The role of nutrients in the prevention and treatment of Alzheimer's disease: methodology for a systematic review.

There is a large body of existing data on nutrition in Alzheimer's disease (AD). We are conducting a systematic review of published scientific literature to determine the role of specific nutrients, both individually and in combination, in the prevention and treatment of AD. This will contribute towards a structured evidence base to help inform the clinical management of AD. The objective of the systematic review is to evaluate the strength of evidence from both observational cohort studies and randomized controlled trials on the role of fats, vitamins, antioxidants and other nutrients in the prevention and treatment of AD. We present here the methodology of our systematic review.

Speaking of research advance directives: planning for future research participation.

OBJECTIVE: To examine one model of research advance directive as a possible way to reduce the mismatch between patient and proxy choices and also to learn more about how patients with mild to moderate dementia may want to keep decision making or cede it to their proxies in the future. METHODS: Separate interviews were conducted with 149 dyads of dementia patients and family proxies about future enrollment in five types of research. Subsequent joint interviews were conducted with 69 of those dyads to discuss their separately articulated decisions and ask whether the patient prefers future enrollment decisions to be made as he or she directs today or as the proxy deems best in the future. RESULTS: Patients chose to cede future decision making to their proxies in 82.9% of the trials. Patients ceded decisions to their proxies in 80.7% of those trials about which the dyad had given opposite answers (n = 74, 49.7%). Patients who had expressed discomfort about the prospect of the proxy making an enrollment decision in a trial (n = 49, 32.9%) ceded decision making to their proxies in 45.7% of those trials. CONCLUSIONS: Both patients and proxies were willing to discuss future research enrollment in the context of an advance directive for research. Such a document may be helpful to proxies and researchers in the future to judge the types of research and associated risks patients are willing to enroll in. Although most patients willingly cede future decisions to their proxies, a sizeable minority do not wish to do so.

Twenty-four-hour rhythms of sleep-wake cycle and temperature in Alzheimer's disease.

The authors aimed to examine the difference in 24-hour rhythms of sleep-wake cycle and temperature between Alzheimer's disease (AD) patients and elderly comparison subjects. The continuous measuring of wrist activity and skin temperature was conducted for 96 hours in seven AD patients (age: 77.0 +/- 4.3) and 11 normal comparison subjects (age: 74.2 +/-5.2). The mean acrophases and amplitudes of the two rhythms in the AD group were not different from those in the comparison group. The mean phase difference between the two rhythms, however, was significantly lower in the AD group than in the comparison group.

Vinpocetine for cognitive impairment and dementia.

BACKGROUND: Vinpocetine is a synthetic ethyl ester of apovincamine, a vinca alkaloid obtained from the leaves of the Lesser Periwinkle (Vinca minor) and discovered in the late 1960s. Although used in human treatment for over twenty years, it has not been approved by any regulatory body for the treatment of cognitive impairment. Basic sciences studies have been used to claim a variety of potentially important effects in the brain. However, despite these many proposed mechanisms and targets, the relevance of this basic science to clinical studies is unclear. OBJECTIVES: To assess the efficacy and safety of vinpocetine in the treatment of patients with cognitive impairment due to vascular disease, Alzheimer's disease, mixed (vascular and Alzheimer's disease) and other dementias. SEARCH STRATEGY: The Cochrane Dementia & Cognitive Improvement Group's Specialized Register was searched using the terms vinpocetin*, cavinton, kavinton, Rgh-4405, Tcv-3B, "ethyl apovincaminate", vinRx, periwinkle, "myrtle vincapervinc" and cezayirmeneksesi. The manufacturers of vinpocetine were asked for information on trials of vinpocetine for dementia. In addition we tried to collect articles not listed in MEDLINE or other sources on the Internet (e.g. articles in Hungarian and Romanian). SELECTION CRITERIA: All human, unconfounded, double-blind, randomized trials in which treatment with vinpocetine was administered for more than a day and compared to control in patients with vascular dementia, Alzheimer's dementia or mixed Alzheimer's and vascular dementia and other dementias. Non-randomized trials were excluded. DATA COLLECTION AND ANALYSIS: Data were independently extracted by the two reviewers (SzSz and PW) and cross-checked. Data from "washout" periods were not used for the analysis. For continuous or ordinal variables, such as cognitive test results, the main outcomes of interest were the change in score from baseline. The categorical outcome of global impression was transformed to binary data (improved or not improved) as was the occurrence of adverse effects; here the endpoint itself was of interest the Peto method of the "typical odds ratio" was used. A test for heterogeneity of treatment effects between the trials was made if appropriate. Data synthesis and analysis were performed using the Cochrane Review Manager software (RevMan version 4.1). MAIN RESULTS: All identified studies were performed before the 1990s and used various terms and criteria for cognitive decline and dementia. The three studies included in the review involved a total of 583 people with dementia treated with vinpocetine or placebo. The reports of these studies did not make possible any differentiation of effects for degenerative or vascular dementia. The results show benefit associated with treatment with vinpocetine 30mg/day and 60 mg/day compared with placebo, but the number of patients treated for 6 months or more was small. Only one study extended treatment to one year. Adverse effects were inconsistently reported and without regard for relationship to dose. The available data do not demonstrate many problems of adverse effects but intention-to-treat data were not available for any of the trials. REVIEWER'S CONCLUSIONS: Although the basic science is interesting, the evidence for beneficial effect of vinpocetine on patients with dementia is inconclusive and does not support clinical use. The drug seems to have few adverse effects at the doses used in the studies. Large studies evaluating the use of vinpocetine for people suffering from well defined types of cognitive impairment are needed to explore possible efficacy of this treatment.

Donepezil and flight simulator performance: effects on retention of complex skills.

We report a randomized, double-blind, parallel group, placebo-controlled study to test the effects of the acetylcholinesterase inhibitor, donepezil (5 mg/d for 30 days), on aircraft pilot performance in 18 licensed pilots with mean age of 52 years. After 30 days of treatment, the donepezil group showed greater ability to retain the capacity to perform a set of complex simulator tasks than the placebo group, p < 0.05. Donepezil appears to have beneficial effects on retention of training on complex aviation tasks in nondemented older adults.

A focus group on cognition-enhancing medications in Alzheimer disease: disparities between professionals and consumers.

The emergence of cognition-enhancing drugs in the treatment of Alzheimer disease raises questions about quality of lives for those with dementia and for their caregivers, and about the perceptions of health care professionals. This pilot study analyzes a limited data from a series of three focus groups on the experience of treatment. These groups engaged both Alzheimer disease-affected persons, their caregivers, and a multidisciplinary professional core. We conclude that therapeutic goals need to be better addressed with patients and families, as well as better monitored, with the possibility of withdrawing therapy as appropriate. We also detected, as hypothesized, considerable disparity between the perspectives of professionals and consumers regarding the benefits of therapy.

Practice parameter: management of dementia (an evidence-based review). Report of the Quality Standards Subcommittee of the American Academy of Neurology.

OBJECTIVE: To define and investigate key issues in the management of dementia and to make literature-based treatment recommendations. METHODS: The authors searched the literature for four clinical questions: 1) Does pharmacotherapy for cognitive symptoms improve outcomes in patients with dementia? 2) Does pharmacotherapy for noncognitive symptoms improve outcomes in patients with dementia? 3) Do educational interventions improve outcomes in patients and/or caregivers? 4) Do other nonpharmacologic interventions improve outcomes in patients and/or caregivers? RESULTS: Cholinesterase inhibitors benefit patients with AD (Standard), although the average benefit appears small; vitamin E likely delays the time to clinical worsening (Guideline); selegiline, other antioxidants, anti-inflammatories, and estrogen require further study. Antipsychotics are effective for agitation or psychosis in patients with dementia where environmental manipulation fails (Standard), and antidepressants are effective in depressed patients with dementia (Guideline). Educational programs should be offered to family caregivers to improve caregiver satisfaction and to delay the time to nursing home placement (Guideline). Staff of long-term care facilities should also be educated about AD to minimize the unnecessary use of antipsychotic medications (Guideline). Behavior modification, scheduled toileting, and prompted voiding reduce urinary incontinence (Standard). Functional independence can be increased by graded assistance, skills practice, and positive reinforcement (Guideline).

Harmonization of Dementia Drug Guidelines (United States and Europe): a report of the International Working Group for the Harmonization for Dementia Drug Guidelines.

The International Working Group for the Harmonization of Dementia Drug Guidelines has been active for more than 5 years attempting to improve the efficiency of international drug development. A virtual organization was formed of clinicians, scientists, industries, participants, and regulators from various nations around the world. This article summarizes a variety of conferences and physicians' papers focusing on aspects of trials ranging from diagnosis, assessment, and trial design to pharmacoeconomics and ethics.

Ethical issues in dementia.

The growing number of individuals affected by dementia will intensify the ethical issues that emerge in clinical practice and research, issues early in disease relate to genetic testing, use of medications in mildly affected persons, and diagnostic disclosure. Research issues relate to appropriate informed consent processes, conflict of interests, and research design issues, such as the use of placebos and the use of biological tissues, in the later stages of disease concern about appropriate therapeutic goals and end-of-life care is appropriate.

Clinical trials in Alzheimer disease: debate on the use of placebo controls.

During the past 10 years, there has been a rapidly growing number of pharmaceutical industry-sponsored drug trials for treatment of Alzheimer disease (AD) and other neurodegenerative diseases. As public awareness and concerns about AD have grown, so has interest in developing drug therapies for retarding symptom progression, delaying onset, and ultimately curing the disease. Ethical debate on the use of placebo control trials in AD research has come of age in the United States with the availability of treatments approved by the Food and Drug Administration. The experts and the public agree that more effective therapies are necessary, and new therapeutic options are being developed as rapidly as possible. The arguments on each side of the debate are provocative and important but do not provide unequivocal justification for either the abandonment or the maintenance of placebo-controlled trials in all AD research. Clinical trials differ with respect to scientific and practical goals, and these factors inherently affect the ethical priorities of each study. We present these contrasting points of view to delineate some of the issues rather than to make specific recommendations other than to urge that all clinical trials in AD should be designed with careful consideration of the ethical issues surrounding the use of placebo controls. As new and more effective treatments emerge, the ethical framework for placebo use in AD studies will require frequent re-examination. To make wise choices, patients, caregivers, physicians, and ethicists (among others) must have a voice in this continuing discussion.

Spirituality, religion, and Alzheimer's disease.

The chaplain's ministry to persons with dementia, often of the Alzheimer's type, is vitally relevant to their clinical well-being. No chaplain should even think that because someone is demented, they can no longer be reached spiritually. While few scientific studies exist, clinical experience and anecdotal accounts suggest that selected pastoral interventions can enhance the quality of life of the mildly, moderately, and even severely demented individual.