M. Saleem Ismail

Extended results of the Alzheimer’s disease anti-inflammatory prevention trial

Epidemiologic evidence suggests that nonsteroidal anti‐inflammatory drugs (NSAIDs) delay onset of Alzheimers dementia (AD), but randomized trials show no benefit from NSAIDs in patients with symptomatic AD. The Alzheimers Disease Anti‐inflammatory Prevention Trial (ADAPT) randomized 2528 elderly persons to naproxen or celecoxib versus placebo for 2 years (standard deviation = 11 months) before treatments were terminated. During the treatment interval, 32 cases of AD revealed increased rates in both NSAID‐assigned groups.

Chronic Divalproex Sodium to Attenuate Agitation and Clinical Progression of Alzheimer Disease

CONTEXT Agitation and psychosis are common in Alzheimer disease and cause considerable morbidity. We attempted to delay or to prevent agitation and psychosis with the use of divalproex sodium (valproate). OBJECTIVE To determine whether treatment with valproate could delay or prevent emergence of agitation or psychosis. DESIGN, SETTING, AND PATIENTS A multicenter, randomized, double-blind, placebo-controlled trial of flexible-dose valproate in 313 (of 513 screened) individuals with moderate Alzheimer disease who had not yet experienced agitation or psychosis. The study was conducted from November 1, 2005, through March 31, 2009, at 46 sites in the United States. INTERVENTION Participants were randomly assigned to valproate treatment at a target dose of 10 to 12 mg per kilogram of body weight per day or identical-appearing placebo for 24 months followed by a 2-month period of single-blind placebo treatment. MAIN OUTCOME MEASURE Time to emergence of clinically significant agitation or psychosis. RESULTS A total of 122 participants (59 receiving valproate and 63 receiving placebo) completed 24 months of treatment while taking study medication; 42 (27 receiving valproate and 15 receiving placebo) reached 24 months having discontinued study medication; 150 reached month 26. There was no difference between groups in time to emergence of agitation or psychosis (Cox proportional hazard ratio, 0.96; P = .88). There was no difference between groups in change on any secondary outcome. The valproate group had higher rates of somnolence, gait disturbance, tremor, diarrhea, and weakness. Eighty-eight participants underwent magnetic resonance imaging scans at baseline and 12 months; the valproate group showed greater loss in hippocampal and whole-brain volume, accompanied by greater ventricular expansion (P < .001). CONCLUSION Valproate treatment did not delay emergence of agitation or psychosis or slow cognitive or functional decline in patients with moderate Alzheimer disease and was associated with significant toxic effects.

National Institute of Mental Health Clinical Antipsychotic Trials of Intervention Effectiveness- Alzheimers Disease (CATIE-AD): Baseline Characteristics

CATIE-AD was a multicenter effectiveness trial of atypical antipsychotics in patients with agitation and psychosis associated with AD who resided in the community. The study enrolled 421 participants. In this paper we present and discuss baseline characteristics of participants (demographics, cognitive, behavioral, and functional assessments), caregivers (demographics and caregiver burden) and settings at randomization. Those enrolled suffered from a wide range of cognitive impairment, were medically complex and experienced acute psychopathology requiring intervention with atypical antipsychotics. Family members providing the equivalent of institutional care experienced significant depression and caregiver burden. With the increasing prevalence of AD, clinicians and health care planners should look into future needs of those AD sufferers who are residing in community.

Psychometric comparison of standard and computerized administration of the Alzheimer's Disease Assessment Scale (ADAS) among patients with mild-to-moderate Alzheimer's disease

difference between these two tests with respect to the ACE insertion/ deletion polymorphism. Chi-Square testing for trend was performed to evaluate the association ACE indel polymorphism with vascular cognitive decline; and logistic regression adjusting for the effects of age, education, gender, and ACE indel polymorphism to evaluate the factors influencing cognitive decline in post-lacunar infarct patients. Results: Among the 65 lacunar infarct patients, 23(35.4%) were women, the mean age was 64.46 6 12.35 years (26w88 years old). Twenty-two (33.8%) patients had senior high school education at least, but 10(15.4%) patients were illiterate. After ACE indel polymorphism analysis, 65 of our patients, 7(10.8%) were D/D genotype, 29(44.6%) were I/I genotype, and 29(44.6%) were I/D genotype. In our study, only fluency decline had trended to be not associated with D/D genotype (p 1⁄4 0.063) in Chi-square testing for trend. CASI (p 1⁄4 0.407) and MMSE (p1⁄4 0.997) did not show significant cognitive decline between these three genotype. After logistic regression analysis, we also did not found any significant difference between cognitive decline and ACE indel polymorphism in post-lacunar infarct patients. Conclusions: Our results can not revealed that ACE indel polymorphism is a predictor of cognitive decline in post-lacunar infarct patients. A partial explanation for this may be that the number of subjects in this study was small, and may not be able to validate the hypothesis estimate exactly. So, extent our study times to collect more patients and long term follow up our cases that may be a reasonable method to improve our results.

Galantamine in Treatment of AD

The cholinergic hypothesis proposes that well-defined deficits in cholinergic neurotransmission contribute to cognitive dysfunction in Alzheimer’s disease (AD), and that enhancing cholinergic transmission will lead to improved outcome (1). Several acetylcholinesterase inhibitors (AChEI) have been approved during the past few years on the basis of clinical trials, demonstrating that these agents improve or maintain cognitive function in patients with possible AD. Thus far all AChEI have been shown to be efficacious as a class and are considered a mainstay of AD treatment. Galantamine is the newest member of this class of agents at present.