Long-Term Associations between Cholinesterase Inhibitors and Memantine Use and Health Outcomes among Patients with Alzheimer's Disease

OBJECTIVES: To examine in an observational study (1) relationships between cholinesterase inhibitors (ChEI) and memantine use, and functional and cognitive end points and mortality in patients with Alzheimer's disease (AD); (2) relationships between other patient characteristics and these clinical end points; and (3) whether effects of the predictors change across time. METHODS: The authors conducted a multicenter, natural history study that included three university-based AD centers in the United States. A total of 201 patients diagnosed with probable AD with modified Mini-Mental State Examination (MMSE) scores >/= 30 at study entry were monitored annually for 6 years. Discrete-time hazard analyses were used to examine relationships between ChEI and memantine use during the previous 6 months reported at each assessment, and time to cognitive (MMSE score /= 10) end points and mortality. Analyses controlled for clinical characteristics, including baseline cognition, function, and comorbid conditions, and presence of extrapyramidal signs and psychiatric symptoms at each assessment interval. Demographic characteristics included baseline age, sex, education, and living arrangement at each assessment interval. RESULTS: ChEI use was associated with delayed time in reaching the functional end point and death. Memantine use was associated with delayed time to death. Different patient characteristics were associated with different clinical end points. CONCLUSIONS: Results suggest long-term beneficial effects of ChEI and memantine use on patient outcomes. As for all observational cohort studies, observed relationships should not be interpreted as causal effects

Dementia as a source of social disadvantage and exclusion

Objective To explore perceptions of the impacts of dementia on people living with the condition and those close to them and examine the relationship between dementia, disadvantage and social exclusion. Methods Semi-structured in-depth interviews were conducted with 111 participants: people with dementia (n = 19), carers (n = 28), health-care professionals (n = 21), social workers (n = 23) and service professionals (n = 20). NVivo 11 was used to code descriptions and identify impact areas. Results Participants described social, psychological, carer, material, service-based and disparity impacts associated with the experience of dementia. Some of these impacts correspond to social exclusion associated with age, but some are distinctive to dementia. Discussion It is argued that dementia generates its own forms of social disadvantage and exclusion. This is in addition to being subject to structural risk factors. The implications of the active effects of dementia as a social phenomenon should give rise to new policy and practice priorities.Peer reviewe

Age, gender and disability predict future disability in older people: the Rotterdam Study

<p>Abstract</p> <p>Background</p> <p>To develop a prediction model that predicts disability in community-dwelling older people. Insight in the predictors of disability is needed to target preventive strategies for people at increased risk.</p> <p>Methods</p> <p>Data were obtained from the Rotterdam Study, including subjects of 55 years and over. Subjects who had complete data for sociodemographic factors, life style variables, health conditions, disability status at baseline and complete data for disability at follow-up were included in the analysis. Disability was expressed as a Disability Index (DI) measured with the Health Assessment Questionnaire.</p> <p>We used a multivariable polytomous logistic regression to derive a basic prediction model and an extended prediction model. Finally we developed readily applicable score charts for the calculation of outcome probabilities.</p> <p>Results</p> <p>Of the 5027 subjects included, 49% had no disability, 18% had mild disability, 16% had severe disability and 18% had deceased at follow-up after six years. The strongest predictors were age and prior disability. The contribution of other predictors was relatively small. The discriminative ability of the basic model was high; the extended model did not enhance predictive ability.</p> <p>Conclusion</p> <p>As prior disability status predicts future disability status, interventive strategies should be aimed at preventing disability in the first place.</p

Genetic risk of neurodegenerative diseases is associated with mild cognitive impairment and conversion to dementia

Introduction Neurodegenerative diseases are a major cause of cognitive impairment and can ultimately lead to dementia. Genome-wide association studies have uncovered many genetic variants conferring risk of neurodegenerative diseases, but their role in cognitive impairment remains unexplored. Methods In the prospective, population-based Rotterdam Study, 3605 nondemented persons aged ≥55 years were genotyped, screened for mild cognitive impairment (MCI) in 2002 to 2005 and underwent continuous follow-up for dementia until 2012. Weighted polygenic risk scores of genetic variants for Alzheimer's disease (AD), Parkinson's disease (PD), and the frontotemporal lobar degeneration/amyotrophic lateral sclerosis disease spectrum (FTLD/ALS) were constructed and investigated for association with MCI and the subsequent conversion to dementia. Results In total, 360 (10.0%) persons had MCI, of whom 147 (4.1%) were amnestic and 213 (5.9%) nonamnestic. The AD risk score was associated with both MCI subtypes (odds ratio for all MCI 1.15 [95% CI, 1.03-1.28]), whereas PD and FTLD/ALS risk scores were associated only with nonamnestic MCI (odds ratios 1.15 [1.00-1.32] and 1.19 [1.03-1.37], respectively). The AD risk score, but not PD and FTLD/ALS risk scores, was associated with an increased risk of dementia (hazard ratio 1.55 [1.37-1.77]). Discussion Genetic evidence supports the view that multiple neurodegenerative pathways lead to MCI and that the subsequent conversion to dementia, primarily of the AD subtype, is mainly due to the AD pathway(s)

Are waiting times for hospital admissions affected by patients' choices and mobility?

Background Waiting times for elective care have been considered a serious problem in many health care systems. A topic of particular concern has been how administrative boundaries act as barriers to efficient patient flows. In Norway, a policy combining patient's choice of hospital and removal of restriction on referrals was introduced in 2001, thereby creating a nationwide competitive referral system for elective hospital treatment. The article aims to analyse if patient choice and an increased opportunity for geographical mobility has reduced waiting times for individual elective patients. Methods A survey conducted among Norwegian somatic patients in 2004 gave information about whether the choice of hospital was made by the individual patient or by others. Survey data was then merged with administrative data on which hospital that actually performed the treatment. The administrative data also gave individual waiting time for hospital admission. Demographics, socio-economic position, and medical need were controlled for to determine the effect of choice and mobility upon waiting time. Several statistical models, including one with instrument variables for choice and mobility, were run. Results Patients who had neither chosen hospital individually nor bypassed the local hospital for other reasons faced the longest waiting times. Next were patients who individually had chosen the local hospital, followed by patients who had not made an individual choice, but had bypassed the local hospital for other reasons. Patients who had made a choice to bypass the local hospitals waited on average 11 weeks less than the first group. Conclusion The analysis indicates that a policy combining increased opportunity for hospital choice with the removal of rules restricting referrals can reduce waiting times for individual elective patients. Results were robust over different model specifications

A pilot study of rivastigmine in the treatment of delirium after stroke: A safe alternative

<p>Abstract</p> <p>Background</p> <p>Delirium is a common disorder in the early phase of stroke. Given the presumed cholinergic deficiency in delirium, we tested treatment with the acetylcholinesterase inhibitor rivastigmine.</p> <p>Methods</p> <p>This pilot study was performed within an epidemiological study. In 527 consecutive stroke patients presence of delirium was assessed during the first week with the confusion assessment method. Severity was scored with the delirium rating scale (DRS). Sixty-two patients developed a delirium in the acute phase of stroke. Only patients with a severe and persistent delirium (defined as a DRS of 12 or more for more than 24 hours) were enrolled in the present study. In total 26 fulfilled these criteria of whom 17 were treated with orally administered rivastigmine with a total dose between 3 and 12 mg a day. Eight patients could not be treated because of dysphagia and one because of early discharge.</p> <p>Results</p> <p>No major side effects were recorded. In 16 patients there was a considerable decrease in severity of delirium. The mean DRS declined from 14.8 on day one to 8.5 after therapy and 5.6 after tapering. The mean duration of delirium was 6.7 days (range; 2–17).</p> <p>Conclusion</p> <p>Rivastigmine is safe in stroke patients with delirium even after rapid titration. In the majority of patients the delirium improved after treatment. A randomized controlled trial is needed to establish the usefulness of rivastigmine in delirium after stroke.</p> <p>Trial registration</p> <p>Nederlands Trial Register NTR1395</p