Donepezil Significantly Improves Abilities in Daily Lives of Female down Syndrome Patients with Severe Cognitive Impairment: A 24-Week Randomized, Double-Blind, Placebo-Controlled Trial

Kondoh, Tatsuro; Kanno, Atsushi; Itoh, Hiroshi; Nakashima, Makoto; Honda, Ryoko; Kojima, Masaaki; Noguchi, Mitsuru; Nakane, Hideyuki; Nozaki, Hideki; Sasaki, Hidetada; Nagai, Toshiro; Kosaki, Rika; Kakee, Naoko; Okuyama, Torayuki; Fukuda, Masafumi; Ikeda, Masayuki; Shibata, Yoshisada; Moriuchi, Hiroyuki

doi:10.2190/pm.41.1.g

Cited by 45 publications

(19 citation statements)

References 14 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…With the growing number of DS individuals living to older ages, there is an urgent need to find effective clinical and preclinical AD treatments in this vulnerable population. 41-44 …”

Section: Discussionmentioning

confidence: 99%

Florbetapir PET, FDG PET, and MRI in Down syndrome individuals with and without Alzheimer's dementia

Sabbagh

Chen

Rogers

et al. 2015

Alzheimer's & Dementia

View full text Add to dashboard Cite

Since Down syndrome (DS) is associated with amyloid β (Aβ) deposition, we characterized imaging measurements of regional fibrillar Aβ burden, cerebral metabolic rate (rCMRgl), gray matter volumes (rGMVs), and age associations in 5 DS with dementia (DS/AD+), 12 DS without dementia (DS/AD-), and 9 normal controls (NCs).There were significant group differences in mean SUVRs for florbetapir with DS/AD+ having the highest, followed by DS/AD-, followed by NC. For FDG-PET, posterior cingulate rCMRgl in DS/AD+ was significantly reduced compared to DS/AD- and NC. For vMRI, hippocampal volumes were significantly reduced for the DS/AD+ compared to DS/AD- and NC. Age-related SUVR increases and rCMRgl reductions were greater in DS participants than in NCs. DS is associated with fibrillar Aβ, rCMRgl, and l rGMV alterations in the dementia stage and prior to the presence of clinical decline. This study provides a foundation for the studies needed to inform treatment and prevention in DS.

show abstract

“…With the growing number of DS individuals living to older ages, there is an urgent need to find effective clinical and preclinical AD treatments in this vulnerable population. 41-44 …”

Section: Discussionmentioning

confidence: 99%

Florbetapir PET, FDG PET, and MRI in Down syndrome individuals with and without Alzheimer's dementia

Sabbagh

Chen

Rogers

et al. 2015

Alzheimer's & Dementia

View full text Add to dashboard Cite

show abstract

“…Aylward et al stated that behavioral changes such as withdrawal and apathy appear to be early signs of dementia and that the course of Alzheimer’s disease and these conditions are related to frontal lobe dysfunction and are characterized by the frequent occurrence of neurological disorders such as early-onset Alzheimer’s disease-type dementia 27–30. It has recently been demonstrated by Kondoh et al that donepezil, a drug often used in patients with Alzheimer’s disease, improves the activities of daily living in Down syndrome patients, including young adults with the abovementioned rapid and progressive deterioration of such activities 31. The latter report suggests that individuals with Down syndrome and acute neuropsychiatric disorder may respond favorably to medication with a drug (donepezil) used in patients with Alzheimer’s disease.…”

Section: Discussionmentioning

confidence: 99%

Acute neuropsychiatric disorders in adolescents and young adults with Down syndrome: Japanese case reports

Akahoshi

Matsuda²,

Funahashi³

et al. 2012

NDT

View full text Add to dashboard Cite

Background:The aim of this study was to evaluate acute neuropsychiatric disorders in adolescents and young adults with Down syndrome. We report 13 Japanese adolescents or young adults with Down syndrome who developed acute neuropsychiatric disorders including withdrawal, depression, obsessive-compulsive behaviors, and occasional delusions or hallucinations.Methods:The following information was collected from each patient: age at onset of acute neuropsychiatric disorder, complications, signs and symptoms, personality traits before the onset of the acute neuropsychiatric disorder, prescribed medications with their respective doses and the response to treatment, and senile changes observed on magnetic resonance imaging or computed tomography.Results:The mean age at onset of these disorders was 21.2 years. Brain imaging showed almost senile changes; patients responded well to low-dose psychotropic therapy. Patients had an onset at a young age and presented with treatable conditions, although the average age of the onset of Alzheimer’s disease is generally over 40 years of age in patients with Down syndrome.Conclusion:These findings suggest that the pathology of acute neuropsychiatric disorder in patients with Down syndrome may be related to presenile changes; however, these disorders present features and a clinical course that is different from those presented in typical Alzheimer’s disease with Down syndrome.

show abstract

“…Each of these drugs has shown minor yet significant improvements to cognition and global status in clinical studies of mild to moderate AD patients. In particular, four small clinical trials using Donepezil, which included individuals with DS-AD suggest beneficial effects, including decreased confusion and cognitive improvement, though these trials were short (often under 6 months) and all involved relatively few patients [185, 186]. Despite studies in animal models that indicate that AChE inhibitors may act to modulate APP processing away from the amyloidogenic pathway [187, 188], more prolonged treatment paradigms using AChE inhibitors in AD patients have not lead to sustainable improvement or marked reductions in progression of the AD disease process.…”

Section: Neuroprotection Trials In Micementioning

confidence: 99%

Cognitive Impairment, Neuroimaging, and Alzheimer Neuropathology in Mouse Models of Down Syndrome

Hamlett¹,

Boger²,

Ledreux³

et al. 2015

CAR

View full text Add to dashboard Cite

Down syndrome (DS) is the most common non-lethal genetic condition that affects approximately 1 in 700 births in the United States of America. DS is characterized by complete or segmental chromosome 21 trisomy, which leads to variable intellectual disabilities, progressive memory loss, and accelerated neurodegeneration with age. During the last three decades, people with DS have experienced a doubling of life expectancy due to progress in treatment of medical comorbidities, which has allowed this population to reach the age when they develop early onset Alzheimer’s disease (AD). Individuals with DS develop cognitive and pathological hallmarks of AD in their fourth or fifth decade, and are currently lacking successful prevention or treatment options for dementia. The profound memory deficits associated with DS-related AD (DS-AD) have been associated with degeneration of several neuronal populations, but mechanisms of neurodegeneration are largely unexplored. The most successful animal model for DS is the Ts65Dn mouse, but several new models have also been developed. In the current review, we discuss recent findings and potential treatment options for the management of memory loss and AD neuropathology in DS mouse models. We also review age-related neuropathology, and recent findings from neuroimaging studies. The validation of appropriate DS mouse models that mimic neurodegeneration and memory loss in humans with DS can be valuable in the study of novel preventative and treatment interventions, and may be helpful in pinpointing gene-gene interactions as well as specific gene segments involved in neurodegeneration.

show abstract

Donepezil Significantly Improves Abilities in Daily Lives of Female down Syndrome Patients with Severe Cognitive Impairment: A 24-Week Randomized, Double-Blind, Placebo-Controlled Trial

Abstract: Donepezil may effectively and safely improve overall functioning of DS patients with severe cognitive impairment.

Cited by 45 publications

References 14 publications

Florbetapir PET, FDG PET, and MRI in Down syndrome individuals with and without Alzheimer's dementia

Florbetapir PET, FDG PET, and MRI in Down syndrome individuals with and without Alzheimer's dementia

Acute neuropsychiatric disorders in adolescents and young adults with Down syndrome: Japanese case reports

Cognitive Impairment, Neuroimaging, and Alzheimer Neuropathology in Mouse Models of Down Syndrome

Contact Info

Product

Resources

About