Alzheimer Disease: Mohan M

Mohan M, Bennett C, Carpenter PK. · Department of Neuropsychiatry, Neuropsychology and Epileptology, Burden Centre, North Bristol Trust, Frenchay Hospital, Bristol, Avon, UK, BS16 1JB. · Cochrane Database Syst Rev. · Pubmed #19160344 No free full text.

Abstract: BACKGROUND: Alzheimer's dementia (AD) is the most common form of dementia in people with Down Syndrome (DS). Acetylcholine is a chemical found in the brain that has an important role in memory, attention, reason and language. Rivastigmine is a "pseudo-irreversible" inhibitor of acetylcholinesterase, which is thought to maintain levels of acetylcholine. Rivastigmine can improve cognitive function and slow the decline of AD in the general population over time. It is important to note that people with DS tend to present with AD at a much younger age than the normal population as well as having subtle differences in physiology (e.g. metabolism and heart rate) and may therefore have different requirements from the general population. OBJECTIVES: To determine the effectiveness and safety of rivastigmine for people with DS who develop AD. SEARCH STRATEGY: CENTRAL, MEDLINE, EMBASE, CINAHL, PsycINFO, BIOSIS, SCI, SSCI and the NRR were searched up to October 2008. We contacted the manufacturers of rivastigmine as well as experts in the field, to ask about reports of unpublished or ongoing trials. SELECTION CRITERIA: Randomised controlled trials of participants with DS and AD in which treatment with rivastigmine was administered compared with a placebo group. DATA COLLECTION AND ANALYSIS: No study was identified which met inclusion criteria for this review. MAIN RESULTS: No study was identified which met inclusion criteria for this review. AUTHORS' CONCLUSIONS: As there are no included trials, recommendations cannot be made about rivastigmine for AD in DS. Well-designed, adequately powered studies are required.

Mohan M, Bennett C, Carpenter PK. · Department of Neuropsychiatry, Neuropsychology and Epileptology, Burden Centre, North Bristol Trust, Frenchay Hospital, Bristol, Avon, UK, BS16 1JB. · Cochrane Database Syst Rev. · Pubmed #19160343 No free full text.

Abstract: BACKGROUND: Alzheimer's dementia (AD) is the most common form of dementia in people with Down Syndrome (DS). There is an understanding that an increase in L-glutamate contributes to the pathogenesis of cerebral ischemias and AD. Memantine acts as an antagonist of N-methyl-D-aspartate (NMDA) type receptors, which is thought to reduce abnormal activation of glutamate neurotransmission. It binds with a low affinity to the NMDA receptor and so should not prevent learning and the formation of memory. Memantine can improve cognitive function and slow the decline of AD in the general population over time, and is the subject of this review. It is important to note that people with DS tend to present with AD at a much younger age than the normal population as well as having subtle differences in physiology (e.g. metabolism and heart rate) and may therefore have different requirements from the general population. OBJECTIVES: To determine the effectiveness and safety of memantine for people with DS who develop AD. SEARCH STRATEGY: CENTRAL, MEDLINE, EMBASE, CINAHL, PsycINFO, BIOSIS, SCI, SSCI and the NRR were searched up to October 2008. We contacted the manufacturers of memantine, as well as experts in the field, to ask about reports of unpublished or ongoing trials. SELECTION CRITERIA: Randomised controlled trials of participants with DS and AD in which treatment with memantine was administered compared with a placebo group. DATA COLLECTION AND ANALYSIS: No study was identified which met the inclusion criteria for this review. MAIN RESULTS: No study was identified which met inclusion criteria for this review, however there is an on-going randomised controlled study being conducted in the UK and data are expected in 2009. AUTHORS' CONCLUSIONS: As there are no included trials, recommendations cannot be made about memantine for AD in DS. Well-designed, adequately powered studies are required.

Mohan M, Bennett C, Carpenter PK. · Department of Neuropsychiatry, Neuropsychology and Epileptology, Burden Centre, North Bristol Trust, Frenchay Hospital, Bristol, Avon, UK, BS16 1JB. · Cochrane Database Syst Rev. · Pubmed #19160342 No free full text.

Abstract: BACKGROUND: Alzheimer's dementia (AD) is the most common form of dementia in people with Down Syndrome (DS). Acetylcholine is a chemical found in the brain that has an important role in memory, attention, reason and language. Galantamine both inhibits the activity of acetylcholinesterase and increases the level of acetylcholine. Galantamine can improve cognitive function and slow the decline of AD in the general population over time. It is important to note that people with DS tend to present with AD at a much younger age than the normal population as well as having subtle differences in physiology (e.g. metabolism and heart rate) and may therefore have different requirements from the general population. OBJECTIVES: To determine the effectiveness and safety of galantamine for people with DS who develop AD. SEARCH STRATEGY: CENTRAL, MEDLINE, EMBASE, CINAHL, PsycINFO, BIOSIS, SCI, SSCI and the NRR were searched up to October 2008. We contacted the manufacturers of galantamine as well as experts in the field, to ask about reports of unpublished or ongoing trials. SELECTION CRITERIA: Randomised controlled trials of participants with DS and AD in which treatment with galantamine was administered compared with a placebo group. DATA COLLECTION AND ANALYSIS: No study was identified which met inclusion criteria for this review. MAIN RESULTS: No study was identified which met inclusion criteria for this review. AUTHORS' CONCLUSIONS: As there are no included trials, recommendations cannot be made about galantamine for AD in DS. Well-designed, adequately powered studies are required.

Mohan M, Carpenter PK, Bennett C. · Department of Neuropsychiatry, Neuropsychology and Epileptology, Burden Centre, North Bristol Trust, Frenchay Hospital, Bristol, Avon, UK, BS16 1JB. · Cochrane Database Syst Rev. · Pubmed #19160328 No free full text.

Abstract: BACKGROUND: Alzheimer's dementia (AD) is the most common form of dementia in people with Down Syndrome [DS]. Acetylcholine is a chemical found in the brain that has an important role in memory, attention, reason and language. Donepezil a reversible inhibitor of acetylcholinesterase, which is thought to maintain levels of acetylcholine, and is reported to have some benefits for people with AD in the general population. It is important to note that people with DS tend to present with AD at a much younger age than the normal population as well as having subtle differences in physiology (e.g. metabolism and heart rate) and may therefore have different requirements from the general population. OBJECTIVES: To determine the effectiveness and safety of donepezil for people with DS who develop AD. SEARCH STRATEGY: CENTRAL, MEDLINE, EMBASE, CINAHL, PsycINFO, BIOSIS, SCI, SSCI and the NRR were searched up to October 2008. We contacted the manufacturers of donepezil as well as experts in the field, to ask about reports of unpublished or ongoing trials. SELECTION CRITERIA: Randomised controlled trials of participants with DS and AD in which treatment with donepezil was administered compared with a placebo group. DATA COLLECTION AND ANALYSIS: Data were extracted from the published reports of the one relevant study identified. MAIN RESULTS: The one study included in this review is a small (n=30) randomised controlled trial lasting 24 weeks. It was followed-up by an open label study with a crossover design.No significant differences were found on any four validated outcomes including global functioning and three measures of cognitive abilities and behavioural problems. 6 out of 16 carers (37%) of participants on donepezil and 2 out of 15 (13%) on placebo reported improvement. No data were available for day to day skills, institutionalisation, reduction in carers' stress or economic outcomes. Half the intervention group and 20% of the placebo group reported adverse events; two participants left because of adverse events. AUTHORS' CONCLUSIONS: To date there is only one small randomised controlled study on the effect of donepezil. This shows, at best, a modest, non statistically significant trend in favour of people with Down syndrome and Alzheimer's dementia who are able to tolerate donepezil (this drug is currently only dispensed in relatively large doses and is contraindicated for those with cardiac and respiratory problems).This study does not provide good evidence on which to base practice. Findings in an open-label follow up to this study suggest possible benefit in some individuals. Further, larger randomised controlled studies with longer-term follow up are required.