Alzheimer Disease: Steele CD

Steele CD. · Department of Psychiatry and Behavioral Sciences, School of Medicine, and Faculty Associate, School of Nursing, The Johns Hopkins University, Baltimore, Maryland 21287, USA. · Nurs Clin North Am. · Pubmed #10957683 No free full text.

Abstract: Alzheimer disease (AD) is the most common cause of dementia in late life. AD has been described as early onset, occurring at or younger than age 50, or late onset, occurring at or older than age 70. Although AD is a genetically heterogeneous disorder, it is classified as familial or sporadic. Cases in which a clear pattern of inheritance within a family is established are termed familial Alzheimer disease (FAD). Sporadic, however, is problematic when studying a late onset disease such as AD. It is likely that people who may carry a mutation die of another cause before reaching the age of risk. This article describes the known genetic mutations resulting in an autosomal dominant pattern of inheritance in early onset AD and a polymorphism associated with the more common late onset disorder.

Munro CA, Brandt J, Sheppard JM, Steele CD, Samus QM, Steinberg M, Rabins PV, Lyketsos CG. · Division of Medical Psychology, Department of Psychiatry and Behavioral Sciences, School of Medicine, The Johns Hopkins University, Baltimore, MD, USA. · Am J Geriatr Psychiatry. · Pubmed #15353387 No free full text.

Abstract: OBJECTIVE: The authors assessed the cognitive effects of depression treatment with sertraline in patients with Alzheimer disease (AD) and major depression. METHODS: Forty-four patients with probable AD and major depression were enrolled in a double-blind, placebo-controlled clinical trial of sertraline. Cognitive testing was done at baseline and at 3-week intervals throughout the 12-week study. At the 12th week, subjects were categorized by treatment response (full, partial, or no response). Cognitive data from 41 participants who completed three or more testing sessions and 36 who completed all five study visits were included in the analyses. RESULTS: Neither improved mood nor use of sertraline was associated with cognitive change over time in AD patients. Post-hoc exploration of the data, however, suggested a sex difference in cognitive response to sertraline such that women treated with sertraline demonstrated improved cognition compared with women on placebo, whereas men treated with sertraline worsened significantly in cognition compared with men on placebo. CONCLUSIONS: In this study, among depressed AD patients after treatment with sertraline or placebo, there was no evidence that improved mood was associated with cognitive improvement. Future studies aimed at increasing power to detect mood as well as medication effects will be valuable in determining the relationship between cognition and treatment of depression in AD patients.

Lyketsos CG, DelCampo L, Steinberg M, Miles Q, Steele CD, Munro C, Baker AS, Sheppard JM, Frangakis C, Brandt J, Rabins PV. · Division of Geriatric Psychiatry and Neuropsychiatry, Department of Psychiatry and Behavioral Sciences, School of Medicine, The Johns Hopkins University, Baltimore, MD, USA. · Arch Gen Psychiatry. · Pubmed #12860778 links to  free full text

Abstract: CONTEXT: Major depression affects about 25% of the patients who have Alzheimer disease and has serious adverse consequences for patients and caregivers. Results of prior antidepressant treatment studies have produced contradictory findings and have not fully assessed the benefits of depression reduction. OBJECTIVES: To assess the efficacy and safety of sertraline hydrochloride for the treatment of major depression in Alzheimer disease, and to evaluate the effect of depression reduction on activities of daily living, cognition, and nonmood behavioral disturbance. DESIGN: Randomized, placebo-controlled, parallel, 12-week, flexible-dose clinical trial with a 1-week, single-blind placebo phase. The study was conducted between January 1, 1998, and July 19, 2001. SETTING: University outpatient clinic. PARTICIPANTS: Forty-four outpatients who have probable Alzheimer disease and major depressive episodes. INTERVENTION: Sertraline hydrochloride, mean dosage of 95 mg/d, or identical placebo, randomly assigned. MAIN OUTCOME MEASURES: Response rate, Cornell Scale for Depression in Dementia, Hamilton Depression Rating Scale, Mini-Mental State Examination, Psychogeriatric Depression Rating Scale-activities of daily living subscale, and Neuropsychiatric Inventory to quantify patient behavior disturbance and caregiver distress. RESULTS: In the sertraline-treated group 9 patients (38%) were full responders and 11 (46%) were partial responders compared with 3 (20%) and 4 (15%), respectively, in the placebo-treated group (P =.007). The sertraline-treated group had greater improvements in the scores for the Cornell Scale for Depression in Dementia (P =.002) and Hamilton Depression Rating Scale (P =.01), and a statistical trend toward less decline in activities of daily living on the Psychogeriatric Depression Rating Scale-activities of daily living subscale (P =.07). There was no difference between the treatment groups in Mini-Mental State Examination (P =.22) or Neuropsychiatric Inventory (P =.32) ratings over time. When full responders, partial responders, and nonresponders were compared, full responders only, or full and partial responders had significantly better ratings on activities of daily living (P =.04), behavioral disturbance (P =.01), and caregiver distress (P =.006), but not on the Mini-Mental State Examination (P =.76). Safety monitoring indicated few differences in adverse effects between the 2 treatment groups. CONCLUSIONS: Sertraline is superior to placebo for the treatment of major depression in Alzheimer disease. Depression reduction is accompanied by lessened behavior disturbance and improved activities of daily living, but not improved cognition.

Lyketsos CG, Sheppard JM, Steele CD, Kopunek S, Steinberg M, Baker AS, Brandt J, Rabins PV. · Department of Psychiatry and Behavioral Sciences, School of Medicine, Johns Hopkins University, Baltimore, USA. · Am J Psychiatry. · Pubmed #11007727 links to  free full text

Abstract: OBJECTIVE: This study evaluated the efficacy and safety of sertraline in the treatment of major depression in 22 outpatients with Alzheimer's disease. METHOD: Twelve of the 22 patients were given sertraline and 10 were given placebo by random group assignment for 12 weeks. Response to treatment was measured by using the Cornell Scale for Depression in Dementia. The patients were also assessed with the Hamilton Depression Rating Scale, the activities of daily living subscale of the Psychogeriatric Dependency Rating Scales, and the Mini-Mental State. RESULTS: After 12 weeks of double-blind, placebo-controlled treatment, nine of the patients given sertraline and two of those given placebo were at least partial responders. Patients given sertraline had significantly greater mean declines from baseline in Cornell Scale for Depression in Dementia scores; the bulk of antidepressant response occurred by the third week of treatment. CONCLUSIONS: Sertraline is superior to placebo in reducing depression in patients with Alzheimer's disease who also suffer from major depression.

Bassiony MM, Rosenblatt A, Baker A, Steinberg M, Steele CD, Sheppard JM, Lyketsos CG. · Division of Geriatric Psychiatry and Neuropsychiatry, Department of Psychiatry and Behavioral Science, School of Medicine, Johns Hopkins University, Baltimore, MD, USA. · J Nerv Ment Dis. · Pubmed #15387161 No free full text.

Abstract: The study's objective was to estimate the prevalence of falls in community-residing patients with Alzheimer's disease (AD) and to investigate the relationship between falls and age in AD. This was a study of 326 community-residing patients with AD according to National Institute of Neurological and Communicative Disorders and Stroke and Alzheimer's Disease and Related Disorders Association criteria. The patients and their caregivers were asked about falls, behavioral disturbances, and medication use within the last 2 weeks. The patients were also rated on standardized measures of cognitive impairment, stage of dementia, depression, daily activities, general health, and extrapyramidal symptoms. Falls occurred in 24 (7.4%) patients with AD during the last 2 weeks. Using multiple logistic regression analyses, falls were independently associated with old age (odds ratio = 1.2; p = .03; 95% confidence interval = 1.0 to 1.4) but not with other variables examined. The authors conclude that falls in community-residing patients with AD are significantly associated with old age. Population-based prospective studies are needed to investigate further the risk factors for falls in AD.

Bassiony MM, Warren A, Rosenblatt A, Baker A, Steinberg M, Steele CD, Sheppard JM, Lyketsos CG. · Department of Psychiatry, Faculty of Medicine, Zagazig University, Egypt. · Int J Geriatr Psychiatry. · Pubmed #12112179 No free full text.

Abstract: OBJECTIVES: The aim of this investigation was to study the relationship between delusions and depression in Alzheimer's disease (AD). DESIGN: This was a cross-sectional, case control study. SETTING: Neuropsychiatry Service, the Johns Hopkins School of Medicine, USA. PARTICIPANTS: 303 community-residing patients with probable AD according to NINCDS/ADRDA criteria were included in the study. Seventy-five patients with delusions only were compared to a control group of 228 patients who had neither delusions nor hallucinations. Patients with only hallucinations or both delusions and hallucinations were excluded. MEASURES: Patients were assessed clinically for the presence of delusions using the DSM-IV glossary definitions. They were also rated on standardized measures of depression, cognitive impairment, staging of dementia, general medical health, and functional impairment. RESULTS: There was an association between delusions and depression among patients with AD. Before adjustment for other variables, the presence of depression conferred a 1.8-fold (95% confidence intervals (CI) = 1.0-3.1; p = 0.04) higher risk of delusions. After adjustment for multiple other variables, this risk increased further to 6.8-fold (95% CI = 2.1-21.6; p = 0.001). CONCLUSIONS; Delusions in AD are strongly associated with depression after statistical adjustment for all confounding variables, which might distort this association. This finding has implications for our understanding of the etio-pathogenesis and management of delusions and depression in AD.

Bassiony MM, Warren A, Rosenblatt A, Baker A, Steinberg M, Steele CD, Lyketsos CG. · Neuropsychiatry Service, Department of Psychiatry and Behavioral Science, School of Medicine, The Johns Hopkins University, USA. · Int J Geriatr Psychiatry. · Pubmed #11921146 No free full text.

Abstract: OBJECTIVES: The aim of this investigation was to study the relationship between isolated hallucinosis and race in Alzheimer's disease. METHODS: This was a cross-sectional, case control study carried out at the Neuropsychiatry Service, outpatient clinic at the Johns Hopkins School of Medicine, USA. The participants were 237 community-residing patients with probable Alzheimer's disease according to NINCDS/ADRDA criteria were included in the study. 9 patients with isolated hallucinosis were compared to a control group of 228 patients who had neither delusions nor hallucinations. Patients with only delusions or both delusions and hallucinations were excluded based on prior research. Patients were assessed clinically for the presence of hallucinations using the DSM-IV glossary definitions. They were also rated on standardized measures of cognitive impairment, depression, functional impairment, and general health. RESULTS: There was a significant association between hallucinations and race in patients with Alzheimer's disease. Before adjustment for other variables, the African-American race conferred a 5.5-fold (95% CI = 1.4-21.6; p = 0.02) increased risk for isolated hallucinosis. After adjustment for multiple other variables, this risk increased further to 27.2-fold (95% CI = 1.6-457.3; p = 0.02). CONCLUSIONS: African-American patients with Alzheimer's disease are more likely to have isolated hallucinations than Caucasian patients even after statistical adjustment for multiple confounding variables, which might distort this association. This finding has implications for our understanding of the etio-pathogenesis of hallucinations in Alzheimer's disease and for meeting health service needs of African-American patients.