Alzheimer Disease: Jakimovich L

Tariot PN, Jakimovich L. · Department of Psychiatry, University of Rochester Medical Center, NY 14620, USA. · J Am Med Dir Assoc. · Pubmed #12837144 No free full text.

Abstract: The following case describes a severely demented, elderly male patient who was placed in a nursing home when he became unmanageable in an assisted-living facility. Upon admission to the nursing facility, the patient was diagnosed with relatively severe Alzheimer's disease (AD)treated with the cholinesterase inhibitor donepezil in the context of a clinical study. This report illustrates that donepezil, and perhaps by analogy other cholinesterase inhibitors as well, can be efficacious in treating the cognitive, functional, and behavioral impairment associated with advanced AD.

Profenno LA, Jakimovich L, Holt CJ, Porsteinsson A, Tariot PN. · Department of Psychiatry, University of Rochester Medical Center, NY 14620, USA. · Curr Alzheimer Res. · Pubmed #16375658 No free full text.

Abstract: OBJECTIVE: The Alzheimer's Disease Cooperative Study (ADCS) is conducting a clinical trial to address whether chronic valproate treatment can delay emergence of behavioral symptoms in outpatients with AD. Since there were no data on the safety and tolerability of divalproex sodium in outpatients with dementia, we undertook a pilot study to inform the design of the ADCS study. METHODS: We recruited 20 outpatients with probable AD, MMSE 10-20, without history of agitation or psychosis. This was a 10-week randomized, double-blind, placebo-controlled study assessing the safety and tolerability of 1,000 mg/day and 1,500 mg/day of divalproex sodium delayed-release for 8 weeks followed by extended-release for 2 weeks. Other outcome measures addressed cognition, function, global status, side effects, and laboratory data. RESULTS: Participants assigned to active treatment ingested approximately 30% less of their prescribed study medication compared to those receiving placebo (p < .05 Wilcoxon Rank Sum test). The average tolerated dose for all participants at week 8 was 810 mg/day or 11.5 mg/kg/day, similar to the dose tolerated by nursing home patients. The most common side effects were sleepiness and tiredness, with worse cognitive performance in those assigned to 1500 mg/day. CONCLUSIONS: These results were used to design the multi-center ADCS trial. Doses of less than 1000 mg/day of divalproex sodium were the maximum tolerated by these outpatients with AD. A larger study of divalproex sodium dose tolerability is needed to define treatment in outpatients with Alzheimer's disease.

Tariot PN, Raman R, Jakimovich L, Schneider L, Porsteinsson A, Thomas R, Mintzer J, Brenner R, Schafer K, Thal L, Anonymous00302, Anonymous00303. · Department of Psychiatry, The Center for Aging and Developmental Biology, Univ. of Rochester Medical Center, Rochester, NY, USA. · Am J Geriatr Psychiatry. · Pubmed #16286437 No free full text.

Abstract: OBJECTIVE: Three placebo-controlled clinical trials have suggested the benefit of valproate for treatment of agitation associated with dementia; one was used as the basis for this multicenter trial, conducted by the Alzheimer's Disease (AD) Cooperative Study. It addresses the efficacy, safety, and tolerability of divalproex sodium for the treatment of agitation associated with dementia. METHODS: This was a randomized, double-blind, placebo-controlled clinical trial in 153 nursing home residents with probable or possible AD complicated by agitation; 110 (72%) completed the trial. Participants were randomized to treatment with divalproex sodium at a target dose of 750 mg/day (N = 75) or placebo (N = 78) for 6 weeks. The primary outcome measure was change from baseline on the Brief Psychiatric Rating Scale (BPRS) Agitation factor. Secondary outcomes included total BPRS, Clinical Global Impression of Change, Cohen-Mansfield Agitation Inventory score, and measures of safety and tolerability. RESULTS: Compliance averaged 88%. Participants receiving divalproex achieved a mean dose of 800 mg/day. Change in mean BPRS Agitation factor scores did not differ between patients treated with divalproex and placebo, nor did secondary behavioral measures. Measures of safety and tolerability did not reveal clinically important drug/placebo differences. CONCLUSIONS: This multicenter trial showed no benefit of divalproex sodium for treatment for agitation in dementia at a mean dose of 800 mg/day over 6 weeks. The results do not support findings from previous trials indicating possible benefit.