Treatment Of Mild Cognitive Impairment Research Articles

Possible role of nicotine for the treatment of mild cognitive impairment

Evaluation of: Newhouse P, Kellar K, Aisen P et al. Nicotine treatment of mild cognitive impairment: a 6-month double-blind pilot clinical trial. Neurology 78(2), 91–101 (2012).There have been several drug trials in recent years investigating the efficacy of commonly used Alzheimer’s disease therapies for symptoms of mild cognitive impairment (MCI). However, there are no US FDA-approved pharmacological treatments for MCI. As the incidence rates of MCI are considerable, it is clear that better treatments for MCI need to be developed. The reviewed paper presents new data on a pilot clinical trial which shows that transdermal nicotine treatment for 6 months improved cognitive performance in subjects with amnestic MCI. Further studies will possibly bring us wider usage of nicotine for individuals with cognitive dysfunction.

Nicotine treatment of mild cognitive impairment

To preliminarily assess the safety and efficacy of transdermal nicotine therapy on cognitive performance and clinical status in subjects with mild cognitive impairment (MCI). Nonsmoking subjects with amnestic MCI were randomized to transdermal nicotine (15 mg per day or placebo) for 6 months. Primary outcome variables were attentional improvement assessed with Connors Continuous Performance Test (CPT), clinical improvement as measured by clinical global impression, and safety measures. Secondary measures included computerized cognitive testing and patient and observer ratings. Of 74 subjects enrolled, 39 were randomized to nicotine and 35 to placebo. 67 subjects completed (34 nicotine, 33 placebo). The primary cognitive outcome measure (CPT) showed a significant nicotine-induced improvement. There was no statistically significant effect on clinician-rated global improvement. The secondary outcome measures showed significant nicotine-associated improvements in attention, memory, and psychomotor speed, and improvements were seen in patient/informant ratings of cognitive impairment. Safety and tolerability for transdermal nicotine were excellent. This study demonstrated that transdermal nicotine can be safely administered to nonsmoking subjects with MCI over 6 months with improvement in primary and secondary cognitive measures of attention, memory, and mental processing, but not in ratings of clinician-rated global impression. We conclude that this initial study provides evidence for nicotine-induced cognitive improvement in subjects with MCI; however, whether these effects are clinically important will require larger studies. This study provides Class I evidence that 6 months of transdermal nicotine (15 mg/day) improves cognitive test performance, but not clinical global impression of change, in nonsmoking subjects with amnestic MCI.

Proteomic analysis of brain proteins in APP/PS‐1 human double mutant knock‐in mice with increasing amyloid β‐peptide deposition: Insights into the effects of in vivo treatment with N‐acetylcysteine as a potential therapeutic intervention in mild cognitive impairment and Alzheimer's disease

Proteomics analyses were performed on the brains of wild-type (WT) controls and an Alzheimer's disease (AD) mouse model, APP/PS-1 human double mutant knock-in mice. Mice were given either drinking water or water supplemented with N-acetylcysteine (NAC) (2 mg/kg body weight) for a period of five months. The time periods of treatment correspond to ages prior to Aβ deposition (i.e. 4-9 months), resembling human mild cognitive impairment (MCI), and after Aβ deposition (i.e. 7-12 months), more closely resembling advancing stages of AD. Substantial differences exist between the proteomes of WT and APP/PS-1 mice at 9 or 12 months, indicating that Aβ deposition and oxidative stress lead to downstream changes in protein expression. Altered proteins are involved in energy-related pathways, excitotoxicity, cell cycle signaling, synaptic abnormalities, and cellular defense and structure. Overall, the proteomic results support the notion that NAC may be beneficial for increasing cellular stress responses in WT mice and for influencing the levels of energy- and mitochondria-related proteins in APP/PS-1 mice.

P.5.e.001 Efficacy and safety of galantamine in long-term treatment for mild cognitive impairment

P.5.e.001 Efficacy and safety of galantamine in long-term treatment for mild cognitive impairment

Cognitive and clinical outcomes of homocysteine‐lowering B‐vitamin treatment in mild cognitive impairment: a randomized controlled trial

Homocysteine is a risk factor for Alzheimer's disease. In the first report on the VITACOG trial, we showed that homocysteine-lowering treatment with B vitamins slows the rate of brain atrophy in mild cognitive impairment (MCI). Here we report the effect of B vitamins on cognitive and clinical decline (secondary outcomes) in the same study. This was a double-blind, single-centre study, which included participants with MCI, aged ≥ 70 y, randomly assigned to receive a daily dose of 0.8 mg folic acid, 0.5 mg vitamin B(12) and 20 mg vitamin B(6) (133 participants) or placebo (133 participants) for 2 y. Changes in cognitive or clinical function were analysed by generalized linear models or mixed-effects models. The mean plasma total homocysteine was 30% lower in those treated with B vitamins relative to placebo. B vitamins stabilized executive function (CLOX) relative to placebo (P = 0.015). There was significant benefit of B-vitamin treatment among participants with baseline homocysteine above the median (11.3 µmol/L) in global cognition (Mini Mental State Examination, P < 0.001), episodic memory (Hopkins Verbal Learning Test-delayed recall, P = 0.001) and semantic memory (category fluency, P = 0.037). Clinical benefit occurred in the B-vitamin group for those in the upper quartile of homocysteine at baseline in global clinical dementia rating score (P = 0.02) and IQCODE score (P = 0.01). In this small intervention trial, B vitamins appear to slow cognitive and clinical decline in people with MCI, in particular in those with elevated homocysteine. Further trials are needed to see if this treatment will slow or prevent conversion from MCI to dementia.

P4‐394: Caregiver burden decreases in women following behavioral intervention for mild cognitive impairment

P4‐394: Caregiver burden decreases in women following behavioral intervention for mild cognitive impairment

P03-127 - Galantamine in long-term treatment formild cognitive impairment: Efficacy and safety

IntroductionTo evaluate the efficacy of galantamine in patients with Mild Cognitive Impairment. So there is a possible benefit in the deficit in executive and cognitive cerebral function (cholinergic system) with treatment with Galantamine.PurposeGalantamine is a reversible, competitive cholinesterasa inhibitor that also allosterically modulates nicotine acetylcholine receptors. Inhibition of acetylcholinesterase, the enzyme responsible for hydrolisis of acetylcholine at the cholinergic cognitive impairment. To evaluate the efficacy, safety and tolerability of galantamine in long-term in Mild Cognitive Disorder.MethodsA multicenter, open label, prospective, observational study enrolled 1028 patients, more 55 years old with Mild Neurocognitive Disorder (DSM IV criteria), during 30 months of treatment with galantamine 16 mg./day. Assessments included the MMSE, CDR, ADAS-GOG, FAQ, GCI, Trail making test, Global Deterioration Scale, and UKU scale of Adverse Effects.ResultsA total 1028 outpatients were treated with 16 mg./day galantamine during 30 months, the therapeutic response evaluated with CDR, MMSE and the tests and scales of function cognitive measuring, GCI and UKU scale of adverse effects, comparing the baseline to final scores.ConclusionMild Cognitive Disorder is being examined, so there aren’t enought treatment for this. A long-term treatment (30 months) galantamine improves cognition and global function, behavioural symptoms and the general state well being of patients with MCD. With incidence of adverse effects not significant and a very good profile of safety, the final results of the study suggest that galantamine may be particularly appropiate in the Mild Cognitive Disorder.

Guidelines for dementia and cognitive impairment in China: the diagnosis and treatment of mild cognitive impairment

近年来,关于轻度认知障碍(mild cognitive impairment,MCI)的概念、标准、诊断和治疗方面相关研究不断进展,为指南制定提供了依据.本指南旨在结合临床实践,对MCI的临床分型、诊断流程、预防和治疗等方面进行推荐。

A review of the effectiveness of memory interventions in mild cognitive impairment (MCI)

Mild cognitive impairment (MCI) is commonly associated with memory impairment. There have been a number of studies attempting to ameliorate this through memory interventions including memory rehabilitation and training. The current paper reviews the evidence for the effectiveness of such interventions in enhancing learning of specific information, their impact on untrained material, compensation for memory impairment and improving everyday functioning. The literature was systematically searched for studies focusing on interventions targeting memory impairment in MCI using relevant search terms. Studies were screened for inclusion or exclusion using a priori criteria and, once identified, studies were examined for quality using pre-specified criteria. A total of 226 studies were identified in the search, ten of which were included in the final review. Only one study was an RCT of "adequate" methodology. It was tentatively suggested that people with MCI can learn specific information, although there was little evidence to suggest that memory training can generalize. There was some limited evidence of ability to learn to compensate for memory difficulties and contradictory findings regarding improvement in everyday life. The poor methodological quality of the included studies implies that the ability to draw conclusions is limited. MCI is a controversial concept and there is a need for good quality trials examining the efficacy of memory interventions. There are some indications that memory impairment in MCI might best be targeted by interventions developing compensatory strategies and targeting the learning of specific information relevant to the individual.

Cognitive training intervention in mild cognitive impairment: A randomized, prospective, controlled, single-blinded trial

Cognitive training intervention in mild cognitive impairment: A randomized, prospective, controlled, single-blinded trial

P01-363 - Drug treatment of mild cognitive impairment

IntroductionDementia is an acquired syndrome of organic nature, characterized by permanent impairment of memory and other intellectual functions, often associated with psychological and behavioral symptoms without impairment of consciousness. There are psychopathological manifestations.There are different subtypes of dementia. To determine a mild cognitive impairment, the average score of Minimental scale test must be between 21 and 26.Clinical evidenceIt has been shown that patients with cognitive impairment have a decreased activity of acetylcholine and increased activity of glutamate. Therefore there is a decline in cognitive ability with significant memory impairment and increased aurousal. There is an impairment of cognitive function to perceive, process and use information, which contributes, along with the intelligence, plan and solve problems, learn from the experience, plan tasks and predict results.HypothesisFor this postulate two fundamental ways in the treatment by use of cholinesterase inhibitors using memantine that blocks NMDA receptors.ConclusionsHowever in mild cognitive impairment there is no evidence that these treatments improve patient outcome. Therefore we start treatment with cholinesterase inhibitors when Minimental score between 14 and 24. We'll use cholinesterase inhibitors in combination with memantine when the Minimental score between 10 and 14. We will use only memantine when the score between 3-14. It has been shown that only 30% of mild cognitive impairment progress to dementia. It is important to consider the use of these treatments because it is'nt shown a clear benefit in mild cognitive impairment and have side effects.

DONEPEZIL TREATMENT OF PATIENTS WITH MCI: A 48-WEEK RANDOMIZED, PLACEBO- CONTROLLED TRIAL

Treatment of mild cognitive impairment (MCI) with cholinesterase inhibitors may improve symptoms.In this multicenter, randomized, placebo-controlled trial, subjects with MCI entered a 3-week placebo run-in period followed by 48 weeks of double-blind donepezil (5 mg/day for 6 weeks, then 10 mg/day for 42 weeks) or placebo treatment. Primary efficacy variables included change from baseline in the modified Alzheimer Disease Assessment Scale-cognitive subscale (ADAS-Cog) and Clinical Dementia Rating Scale-sum of boxes (CDR-SB) after 48 weeks of treatment (modified intention-to-treat analysis). Secondary efficacy measures evaluated cognition, behavior, and function.The dual primary efficacy endpoint was not reached. We noted a small, but significant, decrease in modified ADAS-Cog scores in favor of donepezil at study endpoint. Little change from baseline in CDR-SB and secondary variables was observed for either group. Patient Global Assessment scores favored donepezil at all time points except week 12 (p < or = 0.05). Perceived Deficits Questionnaire scores favored donepezil at week 24 (p = 0.05). Clinical Global Impression of Change-MCI scores favored donepezil only at week 6 (p = 0.04). Adverse events were generally mild or moderate. More donepezil-treated subjects (18.4%) discontinued treatment due to adverse events than placebo-treated subjects (8.3%).Donepezil demonstrated small but significant improvement on the primary measure of cognition but there was no change on the primary measure of global function. Most other measures of global impairment, cognition, and function were not improved, possibly because these measures are insensitive to change in MCI. Responses on subjective measures suggest subjects perceived benefits with donepezil treatment.

Treatment of Mild Cognitive Impairment (MCI)

Mild cognitive impairment (MCI), an intermediate stage between normalcy and dementia, is characterized by fewer symptoms and less functional decline than dementia with less established biological disease processes and is an attractive target for both symptomatic and disease progression therapies. It is always desirable to treat symptoms or slow disease at a stage where the individual is still largely functional. Therapeutic studies in MCI have either been symptomatic, usually of shorter duration or of longer multiyear terms to demonstrate whether disease progression is delayed. Symptomatic agents tested to date include donepezil, SGS-742, and Piracetam. No symptomatic drug study has demonstrated clinically convincing differences between placebo and the study medication. Disease progression trials in MCI investigations of 2 to 4 year durations have included donepezil, vitamin E, rivastigmine, galantamine and rofecoxib. None have demonstrated convincing effects in delaying longer term disease progression or conversion to dementia. Problems that may have undermined these trials; i) disease heterogeneity, ii) slow early progression of the disease, and iii) insensitive cognitive and functional instruments. Future MCI studies may benefit from the use of biomarkers such as apolipoprotein E (APOE4), cerebrospinal fluid amyloid-beta1-42 and Tau levels and PIB positivity on brain PET scans as well as more sensitive neuropsychological test measures may also more accurately reflect clinical changes related to drug effects.

Health economic effect of donepezil treatment for CDR 0.5 converters to Alzheimer's disease as shown by the Markov model

The previous health economic simulation of donepezil based on the Markov model revealed the treatment for mild to moderate stage of Alzheimer disease (AD) to be cost-effective. Our aim was to examine the economic effect of donepezil treatment for mild cognitive impairment, from which about 15% convert to dementia per year. We constructed a new Markov model using three simulations. Namely, Simulation A hypothesized that mild AD patients, i.e., Clinical Dementia Rating (CDR) 1, received donepezil as in the previous study. Simulation B hypothesized that all CDR 0.5 subjects received donepezil, and Simulation C considered that only the CDR 0.5 converters to dementia received donepezil. We calculated the models as follows: Simulation B, supposes that the annual transition probabilities were reduced even from 15% to 10% by donepezil, however, the drug had a negative economic effect. By contrast, in Simulation C, the annual transition probability was reduced from only 15% to 12% by donepezil, there was a positive economic effect. Since it is necessary to reduce the annual transition probability from 15% to 12% in order to manifest a concomitant economic benefit, we consider that early detection of CDR 0.5 converters in the community is important for health policy planning.

Early intervention for mild cognitive impairment: a randomised controlled trial

Background:Positive effects are reported for memory training for healthy older adults, and yet there is limited information about the benefit of cognitive intervention for older adults with increasing memory difficulties—mild...

Donepezil treatment of patients with MCI

Treatment of mild cognitive impairment (MCI) with cholinesterase inhibitors may improve symptoms. In this multicenter, randomized, placebo-controlled trial, subjects with MCI entered a 3-week placebo run-in period followed by 48 weeks of double-blind donepezil (5 mg/day for 6 weeks, then 10 mg/day for 42 weeks) or placebo treatment. Primary efficacy variables included change from baseline in the modified Alzheimer Disease Assessment Scale-cognitive subscale (ADAS-Cog) and Clinical Dementia Rating Scale-sum of boxes (CDR-SB) after 48 weeks of treatment (modified intention-to-treat analysis). Secondary efficacy measures evaluated cognition, behavior, and function. The dual primary efficacy endpoint was not reached. We noted a small, but significant, decrease in modified ADAS-Cog scores in favor of donepezil at study endpoint. Little change from baseline in CDR-SB and secondary variables was observed for either group. Patient Global Assessment scores favored donepezil at all time points except week 12 (p < or = 0.05). Perceived Deficits Questionnaire scores favored donepezil at week 24 (p = 0.05). Clinical Global Impression of Change-MCI scores favored donepezil only at week 6 (p = 0.04). Adverse events were generally mild or moderate. More donepezil-treated subjects (18.4%) discontinued treatment due to adverse events than placebo-treated subjects (8.3%). Donepezil demonstrated small but significant improvement on the primary measure of cognition but there was no change on the primary measure of global function. Most other measures of global impairment, cognition, and function were not improved, possibly because these measures are insensitive to change in MCI. Responses on subjective measures suggest subjects perceived benefits with donepezil treatment.

The prevention and treatment of cognitive decline and dementia: An overview of recent research on experimental treatments

The prevention and treatment of cognitive impairment in the elderly has assumed increasing importance in an aging population. This article presents a qualitative review of recent research on experimental interventions for the prevention and treatment of mild cognitive impairment and Alzheimer's disease in elderly subjects. Interventions addressed range from lifestyle measures to pharmacological treatments. Epidemiological studies suggest that dietary measures, physical exercise, and mental activity may reduce the risk of cognitive impairment and Alzheimer's disease in elderly subjects. Statins may protect against incident dementia, and lithium may convey similar benefits to bipolar patients. Ginkgo appears ineffective as a primary preventive measure. Donepezil but not Vitamin E may benefit persons with mild cognitive impairment. Experimental treatments potentially useful for Alzheimer's disease include dimebon, PBT2 and etanercept; the safety and efficacy of the Alzheimer's vaccine remains to be proven, and growth hormone secretagogue and tarenflurbil are likely ineffective. Herbal treatments merit study in elderly subjects with cognitive syndromes.

Diagnosis and Treatment of Dementia: 3. Mild Cognitive Impairment and Cognitive Impairment Without Dementia

Background:Mild cognitive impairment and cognitive impairment, no dementia, are emerging terms that encompass the clinical state between normal cognition and dementia in elderly people. Controversy surrounds their characterization, definition and application in clinical practice. In this article, we provide physicians with practical guidance on the definition, diagnosis and treatment of mild cognitive impairment and cognitive impairment, no dementia, based on recommendations from the Third Canadian Consensus Conference on the Diagnosis and Treatment of Dementia, held in March 2006. Methods: We developed evidence-based guidelines using systematic literature searches, with specific criteria for study selection and quality assessment, and a clear and transparent decision-making process. We selected studies published from January 1996 to December 2005 that had mild cognitive impairment or cognitive impairment, no dementia, as the outcome. Subsequent to the conference, we searched for additional articles publi...

Cholinesterase inhibitors are not beneficial in the treatment of mild cognitive impairment

Cholinesterase inhibitors are not beneficial in the treatment of mild cognitive impairment

Key lessons learned from short-term treatment trials of cholinesterase inhibitors for amnestic MCI

This paper reviews the key lessons learned from the first published short-term, placebo-controlled trial of a cholinesterase inhibitor for treatment of mild cognitive impairment (MCI). The study was a 24-week placebo-controlled trial designed to evaluate the efficacy and safety of donepezil HCl (donepezil) in the treatment of cognitive impairment in subjects with MCI. Primary outcome measures were the NYU Paragraphs Test and the ADCS Clinicians Global-Impression of Change in the intent-to-treat last-observation-carried-forward group. There was no benefit of donepezil treatment on primary outcome measures (NYU Paragraphs and ADCS CGI-C) in the ITT-LOCF group but positive findings were seen on NYU Paragraphs in the fully evaluable group and in certain secondary outcome measures across both groups. The results highlight the need for the use of primary cognitive and functional measures that are reliable and sensitive to change in patients with MCI. Measures of episodic memory, psychomotor speed and complex attention were most sensitive in this study. Functional rating scales are needed that measure change in individual subjects' key areas of functional deficit, which typically involve executive aspects of instrumental ADLs. Tolerability can be increased by use of flexible dosing and efficacy is likely to be enhanced by increasing the length of the trial from six to 12 months and by enriching the sample with subjects more likely to decline during the trial.