Donepezil for dementia in people with Down syndrome

Mohan, Monica; Carpenter, Peter; Bennett, Cathy

doi:10.1002/14651858.cd007178

Cited by 25 publications

(28 citation statements)

References 28 publications

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“…Only randomised controlled trials of participants with DS and AD were selected. The only study that met the inclusion criteria for donepezil (Mohan et al, 2009d ) showed, at best, a modest, not statistically signifi cant trend in favor of people with DS and AD. No study was identifi ed which met inclusion criteria for rivastigmine, galanamine and memantine (Mohan et al, 2009a,b,c ).…”

Section: Therapies For Dementia In Down Syndromementioning

confidence: 95%

Is it possible to improve neurodevelopmental abnormalities in Down syndrome?

Bartesaghi

Guidi²,

Ciani³

2011

Revneuro

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Down syndrome (DS) is a genetic pathology caused by the triplication of human chromosome 21. Although individuals with DS have various medical problems, intellectual disability is the most invalidating aspect of the pathology. Despite numerous efforts, the mechanisms whereby gene triplication leads to the DS phenotype have not been elucidated and there are, at present, no therapies to rescue brain developmental alterations and mental disability in individuals with DS. In this review, we focused on the major defects of the DS brain, comparing data regarding humans with DS and mouse models for DS, and therapeutic interventions attempted on animal DS models. Based on the promising results of pharmacotherapies in these models, we believe that it is possible to conclude that tools to improve brain development in DS are now almost at hand. We now know that it is possible to rescue and/or improve neurogenesis, neuron maturation, connectivity, neurodegeneration and behavior. We believe that the knowledge gained in DS mouse models provides a rational basis to start new clinical trials in infants, children and adults with DS, exploiting drugs that have proved able to rescue various facets of the DS neurologic phenotype. It is not unreasonable to consider that the results of these trials may provide a positive answer to the question: 'Is it possible to improve brain development in DS?'.

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Section: Therapies For Dementia In Down Syndromementioning

confidence: 95%

Is it possible to improve neurodevelopmental abnormalities in Down syndrome?

Bartesaghi

Guidi²,

Ciani³

2011

Revneuro

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“…In part, these results in the animal model led to trials of several different acetylcholinesterase inhibitors in adults with DS and dementia. However, in DS, there appears to be no consistent or compelling evidence for efficacy of acetylcholinesterase inhibitors including donepezil, galantamine, and rivastigmine in preventing the cognitive decline associated with dementia (Mohan et al, 2009a–d). Likewise, a trial of donepezil in children and adolescents with DS failed to demonstrate cognitive benefit (Kishnani et al, 2010).…”

Section: Altering the Neurological Phenotype Through Treatmentmentioning

confidence: 99%

Neurological phenotypes for Down syndrome across the life span

Lott

2012

Progress in Brain Research

198

158

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This chapter reviews the neurological phenotype of Down syndrome (DS) in early development, childhood, and aging. Neuroanatomic abnormalities in DS are manifested as aberrations in gross brain structure as well as characteristic microdysgenetic changes. As the result of these morphological abnormalities, brain circuitry is impaired. While an intellectual disability is ubiquitous in DS, there is a wide range of variation in cognitive performance and a growing understanding between aberrant brain circuitry and the cognitive phenotype. Hypotonia is most marked at birth, affecting gait and ligamentous laxity. Seizures are bimodal in presentation with infantile spasms common in infancy and generalized seizures associated with cognitive decline observed in later years. While all individuals have the characteristic neuropathology of Alzheimer's disease (AD) by age 40years, the prevalence of dementia is not universal. The tendency to develop AD is related, in part, to several genes on chromosome 21 that are overexpressed in DS. Intraneuronal accumulation of β-amyloid appears to trigger a cascade of neurodegeneration resulting in the neuropathological and clinical manifestations of dementia. Functional brain imaging has elucidated the temporal sequence of amyloid deposition and glucose metabolic rate in the development of dementia in DS. Mitochondrial abnormalities contribute to oxidative stress which is part of AD pathogenesis in DS as well as AD in the general population. A variety of medical comorbidities threaten cognitive performance including sleep apnea, abnormalities in thyroid metabolism, and behavioral disturbances. Mouse models for DS are providing a platform for the formulation of clinical trials with intervention targeted to synaptic plasticity, brain biochemistry, and morphological brain alterations.

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“…While some providers will use traditional pharmacologic agents to slow the rate of decline, multiple Cochrane reviews of pharmaceutical treatment for dementia in adults with Down's syndrome do not support this treatment owing to lack of evidence. [122][123][124][125] The largest trial of pharmaceutical intervention in adults with Down's syndrome and dementia used memantine, which showed no benefit and a trend toward worse behaviors in the treatment group. 122 Consequently, current recommendations focus on interventions to minimize caregiver burden, including respite care and creating an environment in which the patient can maintain function.…”

Section: Neurologymentioning

confidence: 99%