Joan Amatniek

Incidence and Predictors of Seizures in Patients with Alzheimer's Disease

Summary:  Purpose: To determine cumulative incidence and predictors of new‐onset seizures in mild Alzheimers disease (AD) with a cohort followed prospectively. Limited information is available on the incidence of seizures, and no reports exist of seizure predictors in AD patients.

Effects of galantamine versus donepezil on sleep in patients with mild to moderate Alzheimer disease and their caregivers: a double-blind, head-to-head, randomized pilot study.

Objective:To examine the effects of galantamine and donepezil on patient and caregiver sleep. Methods:In this randomized, 8-week, double-blind, parallel-group, multicenter, pilot comparison of galantamine and donepezil, safety and efficacy data were collected. Objective and subjective changes in sleep of patients (N = 63) and their caregivers were measured. Clinicians assessed changes in patient global function. As this was a pilot study, only descriptive statistics are presented. Results:In general, neither galantamine nor donepezil, at stable doses, were associated with decrements in actigraphy sleep measurements. However, mean scores in all measures of sleep showed a tendency for minimal improvements in galantamine-treated patients and minimal decrements in the donepezil-treated patients. The same tendencies were present in caregiver sleep measures. Global function either improved or remained stable in a higher percentage of patients treated with galantamine than with donepezil. Galantamine and donepezil were both well tolerated and safe. Conclusions:This pilot study was the first to compare the effects of these drugs on sleep in patients or caregivers. Both drugs were safe and well tolerated. Neither galantamine nor donepezil negatively affected sleep; however, on every measure, there were suggestions of slightly more benefit associated with galantamine treatment. Although these results are suggestive of a differential effect of the drugs on sleep, further research is needed to confirm the clinical significance.

Scales as outcome measures for Alzheimer's disease.

The assessment of patient outcomes in clinical trials of new therapeutics for Alzheimers disease (AD) continues to evolve. In addition to assessing drugs for symptomatic relief, an increasing number of trials are focusing on potential disease‐modifying agents. Moreover, participants with AD are being studied earlier in their course of disease. As a result, the limitations of current outcome measures have become more apparent, as has the need for better instruments. In recognition of the need to review and possibly revise current assessment measures, the Alzheimers Association, in cooperation with industry leaders and academic investigators, convened a Research Roundtable meeting devoted to scales as outcome measures for AD clinical trials. The meeting included a discussion of methodological issues in the use of scales in AD clinical trials, including cross‐cultural issues. Specific topics related to the use of cognitive, functional, global, and neuropsychiatric scales were also presented. Speakers also addressed academic and industry initiatives for pooling data from untreated and placebo‐treated patients in clinical trials. A number of regulatory topics were also discussed with agency representatives. Panel discussions highlighted areas of controversy, in an effort to gain consensus on various topics.

Effects of Galantamine on Measures of Attention : Results From 2 Clinical Trials in Alzheimer Disease Patients With Comparisons to Donepezil

Deficits in attention are present early in the course of Alzheimer disease (AD). Acetylcholine receptors are appealing molecular targets for intervention as cholinergic pathways are involved in the neurobiology of attention. For this reason, measures of attention were included in 2 independent, multicenter, randomized, parallel, controlled trials in subjects with AD comparing the effects of galantamine, an acetylcholinesterase inhibitor and postulated nicotinic receptor modulator, and donepezil, an acetylcholinesterase inhibitor. The attention battery of the Cognitive Drug Research computerized assessment system was used in both trials. Small magnitude, positive signals were observed for simple and choice reaction times for both compounds. Attention task performance tended to improve early for galantamine-treated subjects. A consistent temporal pattern of improvement was not observed in donepezil-treated subjects. Quantitative findings appeared more pronounced in subjects with moderate AD. Galantamines proposed action as a nicotinic receptor modulator may bear on these findings. Improved attention may have positive effects on cognitive and functional outcomes for AD patients, although this hypothesis requires further study and validation.

Beyond In Vitro Data: A Review of In Vivo Evidence Regarding the Allosteric Potentiating Effect of Galantamine on Nicotinic Acetylcholine Receptors in Alzheimer's Neuropathology

Galantamine is an approved treatment for mild to moderate Alzheimers disease, with demonstrated benefits for cognition and functional ability in human studies. The mechanism of action that is most generally recognized as underlying the clinical benefits of galantamine is inhibition of brain acetylcholinesterase (AChE). However, an increasing body of evidence suggests that an additional mechanism, most likely allosteric modulation of nicotinic acetylcholine receptors (nAChRs), may contribute to the therapeutic effects of galantamine. This review summarizes the research on this additional mechanism, with emphasis on data derived from in vivo animal studies and open-label hypothesis-generating studies in humans. In general, these studies provide evidence of effects beyond those of AChE inhibition alone, most notably in comparisons with other AChE inhibitors, in which galantamine produced similar or greater effects at doses that provided lower levels of brain AChE inhibition. The use of nAChR agonists and antagonists in some of these studies lends support to the proposed allosteric potentiating ligand activity of galantamine at nAChRs. This dual action of galantamine may account for its therapeutic profile.

Paliperidone extended-release tablets in patients with recently diagnosed schizophrenia.

Aim: Effective early and persistent antipsychotic treatment in recently diagnosed schizophrenia may positively impact long‐term outcomes. Paliperidone extended‐release (ER) was assessed in this population.

Undertreatment of patients with Alzheimer's disease in an elderly United States population

The aim of this study was to assess the undertreatment of elderly mild to moderate Alzheimers disease (AD) patients in the United States utilizing baseline data from a community‐based trial that has established comparability to national survey samples on demographic characteristics.

One-week dose titration of extended release galantamine in patients with Alzheimer’s disease

Our purpose was to assess the safety and tolerability of extended‐release galantamine (GAL‐ER), using a 1‐week dose titration in Alzheimers patients.

Neuropsychiatric signs and symptoms of Alzheimer's disease: New treatment paradigms

Neuropsychiatric symptoms (NPSs) are hallmarks of Alzheimers disease (AD), causing substantial distress for both people with dementia and their caregivers, and contributing to early institutionalization. They are among the earliest signs and symptoms of neurocognitive disorders and incipient cognitive decline, yet are under‐recognized and often challenging to treat. With this in mind, the Alzheimers Association convened a Research Roundtable in May 2016, bringing together experts from academia, industry, and regulatory agencies to discuss the latest understanding of NPSs and review the development of therapeutics and biomarkers of NPSs in AD. This review will explore the neurobiology of NPSs in AD and specific symptoms common in AD such as psychosis, agitation, apathy, depression, and sleep disturbances. In addition, clinical trial designs for NPSs in AD and regulatory considerations will be discussed.

Neuropsychiatric signs and symptoms of Alzheimer's disease

Neuropsychiatric symptoms (NPSs) are hallmarks of Alzheimers disease (AD), causing substantial distress for both people with dementia and their caregivers, and contributing to early institutionalization. They are among the earliest signs and symptoms of neurocognitive disorders and incipient cognitive decline, yet are under‐recognized and often challenging to treat. With this in mind, the Alzheimers Association convened a Research Roundtable in May 2016, bringing together experts from academia, industry, and regulatory agencies to discuss the latest understanding of NPSs and review the development of therapeutics and biomarkers of NPSs in AD. This review will explore the neurobiology of NPSs in AD and specific symptoms common in AD such as psychosis, agitation, apathy, depression, and sleep disturbances. In addition, clinical trial designs for NPSs in AD and regulatory considerations will be discussed.