produces the most reliable results) that we could include in this overview. These studies tested:
– donepezil, a medicine used to treat Alzheimer’s disease (four studies);
– memantine, a medicine used to treat Alzheimer’s disease (two studies);
– simvastatin, a (statin) medicine used to prevent heart disease (one study);
– a mixture of antioxidants, including forms of vitamins C and E, and alpha-lipoic acid (one study); and
– acetyl-L-carnitine, a dietary supplement that has previously been used to treat dementia (one study).
Five of the studies focused on adults aged 45 to 55 years and four focused on adults aged 20 to 29 years. Seven studies were conducted in either the USA or UK, one took place in Norway and the UK, and one study was conducted in Japan.
Key results
The nine studies we found examined the effects of five medicines that are, or have been, used to prevent cognitive decline. All the studies compared the medicine being tested with a placebo (a tablet or capsule that looked and tasted like the medicine, but which contained no medicine).
Generally, those who received the medicine did no better than those who received the placebo in any of the areas assessed in the studies. The areas assessed included general functioning (including memory and thinking, speech, mood and behaviour); cognitive functioning (including memory, following what’s going on around you); adaptive behaviours (being able to do day-to-day tasks); or behaviour problems (such as being irritable or aggressive).
The only medicine to show any positive effect was the statin, simvastatin. Preliminary findings from a very small study showed that simvastin had some benefit on improving memory compared to placebo.
In the four donepezil studies, those participants given donepezil reported more headaches, dizziness, and nausea than participants given placebo. In the two memantine studies, there was no difference between participants given memantine or placebo for reports of headaches, dizziness, and nausea.
Quality of the evidence
Although the included studies were well conducted, most involved small numbers of participants and for many of the areas assessed we could not combine results from two or more studies. Overall, the quality of this evidence is low. We cannot be certain whether any of these medicines are effective. Running more trials with more people over a longer period of time would allow us answer this question with greater certainty.
We could not find any trials that investigated many of the medicines used to prevent cognitive decline, and so research is needed to explore the effectiveness of these medications in the Down syndrome population.
