Alzheimer Disease: Sheppard JM

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.

Payne JL, Sheppard JM, Steinberg M, Warren A, Baker A, Steele C, Brandt J, Lyketsos CG. · Neuropsychiatry Service, Department of Psychiatry and Behavioral Sciences, School of Medicine, The Johns Hopkins University, 600 N Wolfe Street, Baltimore, MD 21287, USA. · Int J Geriatr Psychiatry. · Pubmed #11921153 No free full text.

Abstract: BACKGROUND: The course of depression in residents of long-term care with dementia is not well studied. OBJECTIVES: To estimate the incidence, prevalence, and outcomes of depression in long-term care residents with dementia. METHOD: 201 residents of Copper Ridge, a long-term care facility for the memory impaired, were followed every six months during the first year after their admission. RESULTS: On admission 19.9% of the residents had depression, the majority (75%) occurring in persons with a prior history of depression. At six months, only 15% of the original 40 depressed patients were still depressed, while at twelve months only 7.5% were depressed. The incidence of depression at six and twelve months was 1.8% and 6.4% respectively. Most persons with new depression at six months were no longer depressed at one year. The annual attack rate (cumulative likelihood of depression over one year) for the total population was 26.4%. The rates for the subgroup of Alzheimer's were similar to the rates of the total population, except for an annual attack rate of 17.5%, reflecting a lower rate of depression on admission. The decline in depression over the year after admission is noteworthy and likely reflects appropriate diagnosis and treatment of depression. CONCLUSIONS: These results indicate that, over the course of one year, depression afflicts a considerable proportion of long-term care residents with dementia. Admission to a long-term care facility may actually result in a reduction of depression within the year after admission in part due to rapid recognition, appropriate diagnosis and treatment.

Lyketsos CG, Sheppard JM, Steinberg M, Tschanz JA, Norton MC, Steffens DC, Breitner JC. · Neuropsychiatry Service, Department of Psychiatry and Behavioral Sciences, School of Medicine, Johns Hopkins University, USA. · Int J Geriatr Psychiatry. · Pubmed #11746650 No free full text.

Abstract: OBJECTIVE: We investigated the frequency and inter-relationship of neuropsychiatric disturbances in a population sample of persons suffering from Alzheimer's disease (AD). METHOD: Screening 5,092 elderly residents (90% of the population aged 65 and older) of Cache County, Utah, for dementia, we identified 198 persons with AD using a comprehensive neuropsychiatric examination protocol. This examination included the Neuropsychiatric Inventory (NPI), a widely used measure of dementia-associated neuropsychiatric disturbances. RESULTS: Overall, 60% of individuals with AD reported one or more neuropsychiatric symptoms. A latent class analysis revealed that these participants could be classified into three groups (classes) based on their neuropsychiatric symptom profile. The largest class included cases with no neuropsychiatric symptoms (40%) or with a mono-symptomatic disturbance (19%). A second class (28%) exhibited a predominantly affective syndrome, while a third class (13%) had a psychotic syndrome. CONCLUSION: Data from this first US population-based study of AD-associated neuropsychiatric disturbances suggest that a significant majority of persons with AD suffer from one or more neuropsychiatric disturbance. Based on phenomenological study, the spectrum of neuropsychiatric symptoms in AD can be empirically classified into three groups: an affective syndrome, a psychotic syndrome and other neuropsychiatric disturbance. The biologic and predictive validity of this classification merits further investigation.

Klein DA, Steinberg M, Galik E, Steele C, Sheppard JM, Warren A, Rosenblatt A, Lyketsos CG. · Department of Psychiatry and Behavioral Sciences, School of Medicine, Johns Hopkins University, Baltimore, MD 21287, USA. · Int J Geriatr Psychiatry. · Pubmed #10340188 No free full text.

Abstract: OBJECTIVES: To examine wandering behaviour in elderly demented persons in the community setting with respect to dementia characteristics and other factors that might influence wandering behaviour; to generate a statistical model to assess the relative importance of these various factors in predicting wandering behaviour. DESIGN: Cross-sectional, case-control investigation. SETTING: University-affiliated outpatient neuropsychiatric assessment center. PARTICIPANTS: Six hundred and thirty-eight consecutive community-residing new patients with dementia referred for evaluation. MEASUREMENTS: Comprehensive neuropsychiatric evaluation, including rating with Mini-Mental State Examination; General Medical Health Rating; Comell Scale of Depression in Dementia and caregiver interview. RESULTS: Wandering behaviour occurred in 17.4% of participants. It was significantly more prevalent in patients with Alzheimer Dementia (AD), patients with dementia of longer duration, and patients with more severe dementia. Wandering behaviour was associated with moderate to severe depression, delusions, hallucinations, and sleep disorder. Other significant associations of wandering behaviour included use of neuroleptic medication and male gender. After statistical adjustment for other variables, duration of dementia, severity of dementia and presence of sleep disorder retained significant statistical association with wandering behaviour. CONCLUSIONS: Wandering behaviour among community-residing elderly dementia patients is associated with a number of factors, some of which may be subject to modification. It is possible that management of coexistent psychopathology, particularly of sleep disorder, and of the underlying disease process of AD would help to ameliorate this problematic behavioural disorder. Further investigation is warranted into the relationship between neuroleptic medication and wandering behaviour and into possible alternative measures to control agitation in elderly dementia patients.