Alzheimer Disease: Porsteinsson AP

Cosman KM, Boyle LL, Porsteinsson AP. · University of Rochester School of Medicine, Alzheimer's Disease Care Research and Education Program (AD-CARE), Monroe Community Hospital, 435 East Henrietta Road, Rochester, NY 14620, USA. · Expert Opin Pharmacother. · Pubmed #17257090 No free full text.

Abstract: Memantine is the first and only medication that has been approved by European, US and Canadian regulatory agencies for the treatment of moderate-to-severe Alzheimer's disease (AD). It is an NMDA receptor antagonist that works to prevent excitotoxicity and cell death, which are mediated by the excessive influx of calcium during a sustained release of glutamate. Preclinical studies of memantine reveal that it has the potential to improve memory and learning processes after impairment has occurred, as well as to prevent further neuronal damage. Although memantine has been considered for the treatment of earlier AD, it has not yet been approved for this. Randomized controlled trials of memantine in the treatment of mild-to-moderate AD have demonstrated small treatment effects in measures of cognition, global assessment and behavior favoring the use of memantine. However, the differences between treatment groups were not consistently significant. Two ongoing long-term trials are further investigating the efficacy of memantine in the treatment of mild-to-moderate AD.

Schneider LS, Porsteinsson AP, Peskin ER, Pfeiffer EA. · No affiliation provided · Geriatrics. · Pubmed #12961833 No free full text.

This publication has no abstract.

Tariot PN, Ryan JM, Porsteinsson AP, Loy R, Schneider LS. · Department of Psychiatry, University of Rochester Medical Center and Monroe Community Hospital, Rochester, New York, USA. · Clin Geriatr Med. · Pubmed #11375140 No free full text.

Abstract: Behavioral signs and symptoms in dementia are common, morbid, classifiable, and treatable. The current state-of-the-art approach is to evaluate carefully for social or environmental causes, intercurrent medical conditions, or other triggers of the behavior and attempt to deal with those directly. When these conservative steps fail, there may be a role for medication. A rational approach typically hinges on matching the most dominant behavioral target symptoms to the most relevant medication class, the key information of which is summarized.

Porsteinsson AP, Tariot PN, Jakimovich LJ, Kowalski N, Holt C, Erb R, Cox C. · Department of Psychiatry, Program in Neurobehavioral Therapeutics, University of Rochester Medical Center and Monroe Community Hospital, tochester, NY 14620, USA. · Am J Geriatr Psychiatry. · Pubmed #12837672 No free full text.

Abstract: OBJECTIVE: The authors describe an open-label extension of a double-blind, randomized, placebo-controlled study of divalproex sodium in 56 nursing home patients with agitation and dementia. METHODS: Participants (N=46) were treated for 6 weeks in an open fashion with clinically optimal doses of divalproex sodium (range: 250 mg/day-1,500 mg/day; mean: 851 mg/day). Behavior was assessed with the Brief Psychiatric Rating Scale (BPRS) and Clinical Global Impression of Change (CGI) by new raters. Safety, tolerability, and laboratory data were obtained regularly. RESULTS: The mean BPRS Agitation Factor decreased by 3.1 points from baseline; 86% of those completing the open phase were rated as improved on the CGI. These changes were mirrored by changes in other behavior rating scales. Sixty percent of subjects had no side effects; 33% had side effects that were rated as mild. There were no clinically significant changes in laboratory values. CONCLUSION: Ongoing open-label treatment with divalproex was associated with improvement in measures of agitation. Doses, levels, and tolerability were similar to those in the blinded phase of the study. These findings help confirm and extend the results from the placebo-controlled phase of the trial and suggest that divalproex may be beneficial for some patients with this clinical problem.

Streim JE, Porsteinsson AP, Breder CD, Swanink R, Marcus R, McQuade R, Carson WH. · Section on Geriatric Psychiatry, University of Pennsylvania, Philadelphia, PA 19104-3309, USA. · Am J Geriatr Psychiatry. · Pubmed #18591574 No free full text.

Abstract: OBJECTIVE: To evaluate the efficacy and safety of aripiprazole treatment for psychotic symptoms associated with Alzheimer disease (AD). METHODS: In this parallel group, randomized, double-blind, placebo-controlled, flexible-dose trial, institutionalized subjects with AD and psychotic symptoms were randomized to aripiprazole (n = 131) or placebo (n = 125) for 10 weeks. The aripiprazole starting dose was 2 mg/day, and could be titrated to higher doses (5, 10, and 15 mg/day) based on efficacy and tolerability. RESULTS: No significant differences in mean change [2 x SD] from baseline between aripiprazole (mean dose approximately 9 mg/day at endpoint; range = 0.7-15.0 mg) and placebo were detected in the coprimary efficacy endpoints of Neuropsychiatric Inventory-Nursing Home Version (NPI-NH) Psychosis score (aripiprazole, -4.53 [9.23]; placebo, -4.62 [9.56]; F = 0.02, df = 1, 222, p = 0.883 [ANCOVA]) and Clinical Global Impression (CGI)-Severity score (aripiprazole, -0.57 [1.63]; placebo, -0.43 [1.65]; F = 1.67, df = 1, 220, p = 0.198 [ANCOVA]) at endpoint. However, improvements in several secondary efficacy measures (NPI-NH Total, Brief Psychiatric Rating Scale Total, CGI - improvement, Cohen-Mansfield Agitation Inventory and Cornell Depression Scale scores) indicated that aripiprazole may confer clinical benefits beyond the primary outcome measures. Treatment-emergent adverse events (AEs) were similar in both groups, except for somnolence (aripiprazole, 14%; placebo, 4%). Somnolence with aripiprazole was of mild or moderate intensity, and not associated with accidental injury. Incidence of AEs related to extrapyramidal symptoms was low with aripiprazole (5%) and placebo (4%). CONCLUSIONS: In nursing home residents with AD and psychosis, aripiprazole did not confer specific benefits for the treatment of psychotic symptoms; but psychological and behavioral symptoms, including agitation, anxiety, and depression, were improved with aripiprazole, with a low risk of AEs.

Porsteinsson AP, Grossberg GT, Mintzer J, Olin JT, Anonymous00337. · Alzheimer's Disease Care, Research and Education Program, University of Rochester, School of Medicine and Dentistry, Rochester, NY 14620, USA. · Curr Alzheimer Res. · Pubmed #18288936 No free full text.

Abstract: OBJECTIVE: To evaluate the efficacy and safety of memantine in patients with mild to moderate Alzheimer's disease (AD) receiving cholinesterase inhibitor (ChEI) treatment. METHODS: Participants (N= 433) with probable AD, Mini-Mental State Exam (MMSE) scores between 10-22 (inclusive), and concurrent stable use of ChEIs (donepezil, rivastigmine, galantamine) were randomized to placebo or memantine (20 mg once daily) for 24 weeks. Primary outcomes were changes from baseline on the Alzheimer's Disease Assessment Scale-cognitive subscale (ADAS-cog) and on Clinician's Interview-Based Impression of Change Plus Caregiver Input (CIBIC-Plus) score. Secondary measures comprised the 23-item Alzheimer Disease Cooperative Study-Activities of Daily Living Scale (ADCS-ADL(23)), Neuropsychiatric Inventory (NPI), and MMSE. RESULTS: At the end of the trial, there were no statistically significant differences between the memantine- and placebo group on primary and secondary outcome measures. The incidence of adverse events (AEs) was similar between the two groups, with no AE occurring in more than 5% of memantine-treated patients and at a rate twice that of the placebo group. CONCLUSIONS: In this trial, memantine did not show an advantage over placebo based on protocol-specified primary or secondary analyses in patients with mild to moderate AD on stable ChEI regimens. There were no significant differences in tolerability and safety between the memantine- and placebo groups.

Martin BK, Frangakis CE, Rosenberg PB, Mintzer JE, Katz IR, Porsteinsson AP, Schneider LS, Rabins PV, Munro CA, Meinert CL, Niederehe G, Lyketsos CG. · Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA. · Am J Geriatr Psychiatry. · Pubmed #17068314 No free full text.

Abstract: OBJECTIVE: Research on the efficacy of antidepressant therapy for depressive symptoms in Alzheimer disease has been hampered by lack of systematic diagnosis, small sample sizes, and short-term follow up. To address these issues, the authors present the design of the Depression in Alzheimer's Disease Study-2 (DIADS-2), a randomized, placebo-controlled multicenter trial to evaluate the efficacy and safety of the selective serotonin reuptake inhibitor sertraline for the treatment of depression in people with Alzheimer disease. METHODS: The authors present and discuss the following important aspects of the design: the inclusion of structured psychosocial therapy for the caregivers of all participants; the measurement not only of patient mood outcomes, but also of global and functional outcomes for patients and mood and burden outcomes for caregivers; the ongoing rating of multiple diagnostic criteria to allow nosologic study of depression in Alzheimer disease; the evaluation of both short-term efficacy and longer-term outcomes; the follow up of all patients regardless of whether they complete study treatment; and the unmasking of treatment assignment at the conclusion of each patient's treatment phase. CONCLUSIONS: The authors believe these design elements are important features to be included in trials of depression and other neuropsychiatric disturbances in Alzheimer disease.

Rosenberg PB, Onyike CU, Katz IR, Porsteinsson AP, Mintzer JE, Schneider LS, Rabins PV, Meinert CL, Martin BK, Lyketsos CG, Anonymous00389. · Division of Geriatric Psychiatry and Neuropsychiatry, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA. · Int J Geriatr Psychiatry. · Pubmed #15660424 No free full text.

Abstract: OBJECTIVES: 'Depression of Alzheimer's Disease' (dAD) is a common complication of Alzheimer's disease and is increasingly recognized as a syndrome with a clinical presentation differing from major depression. Criteria for the diagnosis of dAD have been proposed previously. METHODS: This paper presents these criteria in operationalized format designed to be accessible for clinical use. Four cases are discussed that demonstrate the use of these criteria and illustrate important differences between dAD and major depression. RESULTS: The dAD criteria are broader than DSM-IV criteria for Major Depressive Episode and incorporate caregiver input. CONCLUSIONS: Given the differences between dAD and major depression diagnoses, it is important to assess the efficacy of treatments for dAD. Depression in Alzheimer's Disease-2 (DIADS-2) is a controlled trial of dAD treatments that will also assess the validity of these criteria.