title: Pharmacological interventions for cognitive decline in people with Down syndrome.
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.
  
  
  OBJECTIVE
  To assess the effectiveness of anti-dementia pharmacological interventions and nutritional supplements for treating cognitive decline in people with Down syndrome.
  
  
  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.
  
  
  METHODS
  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.
  
  
  METHODS
  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.
  
  
  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.
  
  
  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.
authors.affiliation: School of Sociology, Social Policy and Social Work, Queen's University Belfast, 6 College Park, Belfast, UK, BT7 1LP.
authors.forename: Nuala
authors.initials: N
authors.lastname: Livingstone
authors.forename: Jennifer
authors.initials: J
authors.lastname: Hanratty
authors.forename: Rupert
authors.initials: R
authors.lastname: McShane
authors.forename: Geraldine
authors.initials: G
authors.lastname: Macdonald
mesh_terms: D000108:Acetylcarnitine / Q000009:adverse effects / Q000627:therapeutic use; D000328:Adult; D000975:Antioxidants / Q000627:therapeutic use*; D003071:Cognition / Q000187:drug effects; D003072:Cognition Disorders / Q000188:drug therapy*; D000077265:Donepezil; D004314:Down Syndrome / Q000150:complications*; D006801:Humans; D007189:Indans / Q000009:adverse effects / Q000627:therapeutic use; D008559:Memantine / Q000009:adverse effects / Q000627:therapeutic use; D008875:Middle Aged; D018697:Nootropic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D010880:Piperidines / Q000009:adverse effects / Q000627:therapeutic use; D016032:Randomized Controlled Trials as Topic; D019821:Simvastatin / Q000009:adverse effects / Q000627:therapeutic use
chemical_list: D000975:Antioxidants; D007189:Indans; D018697:Nootropic Agents; D010880:Piperidines; D000108:Acetylcarnitine; D000077265:Donepezil; D019821:Simvastatin; D008559:Memantine