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Biomedical subjects

Constantine G Lyketsos

Publications and source records attributed to Constantine G Lyketsos.

At least 19 recordsLinked to original sources
PubMed2006

Effectiveness of atypical antipsychotic drugs in patients with Alzheimer's disease.

BACKGROUND: Second-generation (atypical) antipsychotic drugs are widely used to treat psychosis, aggression, and agitation in patients with Alzheimer's disease, but their benefits are uncertain and concerns about safety have emerged. We assessed the effectiveness of atypical antipsychotic drugs in outpatients with Alzheimer's disease. METHODS: In this 42-site, double-blind, placebo-controlled trial, 421 outpatients with Alzheimer's disease and psychosis, aggression, or agitation were randomly assigned to receive olanzapine (mean dose, 5.5 mg per day), quetiapine (mean dose, 56.5 mg per day), risperidone (mean dose, 1.0 mg per day), or placebo. Doses were adjusted as needed, and patients were followed for up to 36 weeks. The main outcomes were the time from initial treatment to the discontinuation of treatment for any reason and the number of patients with at least minimal improvement on the Clinical Global Impression of Change (CGIC) scale at 12 weeks. RESULTS: There were no significant differences among treatments with regard to the time to the discontinuation of treatment for any reason: olanzapine (median, 8.1 weeks), quetiapine (median, 5.3 weeks), risperidone (median, 7.4 weeks), and placebo (median, 8.0 weeks) (P=0.52). The median time to the discontinuation of treatment due to a lack of efficacy favored olanzapine (22.1 weeks) and risperidone (26.7 weeks) as compared with quetiapine (9.1 weeks) and placebo (9.0 weeks) (P=0.002). The time to the discontinuation of treatment due to adverse events or intolerability favored placebo. Overall, 24% of patients who received olanzapine, 16% of patients who received quetiapine, 18% of patients who received risperidone, and 5% of patients who received placebo discontinued their assigned treatment owing to intolerability (P=0.009). No significant differences were noted among the groups with regard to improvement on the CGIC scale. Improvement was observed in 32% of patients assigned to olanzapine, 26% of patients assigned to quetiapine, 29% of patients assigned to risperidone, and 21% of patients assigned to placebo (P=0.22). CONCLUSIONS: Adverse effects offset advantages in the efficacy of atypical antipsychotic drugs for the treatment of psychosis, aggression, or agitation in patients with Alzheimer's disease. (ClinicalTrials.gov number, NCT00015548 [ClinicalTrials.gov].).

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PubMed2006

Race and restless legs syndrome symptoms in an adult community sample in east Baltimore.

BACKGROUND & PURPOSE: Due to the relative absence of African-Americans seeking treatment for restless legs syndrome (RLS) in specialty clinics, a lower prevalence of RLS among African-Americans than Caucasians has been suggested. We compared the prevalence of RLS in African-Americans and Caucasians in a biracial community sample as part of Wave IV of the Baltimore Health and Mental Health Study. METHODS: Subjects included 1071 adults [358 African-Americans (35.0%), and 633 Caucasians (61.8%), and 33 others]. Diagnosis of RLS was based on endorsement of RLS symptoms on a seven-item RLS questionnaire during a household interview. Adjusted odds and 95% confidence intervals were calculated based on logistic regression models with diagnosis of RLS as the main outcome variables and African-American race as the main predictor while adjusting for other relevant sociodemographic and/or health-related variables. RESULTS: The prevalence of RLS in this population was 4.1%. The rates were similar for African-Americans (4.7%) and Caucasians (3.8%). After adjustment for age, gender, medical comorbidities, and socioeconomic status, no difference in the prevalence of RLS was found between African-Americans and Caucasians. CONCLUSION: RLS is comparably prevalent among African-American and Caucasian adults in the general population. Barriers affecting access to care settings for African-American RLS patients should be investigated in the future.

Adult↗
PubMed2006

Antihypertensive medication use and incident Alzheimer disease: the Cache County Study.

BACKGROUND: Recent reports suggest that antihypertensive (AH) medications may reduce the risk of dementing illnesses. OBJECTIVES: To examine the relationship of AH medication use with incidence of Alzheimer disease (AD) among the elderly population (aged 65 years and older) of Cache County, Utah, and to examine whether the relationship varies with different classes of AH medications. METHODS: After an initial (wave 1) multistage assessment (1995 through 1997) to identify prevalent cases of dementia, we used similar methods 3 years later (wave 2) to identify 104 incident cases of AD among the 3308 survivors. At the baseline assessment, we obtained a detailed drug inventory from the study participants. We carried out discrete time survival analyses to examine the association between the use of AH medications (including angiotensin converting enzyme inhibitors, beta-blockers, calcium channel blockers, and diuretics) at baseline with subsequent risk of AD. RESULTS: Use of any AH medication at baseline was associated with lower incidence of AD (adjusted hazard ratio, 0.64; 95% confidence interval, 0.41-0.98). Examination of medication subclasses showed that use of diuretics (adjusted hazard ratio, 0.57; 95% confidence interval, 0.33-0.94), and specifically potassium-sparing diuretics (adjusted hazard ratio, 0.26; 95% confidence interval, 0.08-0.64), was associated with the greatest reduction in risk of AD. Corresponding analysis with a fully examined subsample controlling for blood pressure measurements did not substantially change our findings. CONCLUSIONS: These data suggest that AH medications, and specifically potassium-sparing diuretics, are associated with reduced incidence of AD. Because the latter association is a new finding, it requires confirmation in further study.

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PubMed2006

Perspectives on depression, mild cognitive impairment, and cognitive decline.

CONTEXT: The public health implications of depression and cognitive impairment in late life are enormous. Cognitive impairment and late-life depression are associated with increased risk for subsequent dementia; however, investigations of these phenomena appear to be proceeding along separate tracks. OBJECTIVES AND DATA SOURCE: The National Institute of Mental Health organized the conference "Perspectives on Depression, Mild Cognitive Impairment, and Cognitive Decline" to consider how the varied perspectives might be better integrated to examine the associations among depression, mild cognitive impairment, and cognitive decline and to illuminate the common or distinct mechanisms involved in these associations. DATA SYNTHESIS: The following 2 broad questions were addressed: (1) What gaps in our knowledge have the greatest public health significance? (2) Can we more efficiently use our research dollars and participant resources to fill these gaps? Meeting participants included grantees from the National Institute of Mental Health and the National Institute on Aging and program staff from the National Institute of Mental Health, the National Institute on Aging, and the National Institute of Neurological Disorders and Stroke. CONCLUSIONS: One of the most important recommendations to emerge from the meeting discussions is for increased collaboration among clinical and epidemiological investigators whose work focuses in the area of depression with those working primarily in the area of memory disorders. Directions for future research were identified.

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PubMed2006

A population-based study of the association between coronary artery bypass graft surgery (CABG) and cognitive decline: the Cache County study.

BACKGROUND: The relationship between coronary artery bypass graft (CABG) surgery and cognitive decline remains uncertain, in particular with regard to whether there is delayed cognitive decline associated with this procedure. METHODS: This was a population-based cohort study involving participants in the Cache County Study of Memory Health and Aging. At baseline the study enrolled 5,092 persons age 65 and older and followed them up three years later and again four years after that. Individuals who reported having undergone CABG surgery at study baseline or had this surgery in between follow-up waves were compared to individuals who never reported having the surgery. The main outcome measure was the Modified Mini Mental State (3MS). Multilevel models were used to examine the relationship between CABG surgery and cognitive decline over time. RESULTS: Study participants who had CABG surgery evidenced 0.95 points of greater decline relative to baseline on the 3MS at the first follow-up interview after CABG, and an average of 1.9 points of greater decline at the second follow-up interview, than those without CABG (t = -2.51, df = 2,316, p = 0.0121), after adjusting for several covariates, including number of vascular conditions. This decline was restricted to individuals who were more than five years past the procedure and was not evident in the early years after the surgery. CONCLUSIONS: CABG surgery is associated with accelerated cognitive decline more than five years after the procedure in a long-lived population. This decline is small and its clinical significance is uncertain. We could not find an association between CABG and decline in the first five post-operative years.

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PubMed2006

Comparison of three rating scales as outcome measures for treatment trials of depression in Alzheimer disease: findings from DIADS.

CONTEXT: Major depression affects about 25% of patients with Alzheimer's disease (AD) and has serious adverse consequences for patients as well as caregivers. Studies of treatments for depression in AD, like most treatment studies, depend on the ability of the scales used to measure outcome to detect a difference between the effects of treatment and control, particularly in trials conducted over waves. OBJECTIVE: To compare the ability of three depression scales, and some of their subscales, to detect the difference in the effects of drug (treatment) and placebo (control). DESIGN: Comparison of three scales of depression in terms of percent variance explained as indicated by the adjusted or partial eta-squared for the effect of drug versus placebo, controlling for baseline depression, in a randomized, placebo-controlled, parallel, 12-week, clinical trial of sertraline for the treatment of depression with AD. SETTING: University outpatient clinic. PARTICIPANTS: Forty-four patients with probable Alzheimer's disease and Major Depressive Episode. OUTCOME MEASURES: The Cornell Scale for Depression in Dementia (CSDD), the Hamilton Depression Rating Scale (HDRS), and the Neuropsychiatric-Inventory Mood Domains (NPI-M). RESULTS: Examination of the treatment effects as indicated by the partial eta-squared's for each scale at each wave, revealed a slight, but not significant, advantage for the use of the CSDD over the HDRS, and a significant advantage for the use of either of these over the NPI-M. Treatment effects, as reflected in the partial eta-squared's computed for the subscales at each wave, were significant for all four subscales, and were largest for the CSDD 'mood' subscale although they were not significantly greater than for the other subscales. CONCLUSIONS: The CSDD, and particularly its mood subscale, appears to be more sensitive than the HDRS, it's subscales or the NPI-M, for comparing drug to placebo in treating major depression in AD patients. Treatment effects as reflected in the partial eta-squared's were largest on the CSDD mood subscale and increased over time. The pattern for the other subscales was non-monotonic over waves and resembled the pattern for the entire scale. Perhaps combining the CSDD two subscales obscures the treatment effects for the separate subscales.

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PubMed2006

Correlates of caregiver-rated quality of life in assisted living: the Maryland Assisted Living study.

We used a cross-sectional study to examine the correlates of caregiver-rated quality of life (QOL) in 198 randomly selected residents from a stratified random sample of 22 assisted living facilities in central Maryland. We measured QOL by using the Alzheimer's Disease-Related Quality of Life Questionnaire. In general, despite cognitive impairment, residents in assisted living were rated as having a high QOL. In a multivariate regression, we found that nonmood neuropsychiatric symptoms were the strongest correlate of QOL, explaining 37% of the variance. Depressive symptoms, functional dependence, marital status, and cognition also contributed to the model, but only minimally. Because of the strong association of neuropsychiatric symptoms with QOL, special attention should be given to their recognition and amelioration.

Activities of Daily Living↗
PubMed2006

Predictors of caregiver unawareness and nontreatment of dementia among residents of assisted living facilities: the Maryland Assisted Living Study.

OBJECTIVE: Assisted living (AL) is a rapidly expanding residential option for the senior population. With increased utilization, it becomes important to understand the detection and treatment of dementia in this setting, but little is known. The objective of this study was to identify and evaluate factors associated with caregiver unawareness of dementia and failure to treat dementia in AL. METHODS: The setting was a cross-sectional study of a random sample of AL facilities in central Maryland (The Maryland Assisted Living Study). Geriatric psychiatrists evaluated 198 participants and assigned dementia diagnoses to 134 residents (67.7%). The extent to which dementia was recognized and treated in these facilities was estimated on the basis of caregiver interview and chart review data. Using logistic regression models, demographic, cognitive, and functional measures were evaluated as predictors of caregiver unawareness and nontreatment of dementia. RESULTS: Severity of cognitive and functional impairment, number of neuropsychiatric symptoms, and male gender were all independent predictors of caregiver unawareness of dementia. Family and caregiver unawareness of dementia and female gender were predictors of failure to treat dementia. Detection and treatment were not associated with race, age, or overall medical health. CONCLUSIONS: Caregivers were more likely to be unaware of dementia in residents who did not have severe cognitive impairment or obvious behavioral and functional problems. Caregiver and family unawareness were in turn associated with nontreatment. Observed gender differences in detection and treatment will require replication and further study. These observations suggest that systematic educational interventions for caregivers and families may improve detection and hence treatment in the AL setting.

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PubMed2006

Design of Depression in Alzheimer's Disease Study-2.

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.

Affect↗
PubMed2005

Transition to nursing home from assisted living is not associated with dementia or dementia-related problem behaviors.

OBJECTIVES: To examine risk factors for transition from assisted living (AL) care to skilled nursing facility (SNF) care in a random sample of adults residing in AL. DESIGN: Baseline clinical evaluation and telephone follow-up at 6-month intervals for up to 36 months. SETTING: AL facilities in central Maryland. PARTICIPANTS: There were 198 participants randomly sampled from AL facilities stratified by facility size. MEASUREMENTS: Consensus diagnoses by multidisciplinary geriatric psychiatry team as well as a broad range of neuropsychiatric and functional scales including Neuropsychiatric Inventory, Cornell Scale for Depression in Dementia, Mini-Mental State Exam, and Alzheimer's Disease Related Quality of Life Scale, as well as cognitive tests. Possible risk factors for transition to SNF were assessed in Cox proportional-hazards multivariate regression methods, using a P value less than .05 for statistical significance. RESULTS: Twenty-nine participants transitioned to SNF care. Mean AL survival time from baseline evaluation was 0.8 (SD 0.6) years for residents transitioned to SNF and 1.4 (SD 0.7) years for residents remaining in AL at follow-up. Risk factors for transition to SNF included declining health, chronic pain, appetite changes, and being widowed, while insomnia was protective against transition to SNF. Surprisingly, dementia and neuropsychiatric symptoms did not increase risk of transition to SNF. CONCLUSION: Survival time in AL is determined by factors similar to those operating on community-dwelling elderly, but dementia and neuropsychiatric symptoms do not alter survival time.

Activities of Daily Living↗
PubMed2005

Mood disorders in the medically ill: scientific review and recommendations.

OBJECTIVE: The purpose of this review is to assess the relationship between mood disorders and development, course, and associated morbidity and mortality of selected medical illnesses, review evidence for treatment, and determine needs in clinical practice and research. DATA SOURCES: Data were culled from the 2002 Depression and Bipolar Support Alliance Conference proceedings and a literature review addressing prevalence, risk factors, diagnosis, and treatment. This review also considered the experience of primary and specialty care providers, policy analysts, and patient advocates. The review and recommendations reflect the expert opinion of the authors. STUDY SELECTION/DATA EXTRACTION: Reviews of epidemiology and mechanistic studies were included, as were open-label and randomized, controlled trials on treatment of depression in patients with medical comorbidities. Data on study design, population, and results were extracted for review of evidence that includes tables of prevalence and pharmacological treatment. The effect of depression and bipolar disorder on selected medical comorbidities was assessed, and recommendations for practice, research, and policy were developed. CONCLUSIONS: A growing body of evidence suggests that biological mechanisms underlie a bidirectional link between mood disorders and many medical illnesses. In addition, there is evidence to suggest that mood disorders affect the course of medical illnesses. Further prospective studies are warranted.

Acquired Immunodeficiency Syndrome↗
PubMed2005

Physical activity, APOE genotype, and dementia risk: findings from the Cardiovascular Health Cognition Study.

Physical activity may help preserve cognitive function and decrease dementia risk, but epidemiologic findings are inconsistent. The authors conducted a prospective study to determine the association between physical activity and risk of dementia, Alzheimer's disease, and vascular dementia. The US study population comprised 3,375 men and women aged 65 years or older, free of dementia at baseline, who participated in the Cardiovascular Health Cognition Study in 1992-2000. Leisure-time energy expenditure and an activity index reflecting number of different physical activities were calculated. Analyses were based on Cox proportional hazards models. There were 480 incident cases of dementia over an average of 5.4 years of follow-up. After multivariate adjustment, participants in the highest quartile of physical energy expenditure had a relative risk of dementia of 0.85 (95% confidence interval: 0.61, 1.19) compared with those in the lowest quartile, and participants engaging in >or=4 activities had a relative risk of dementia of 0.51 (95% confidence interval: 0.33, 0.79) compared with those engaging in 0-1 activity. These associations were more marked in apolipoprotein E genotype (APOE) epsilon4 allele noncarriers but were absent in carriers. A similar pattern was observed for Alzheimer's disease and vascular dementia. Mechanisms to explain the observed relations deserve further study.

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PubMed2005

Statin use and the risk of incident dementia: the Cardiovascular Health Study.

BACKGROUND: Statins (3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors) reduce cardiovascular risk through mechanisms that might affect the development of dementia. OBJECTIVE: To evaluate whether statin use is associated with a lower risk of dementia compared with never use of lipid-lowering agents (LLAs). DESIGN: Cohort study of community-dwelling adults 65 years and older. The analysis included 2798 participants free of dementia at baseline. MAIN OUTCOME MEASURES: Using Cox proportional hazards regression analysis, we estimated the risk of incident all-cause and type-specific dementia associated with time-dependent statin therapy compared with never use of LLAs. The primary analyses incorporated a 1-year lag between exposure and outcome. Secondary analyses included the final year of exposure and modeled statin use as current use vs nonuse to simulate a case-control approach. RESULTS: Compared with never use of LLAs, ever use of statins was not associated with the risk of all-cause dementia (multivariable-adjusted hazard ratio [HR], 1.08; 95% confidence interval [CI], 0.77-1.52), Alzheimer disease alone (HR, 1.21; 95% CI, 0.76-1.91), mixed Alzheimer disease and vascular dementia (HR, 0.87; 95% CI, 0.44-1.72), or vascular dementia alone (HR, 1.36; 95% CI, 0.61-3.06). In contrast, in secondary analyses, current use of statins compared with nonuse of LLAs was associated with HRs of 0.69 (95% CI, 0.46-1.02) for all-cause dementia and 0.56 (95% CI, 0.35-0.92) for any Alzheimer disease. CONCLUSIONS: In this cohort study, statin therapy was not associated with a decreased risk of dementia. Methodological differences may explain why results of this cohort investigation differ from those of prior case-control studies. Additional investigation is needed to determine whether and for whom statin use may affect dementia risk.

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