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These results suggest that current treatments, which are relatively benign and may slow progression of disease, should be offered to patients who are identified as having AD based solely on an AAN clinical evaluation. A clinical evaluation that includes functional neuroimaging based testing will be warranted, however, when new treatments that are effective at slowing disease progression but have the potential for moderate to severe complications become available.
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Success in treating patients with progressive supranuclear palsy and corticobasal degeneration remains exceedingly low. This finding probably relates to the widespread distribution of the pathological changes that account for the varied and complex spectrum of clinical manifestations. Dopaminergic drugs are regularly used for the parkinsonian features; however, these rarely result in more than modest benefit, and when better or sustained responses are obtained, as sometimes occurs in progressive supranuclear palsy, the clinical features are atypical and diagnosis is often delayed or not made in life. A variety of other treatments have been used in both disorders, sometimes directed at other specific features such as dystonia or myoclonus, and these treatments will be reviewed. Greater success in treating these disorders will require advances in our understanding of their cause(s) or the pathogenetic mechanisms underlying the neurodegenerative processes. The similarities in the molecular pathology of these four-repeat tauopathies suggests that important advances in the management of one will have a definite impact on the treatment of the other.
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Two-hundred ninety patients were randomized to treatment in this 24-week, double-blind, placebo-controlled trial. Patients received either donepezil 5 mg/day for the first 28 days and 10 mg/day thereafter as per the clinician's judgment (n = 144) or placebo (n = 146). The primary outcome measure was the Clinician's Interview-Based Impression of Change with caregiver input (CIBIC+).
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Treatment with donepezil did not significantly improve the overall composite score, but it did result in modest improvements in several cognitive functions, especially among patients with greater pretreatment impairments.
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AchEI therapy has no unfavorable effect on nutritional status or weight in elderly patients with different types of dementia, but it seems that food intake is better in those treated by rivastigmine patch.
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One hundred and seventy-four patients fulfilled the trial. 72% were APOEomega4 carriers. No significant overall treatment effects on neuropsychiatric symptoms, on activities of daily living or on caregiver's burden were found. However, significant positive treatment effects on the scores in the NPI agitation domain in APOEomega4 carriers (p=0.006) and in MADRS scores in non-APOEomega4 carriers (p=0.005) were found.
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Series of some 3,5-dimethoxy-N-methylenebenzenamine and 4-(methyleneamino)benzoic acid derivatives comprising of N-methylenebenzenamine nucleus were designed, synthesized, characterized, and assessed for their acetylcholinesterase (AChE), butyrylcholinesterase (BChE) inhibitory, and antioxidant activity thereby improving learning and memory in rats. The IC50 values of all the compound along with standard were determined on AChE and BChE enzyme. The free radical scavenging activity was also assessed by in vitro DPPH (2,2-diphenyl-1-picryl-hydrazyl) and hydrogen peroxide radical scavenging assay. The selective inhibitions of all compounds were observed against AChE in comparison with standard donepezil. The enzyme kinetic study of the most active compound 4 indicated uncompetitive AChE inhibition. The docking studies of compound 4 exhibited the worthy interaction on active-site gorge residues Phe330 and Trp279 responsible for its high affinity towards AChE, whereas lacking of the BChE inhibition was observed due to a wider gorge binding site and absence of important aromatic amino acids interactions. The ex vivo study confirmed AChE inhibition abilities of compound 4 at brain site. Further, a considerable decrease in escape latency period of the compound was observed in comparison with standard donepezil through in vivo Spatial Reference Memory (SRM) and Spatial Working Memory (SWM) models which showed the cognition-enhancing potential of compound 4. The in vivo reduced glutathione (GSH) estimation on rat brain tissue homogenate was also performed to evaluate free radical scavenging activity substantiated the antioxidant activity in learning and memory.
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Inappropriate verbal and physical sexual behaviour is not common among individuals with dementia, but when it does occur, it can have profound consequences. We report a case of 79-year-old woman with dementia of the Alzheimer's type who complained of increased libido after an increased dose of donepezil, which was being used along with tianeptine. Donepezil withdrawal led to the resolution of increased libido, but when it was reintroduced, increased libido reappeared once again (Naranjo score: 7). Increased libido was not reported by the patient during the 6-year follow-up period after donepezil withdrawal. A potential mechanism of acetylcholinesterase inhibitor-induced increased libido and the current literature on hypersexuality as a side-effect of donepezil treatment are discussed.
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Until the results of ongoing studies are available, there is no convincing evidence to support pharmacologic intervention as an effective treatment for memory disorder in MS patients. However, donepezil, Ginkgo biloba, memantine and rivastigmine resulted to be safe and well tolerated as adverse events such as nausea, diarrhea, somnolence, and constipation were not frequent, while no serious adverse effects were reported. Future high quality randomised controlled trials are needed.
Due to the complex nature of Alzheimer's disease, there is a renewed and growing search for multitarget drugs.
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At baseline 182 were diagnosed as not depressed and not treated with SSRIs, 66 as depressed and treated with SSRIs, and 90 as depressed but not treated with SSRIs. The mean change in MMSE score from baseline to nine months showed that depressed patients not treated worsened in comparison with those not depressed and not treated with SSRIs (mean change -0.8 +/- 2.3 vs 0.04 +/- 2.9; p = 0.02) and patients depressed and treated with SSRI (mean change -0.8 +/- 2.3 vs 0.1 +/- 2.5; p = 0.03).
This study provides Class I evidence which does not support the hypothesis that 10 mg of donepezil daily for 24 weeks is superior to placebo in improving cognition as measured by the SRT in people with MS whose baseline RAVLT score was 0.5 SD or more below average.