Jason T. Olin

Validity and Reliability of the Alzheimer’s Disease Cooperative Study-Clinical Global Impression of Change (ADCS-CGIC)

Clinical global impressions of change (CGICs) are important measures of efficacy in clinical trials. CGIC scales have been used extensively as primary outcome criteria in psychopharmacological trials and in early clinical trials for antidementia drugs (e.g., Schneider and Olin, 1994). CGICs have been reported to be the most sensitive index of change in 14 of 17 dementia trials, when compared to other measures (Lehmann, 1984).

Provisional Diagnostic Criteria for Depression of Alzheimer Disease: Rationale and Background

This review provides the rationale and background for the development of diagnostic criteria for depression of Alzheimer disease (AD), including risk factors and neurobiological correlates, epidemiology, and clinical characteristics, along with course, assessment, treatment, economics, a description of the criteria, and future research directions. Overall, there is substantial research to suggest that the depression that may co-occur with AD is different from other depressive disorders. Further research is needed to better define core symptoms, clinical course, and efficacy of treatments.

Depression in Alzheimer's disease: overview and treatment.

Psychiatric disturbances affect as many as 90% of patients with Alzheimers disease (AD) and are a major focus of treatment. Depression is one of the most frequent psychiatric complications of AD, affecting as many as 50% of patients. In this context, depression is a significant public health problem that has a series of serious adverse consequences for patients and their caregivers. There has been little research into the course or treatment of depression associated with AD. This is in part due to the absence of validated operational criteria for defining depression in AD. Recently, the National Institute of Mental Health (NIMH) convened an expert consensus panel to develop draft criteria for depression of Alzheimers disease (NIMH-dAD) and to establish research priorities in this area. This article provides an overview of recent knowledge with regard to depression in AD with a special emphasis on its treatment. We conclude with recommendations for further research in this area.

Comorbidity of depression with other medical diseases in the elderly.

A major factor in the context of evaluating depression in the elderly is the role of medical problems. With aging there is a rapid increase in the prevalence of a number of medical disorders, including cancer, heart disease, Parkinsons disease, Alzheimers disease, stroke, and arthritis. In this article, we hope to bring clarity to the definition of comorbidity and then discuss a number of medical disorders as they relate to depression. We evaluate medical comorbidity as a risk factor for depression as well as the converse, that is, depression as a risk factor for medical illness. Most of the disorders that we focus on occur in the elderly, with the exception of HIV infection. This review focuses exclusively on unipolar disorder. The review summarizes the current state of the art and also makes recommendations for future directions.

Comorbidity of late life depression: an opportunity for research on mechanisms and treatment.

Late life depression principally affects individuals with other medical and psychosocial problems, including cognitive dysfunction, disability, medical illnesses, and social isolation. The clinical associations of late life depression have guided the development of hypotheses on mechanisms predisposing, initiating, and perpetuating specific mood syndromes. Comorbidity studies have demonstrated a relationship between frontostriatal impairment and late life depression. Further research has the potential to identify dysfunctions of specific frontostriatal systems critical for antidepressant response and to lead to novel pharmacological treatments and targeted psychosocial interventions. The reciprocal interactions of depression with disability, medical illnesses, treatment adherence, and other psychosocial factors complicate the care of depressed older adults. Growing knowledge of the clinical complexity introduced by the comorbidity of late life depression can guide the development of comprehensive treatment models. Targeting the interacting clinical characteristics associated with poor outcomes has the potential to interrupt the spiral of deterioration of depressed elderly patients. Treatment models can be most effective if they focus on amelioration of depressive symptoms, but also on treatment adherence, prevention of relapse and recurrence, reduction of medical burden and disability, and improvement of the quality of life of patients and their families.

National Institute of Mental Health Clinical Antipsychotic Trials of Intervention Effectiveness (CATIE): Alzheimer Disease Trial Methodology

The authors describe the development of the Clinical Antipsychotic Trials of Intervention Effectiveness (CATIE) protocol for Alzheimer disease (AD), a trial developed in collaboration with the National Institute of Mental Health (NIMH), assessing the effectiveness of atypical antipsychotics for psychosis and agitation occurring in AD outpatients. They provide an overview of the methodology utilized in the trial as well as the clinical-outcomes and effectiveness measures that were implemented.

Assessment of late life depression

This article focuses on diagnostic and nosologic challenges intrinsic to geriatric depression, including characteristics interfering with symptom and syndrome ascertainment, the impact of medical and cognitive disorders, the usefulness of screening instruments, and barriers imposed by treatment settings. The article also identifies gaps in existing knowledge and outlines a research agenda. Nosologic characterization of depressives syndromes contributed by specific medical disorders may lead to effective strategies for prevention and treatment of depression. Studies need to examine whether treatment of depression can improve the outcome of medical illnesses requiring active patient involvement in treatment. Considering disability a distinct aspect of health status may add an important dimension to the assessment of depression and result in complementary interventions aimed at depression and disability concurrently. The provisional criteria for depression of Alzheimers disease, if validated, may facilitate treatment research. Studies need to characterize cognitive dysfunctions associated with later development of dementia or poor treatment response in patients with depression. Care managers working together with primary care physicians can improve the recognition and treatment of depressed elderly patients by obtaining the training in using validated instruments and treatment algorithms.

Eligibility of Alzheimer's Disease Clinic Patients for Clinical Trials

OBJECTIVES: To identify the percentage of patients with Alzheimers disease (AD) in a general clinic population who would be provisionally eligible for randomized clinical trials and the extent to which these patients represent the overall clinic‐based population.

The Geriatric Depression Scale and the Beck Depression Inventory as screening instruments in an older adult outpatient population.

Older adult outpatients with major depression (n=25) and healthy control subjects (n=25) were compared using the Geriatric Depression Scale (GDS) and the Beck Depression Inventory (BDI). Both measures were sensitive in detecting clinical depression. Subjects were, however, more likely to endorse multiple responses in BDI items, suggesting that the GDS is simpler for older adults to complete. Viewed within the context of previous relevant research that used these instruments to compare older dults, our results yield additional evidence of cross-study consistency in the functional efficiency of both measures

A Pilot Randomized Trial of Carbamazepine for Behavioral Symptoms in Treatment-Resistant Outpatients with Alzheimer Disease

The authors performed a 6-week, randomized, double-blind, placebo-controlled, parallel-group trial of carbamazepine (400 mg/day) with 21 agitated subjects (16 completers) who had been treated unsuccessfully with antipsychotics. There was greater improvement for the carbamazepine group on the Clinical Global Impression of Change (P=0.055) and the Brief Psychiatric Rating Scale (BPRS) Hostility item (P=0.009), with a trend toward worsening on the BPRS Hallucination item (P=0.067). Overall, carbamazepine showed modest clinical benefit in these subjects, who had not responded to antipsychotics, and particular benefit for hostility. The effect on global ratings was similar to those found in an earlier report in nursing home residents.