20 research outputs found
Cholinesterase inhibitors do not alter the length of stay in nursing homes among patients with Alzheimer’s disease: a prospective, observational study of factors affecting survival time from admission to death
Functional response to cholinesterase inhibitor therapy in a naturalistic Alzheimer’s disease cohort
Economic evaluation of cholinesterase inhibitor therapy for dementia: comparison of Alzheimer's disease and Dementia with Lewy bodies.
OBJECTIVE: To assess the cost effectiveness of cholinesterase inhibitor (ChEI) treatment in patients with Alzheimer's disease (AD) and Dementia with Lewy bodies (DLB). METHOD: We used 4-month open label follow-up data from routine memory clinic patients. There were 852 patients with AD and 112 with DLB. We applied three predictive models to estimate clinical and economic outcomes at five years, comparing AD and DLB patients with hypothetical untreated controls. RESULTS: The mean improvement in MMSE in 852 AD patients was 0.57 (SD 3.4) at 4 months, and in the subgroup with baseline MMSE of 10-20 (moderate) was 1.6 (SD 3.7). Overall, the 112 DLB patients improved by 1.4 (SD 3.7). DLB patients with an MMSE 10-20 improved by 3.1 (SD 4.5) points. These efficacy data were input into the SHTAC, microsimulation and Markov models and produced estimated costs per QALY gained (CQG) for all AD of pound194,066, pound67,904 and pound123,935 respectively. In comparison, the CQGs for all DLB were pound46,794, pound2,706 and pound35,922. For the moderate subgroups only the SHTAC and microsimulation models were applicable. These gave CQG estimates for moderate AD of pound39,664 and cost saving respectively. For moderate DLB, both estimates were cost saving. CONCLUSION: The cost per QALY gained of cholinesterase treatment of all patients with DLB (including those with MMSE outside the 10-20 range) is comparable to that of patients with moderate AD, and is probably cost saving
Economic evaluation of cholinesterase inhibitor therapy for dementia: comparison of Alzheimer's disease and Dementia with Lewy bodies.
OBJECTIVE: To assess the cost effectiveness of cholinesterase inhibitor (ChEI) treatment in patients with Alzheimer's disease (AD) and Dementia with Lewy bodies (DLB). METHOD: We used 4-month open label follow-up data from routine memory clinic patients. There were 852 patients with AD and 112 with DLB. We applied three predictive models to estimate clinical and economic outcomes at five years, comparing AD and DLB patients with hypothetical untreated controls. RESULTS: The mean improvement in MMSE in 852 AD patients was 0.57 (SD 3.4) at 4 months, and in the subgroup with baseline MMSE of 10-20 (moderate) was 1.6 (SD 3.7). Overall, the 112 DLB patients improved by 1.4 (SD 3.7). DLB patients with an MMSE 10-20 improved by 3.1 (SD 4.5) points. These efficacy data were input into the SHTAC, microsimulation and Markov models and produced estimated costs per QALY gained (CQG) for all AD of pound194,066, pound67,904 and pound123,935 respectively. In comparison, the CQGs for all DLB were pound46,794, pound2,706 and pound35,922. For the moderate subgroups only the SHTAC and microsimulation models were applicable. These gave CQG estimates for moderate AD of pound39,664 and cost saving respectively. For moderate DLB, both estimates were cost saving. CONCLUSION: The cost per QALY gained of cholinesterase treatment of all patients with DLB (including those with MMSE outside the 10-20 range) is comparable to that of patients with moderate AD, and is probably cost saving
Effectiveness of acetylcholinesterase inhibitors: diagnosis and severity as predictors of response in routine practice.
BACKGROUND: Evidence from open label studies has indicated that patients with dementia with Lewy bodies (DLB) and Parkinson's disease dementia (PDD) do better than those with other diagnoses, including Alzheimer's disease (AD). In addition, those with dementia of moderate severity do better than those with mild severity. METHOD: Data collected for the monitoring of cholinesterase inhibitor prescribing in Oxfordshire over four years were supplemented with retrospective case notes inspection. 'Clinical response' was defined as improvement sufficient to merit continuation of therapy. A mini-mental state examination (MMSE) improvement of 2 or more points was defined as a 'cognitive response'. RESULTS: Medication was prescribed for 1322 patients and outcome data was available on 1250. Subsequently, 939 patients were reassessed after a mean of 120 days (SD 64.1). Medication was discontinued early by 311, mainly due to side effects. Of those who reached reassessment, 82% (771 of 939) were clinical responders and 37% (232 of 622) were cognitive responders. Overall, MMSE scores improved by +0.6 points [95% Confidence Intervals (CI) 0.3-0.9] and by +1.0 points (95% CI 0.7-1.3) in clinical responders; and deteriorated -1.5 points (95% CI -0.9--2.1) in clinical non-responders. A greater probability of clinical response was seen for DLB/PDD compared to AD patients (Odds Ratio (OR) = 2.28, 95% CI 1.07-4.89], and in men (OR = 1.51, 95% CI 1.02-2.23). A positive cognitive response was predicted by DLB/PDD compared to AD (OR = 2.07, 95% CI 1.16-3.70), moderate dementia compared to mild dementia (OR = 3.90, 95% CI 2.75-5.52), and by increasing age (OR 1.03 for each incremental year, 95% CI 1.01-1.06). Those with moderate dementia were not more likely to have a positive clinical response than those with mild dementia. CONCLUSIONS: DLB/PDD patients were more likely to be both clinical and cognitive responders than those with AD. The finding that cognitive, but not clinical, response was more likely in those with moderate dementia than in those with mild dementia accords with the findings from randomised studies in the January 2006 revision of the NICE Appraisal Consultation Document
Predicting response to acetylcholinesterase inhibitor treatment in Alzheimer disease: has the time come?
An Investigation of Levetiracetam in Alzheimer's Disease (ILiAD): a double-blind, placebo-controlled, randomised crossover proof of concept study.
BACKGROUND: Although Alzheimer's disease affects around 800,000 people in the UK and costs almost £23 billion per year, currently licenced treatments only offer modest benefit at best. Seizures, which are more common in patients with Alzheimer's disease than age matched controls, may contribute to the loss of nerve cells and abnormal brain discharges can disrupt cognition. This aberrant electrical activity may therefore present potentially important drug targets. The anti-seizure medication levetiracetam can reduce abnormal cortical discharges and reverse memory deficits in a mouse model of Alzheimer's disease. Levetiracetam has also been shown to improve memory difficulties in patients with mild cognitive impairment, a precursor to Alzheimer's disease. Clinical use of levetiracetam is well-established in treatment of epilepsy and extensive safety data are available. Levetiracetam thus has the potential to provide safe and efficacious treatment to help with memory difficulties in Alzheimer's disease. METHODS: The proposed project is a proof of concept study to test whether levetiracetam can help cognitive function in people with dementia. We plan to recruit thirty patients with mild to moderate Alzheimer's disease with no history of previous seizures or other significant co-morbidity. Participants will be allocated to a double-blind placebo-controlled crossover trial that tests levetiracetam against placebo. Standardised scales to assess cognition and a computer-based touchscreen test that we have developed to better detect subtle improvements in hippocampal function will be used to measure changes in memory. All participants will have an electroencephalogram (EEG) at baseline. The primary outcome measure is a change in the computer-based touchscreen cognitive task while secondary outcomes include the effect of levetiracetam on mood, quality of life and modelling of the EEG, including time series measures and feature-based analysis to see whether the effect of levetiracetam can be predicted. The effect of levetiracetam and placebo will be compared within a given patient using the paired t-test and the analysis of covariance adjusting for baseline values. DISCUSSION: This is the first study to evaluate if an anti-seizure medication can offer meaningful benefit to patients with Alzheimer's disease. If this study demonstrates at least stabilisation of memory function and/or good tolerability, the next step will be to rapidly progress to a larger study to establish whether levetiracetam may be a useful and cost-effective treatment for patients with Alzheimer's disease. TRIAL REGISTRATION: ClinicalTrials.gov NCT03489044 . Registered on April 5, 2018
An investigation of levetiracetam in Alzheimer's disease (ILiAD): a double-blind, placebo-controlled, randomised crossover proof of concept study
Background
Although Alzheimer’s disease affects around 800,000 people in the UK and costs almost £23 billion per year, currently licenced treatments only offer modest benefit at best. Seizures, which are more common in patients with Alzheimer’s disease than age matched controls, may contribute to the loss of nerve cells and abnormal brain discharges can disrupt cognition. This aberrant electrical activity may therefore present potentially important drug targets. The anti-seizure medication levetiracetam can reduce abnormal cortical discharges and reverse memory deficits in a mouse model of Alzheimer’s disease. Levetiracetam has also been shown to improve memory difficulties in patients with mild cognitive impairment, a precursor to Alzheimer’s disease. Clinical use of levetiracetam is well-established in treatment of epilepsy and extensive safety data are available. Levetiracetam thus has the potential to provide safe and efficacious treatment to help with memory difficulties in Alzheimer’s disease.
Methods
The proposed project is a proof of concept study to test whether levetiracetam can help cognitive function in people with dementia. We plan to recruit thirty patients with mild to moderate Alzheimer’s disease with no history of previous seizures or other significant co-morbidity. Participants will be allocated to a double-blind placebo-controlled crossover trial that tests levetiracetam against placebo. Standardised scales to assess cognition and a computer-based touchscreen test that we have developed to better detect subtle improvements in hippocampal function will be used to measure changes in memory. All participants will have an electroencephalogram (EEG) at baseline. The primary outcome measure is a change in the computer-based touchscreen cognitive task while secondary outcomes include the effect of levetiracetam on mood, quality of life and modelling of the EEG, including time series measures and feature-based analysis to see whether the effect of levetiracetam can be predicted. The effect of levetiracetam and placebo will be compared within a given patient using the paired t-test and the analysis of covariance adjusting for baseline values.
Discussion
This is the first study to evaluate if an anti-seizure medication can offer meaningful benefit to patients with Alzheimer’s disease. If this study demonstrates at least stabilisation of memory function and/or good tolerability, the next step will be to rapidly progress to a larger study to establish whether levetiracetam may be a useful and cost-effective treatment for patients with Alzheimer’s disease.
Trial registration
ClinicalTrials.govNCT03489044. Registered on April 5, 2018