A systematic review of antidepressant placebo-controlled trials for geriatric depression: limitations of current data and directions for the future.

Depression in the elderly is a major public health problem as untreated depression adversely impacts comorbid illnesses. It is important to develop safe and effective antidepressant therapies for older individuals. We performed a systematic review of all published randomized, placebo-controlled antidepressant medication trials in populations over age 55 years.

Marked increase in Alzheimer's disease identified in medicare claims records between 1991 and 1999.

Background: Epidemiologic evidence suggests that African Americans have higher rates of Alzheimer's disease (AD) than do whites. Examining longitudinal trends in the number of persons who are identified as having AD in administrative databases may provide insights into this phenomenon.

Methods: We analyzed 9-year longitudinal data (1991-1999) for 29,679 Medicare beneficiaries who were screened for the National Long-Term Care Survey.

Metals in our minds: therapeutic implications for neurodegenerative disorders.

Background: Abnormal interactions of copper or iron in the brain with metal-binding proteins (such as amyloid-beta peptide [Abeta] or neuromelanin) that lead to oxidative stress have emerged as important potential mechanisms in brain ageing and neurodegenerative disorders. Although a controlled study of desferrioxamine in Alzheimer's disease(AD) had some promising results, concerns about toxicity and brain delivery have limited trials of traditional chelators. The therapeutic significance of metal dysregulation in neurodegenerative disorders has remained difficult to test.

Effect of Bupropion SR on the Quality of Life of Elderly Depressed Patients With Comorbid Medical Disorders.

BACKGROUND: There is a need for additional studies of the quality of life (QOL) of elderly depressed subjects with medical comorbidity. METHOD: We conducted an 8-week, open trial of bupropion sustained release (SR) in 18 elderly (60-81 years) subjects with DSM-IV major depressive disorder and one or more serious medical illnesses (e.g.

In vivo amyloid imaging in Alzheimer's disease.

Targeted approaches to therapy for Alzheimer's disease have evolved based on detailed understanding of the genetic, molecular biologic, and neuropathologic basis of the disease. Given the potential for greater treatment efficacy in the earlier stages of the disease, the notion of early diagnosis has become more relevant. Current clinical and imaging diagnostic approaches lack reliability in the preclinical and prodromal phases of the disease.

Efficacy, safety, and tolerability of sertraline in patients with late-life depression and comorbid medical illness.

Objectives: To report on the efficacy, safety, and tolerability of sertraline in the treatment of elderly depres-sed patients with and without comorbid medical illness.

Setting: Multicenter.

Design: Randomized, double-blind, placebo-controlled study.

Does antidepressant therapy improve cognition in elderly depressed patients?

Objectives: To analyze the effects of antidepressants on cognitive functioning in elderly depression.

Methods: Data were pooled for elderly participants with major depression from two double-blind 12-week studies (n = 444) comparing sertraline to fluoxetine and to nortriptyline. A cognitive battery was performed pre-treatment and post-treatment that included the Shopping List Task (SLT), which quantifies short-term and long-term memory storage and retrieval, and the Digit Symbol Substitution Test (DSST), which measures visual tracking, motor performance, and coding.

Therapeutic implications of HPA axis abnormalities in Alzheimer's disease: review and update.

The adaptive and maladaptive roles of the hypothalamic-pituitary-adrenal (HPA) axis in stressful conditions and in disorders such as major depression, posttraumatic stress disorder, and Cushing's syndrome, have been the subject of substantial, ongoing study. In particular, HPA disturbances have been associated with memory impairments, and hypercortisolemic conditions with atrophy of the hippocampus, a limbic structure closely associated with declarative memory. Recent discoveries support a more complicated picture of HPA axis function and pathology in acquiring, retrieving, and consolidating new memories.

Randomized, placebo-controlled trial of the effects of donepezil on neuronal markers and hippocampal volumes in Alzheimer's disease.

Objective: The authors examined the effect of the acetylcholinesterase inhibitor donepezil on magnetic resonance markers of neurodegeneration in Alzheimer's disease.

Method: In this randomized, double-blind, placebo-controlled pilot study, 67 patients with mild to moderate Alzheimer's disease received 24 weeks of treatment with donepezil (5 mg/day for the first 28 days and 10 mg/day thereafter) or placebo. Patients were reevaluated at 6-week intervals to measure change from baseline in several outcome measures, including right, left, and total hippocampal volumes, measured with magnetic resonance imaging; brain concentrations of N-acetylaspartate, measured with proton magnetic resonance spectroscopy; and cognition, assessed with the Alzheimer's Disease Assessment Scale cognitive subscale.

Alzheimer's disease and the glutamate NMDA receptor.

Current treatment of Alzheimer's disease (AD) has focused on the use of cholinesterase inhibitors. This review emphasizes emerging therapies for the treatment and/or prevention of AD with a focus on glutamatergic excitotoxicity in dementia and the therapeutic promise of the uncompetitive, low to moderate affinity N-methyl-D-aspartate (NMDA) receptor antagonist, memantine. Preclinical studies and clinical trials in AD, as well as the extensive clinical use of memantine for neurodegenerative conditions in Europe since 1982 support the safety, tolerability, and efficacy of this agent.

Pancreatitis associated with atypical antipsychotics: from the Food and Drug Administration's MedWatch surveillance system and published reports.

Study Objective: To investigate the relative numbers and clinical characteristics of pancreatitis in patients treated with the atypical antipsychotic agents, clozapine, olanzapine, and risperidone, versus the conventional neuroleptic, haloperidol.

Design: Pharmacovigilance study of pooled, spontaneously reported adverse events.

Setting: Government-affiliated drug evaluation center.

The role of the N-methyl-D-aspartate receptor in Alzheimer's disease: therapeutic potential.

Alzheimer's disease (AD) is a progressive neurodegenerative disorder with an unknown etiology. Pathologic processes implicated in AD include b-amyloid-induced synaptic failure; tau hyperphosphorylation; inflammation; oxidative stress; abnormal neurotransmission involving acetylcholine, glutamate, norepinephrine, serotonin, and dopamine; and abnormalities in second messengers, protein kinases, and apoptosis. Although each of these pathways offers potential therapeutic targets, pharmacologic manipulation of the glutamatergic N-methyl-D-aspartate receptor pathway, alone or in combination with cholinergic therapies, is emerging as the next promising strategy for the treatment of AD and vascular dementia.

Current status of metals as therapeutic targets in Alzheimer's disease.

There is accumulating evidence that interactions between beta-amyloid and copper, iron, and zinc are associated with the pathophysiology of Alzheimer's disease (AD). A significant dyshomeostasis of copper, iron, and zinc has been detected, and the mismanagement of these metals induces beta-amyloid precipitation and neurotoxicity. Chelating agents offer a potential therapeutic solution to the neurotoxicity induced by copper and iron dyshomeostasis.

Statin-associated memory loss: analysis of 60 case reports and review of the literature.

Objective: To review case reports of statin-associated memory loss as well as the available published evidence for and against such a link.

Methods: We searched the MedWatch drug surveillance system of the Food and Drug Administration (FDA) from November 1997-February 2002 for reports of statin-associated memory loss. We also reviewed the published literature (using MEDLINE) and prescribing information for these drugs.

The Q7R Saitohin gene polymorphism is not associated with Alzheimer disease.

Previous studies have reported conflicting results regarding the association of the Q7R polymorphism in the Saitohin gene with late-onset Alzheimer disease (AD). Given that AD is a tauopathy but no mutations or polymorphisms in Tau have been consistently associated with AD, and that Saitohin is nested in intron 9 of Tau and shares a similar expression pattern, we tested this association in 690 multiplex AD families and in a case-control sample (903 patients and 320 controls). We found no evidence of significant association of this polymorphism with risk of AD using family-based and case-control tests of association.

Risperidone-associated diabetes mellitus: a pharmacovigilance study.

Study Objective: To explore the clinical characteristics of hyperglycemia in patients treated with risperidone.

Design: Pharmacovigilance survey of spontaneously reported adverse events in risperidone-treated patients, with reports of haloperidol-associated hyperglycemia used as a control.

Setting: Government-affiliated drug evaluation center.

Neuroimaging and early diagnosis of Alzheimer disease: a look to the future.

Alzheimer disease (AD), a progressive neurodegenerative disorder, is the most common cause of dementia in the elderly. Current consensus statements have emphasized the need for early recognition and the fact that a diagnosis of AD can be made with high accuracy by using clinical, neuropsychologic, and imaging assessments. Magnetic resonance (MR) or computed tomographic (CT) imaging is recommended for the routine evaluation of AD.

Donepezil for the treatment of language deficits in adults with Down syndrome: a preliminary 24-week open trial.

At present, there is no proven pharmacologic treatment for cognitive or language impairments in Down syndrome (DS). Cholinergic deficits have been documented in DS and linked to cognitive deficits. This study is a 24-week open-label clinical trial of donepezil hydrochloride for the treatment of language deficits in adults with DS.

Exercise therapy for depression in middle-aged and older adults: predictors of early dropout and treatment failure.

Psychosocial factors predicting treatment dropout or failure to benefit from treatment were identified in a randomized trial of exercise therapy and pharmacotherapy for major depression. One hundred fifty-six men and women over age 50 diagnosed with major depressive disorder were assigned to a 16-week program of aerobic exercise, medication (sertraline), or a combination of exercise and medication. Thirty-two patients (21%) failed to complete the program and were considered treatment "dropouts.

Non-cholinergic strategies for treating and preventing Alzheimer's disease.

The pathophysiology of Alzheimer's disease is complex and involves several different biochemical pathways. These include defective beta-amyloid (Abeta) protein metabolism, abnormalities of glutamatergic, adrenergic, serotonergic and dopaminergic neurotransmission, and the potential involvement of inflammatory, oxidative and hormonal pathways. Consequently, these pathways are all potential targets for Alzheimer's disease treatment and prevention strategies.