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Objective: Citalopram has been shown to improve agitation in patients with Alzheimer's disease. The authors evaluated whether other neuropsychiatric symptoms improve with citalopram treatment compared with placebo., Method: In this planned secondary analysis of the Citalopram for Agitation in Alzheimer's Disease study, the authors evaluated the effect of citalopram on the 12 neuropsychiatric symptom domains assessed by the Neuropsychiatric Inventory (NPI). They compared caregiver-reported NPI scores at week 9 in patients receiving citalopram (30 mg/day) or placebo with regard to both the presence or absence of individual neuropsychiatric symptoms and individual domain scores (reflecting severity) in participants who had symptoms at week 9., Results: At week 9, participants treated with citalopram were significantly less likely to be reported as showing delusions (odds ratio=0.40), anxiety (odds ratio=0.43), and irritability/lability (odds ratio=0.38). A comparison of median scores of participants with symptoms present at week 9 showed significant differences favoring citalopram for hallucinations and favoring placebo for sleep/nighttime behavior disorders., Conclusions: While dosage constraints must be considered because of citalopram's adverse effect profile, this agent's overall therapeutic effects in patients with Alzheimer's disease and agitation, in addition to efficacy for agitation/aggression, included reductions in the frequency of irritability, anxiety, and delusions; among patients who had these symptoms at week 9, they included a reduction in the severity of hallucinations but an increase in the severity of sleep/nighttime behavior disorders.

Objective: Pharmacological treatments for agitation and aggression in patients with Alzheimer's disease have shown limited efficacy. The authors assessed the heterogeneity of response to citalopram in the Citalopram for Agitation in Alzheimer Disease (CitAD) study to identify individuals who may be helped or harmed., Method: In this double-blind parallel-group multicenter trial of 186 patients with Alzheimer's disease and clinically significant agitation, participants were randomly assigned to receive citalopram or placebo for 9 weeks, with the dosage titrated to 30 mg/day over the first 3 weeks. Five planned potential predictors of treatment outcome were assessed, along with six additional predictors. The authors then used a two-stage multivariate method to select the most likely predictors; grouped participants into 10 subgroups by their index scores; and estimated the citalopram treatment effect for each., Results: Five covariates were likely predictors, and treatment effect was heterogeneous across the subgroups. Patients for whom citalopram was more effective were more likely to be outpatients, have the least cognitive impairment, have moderate agitation, and be within the middle age range (76-82 years). Patients for whom placebo was more effective were more likely to be in long-term care, have more severe cognitive impairment, have more severe agitation, and be treated with lorazepam., Conclusions: Considering several covariates together allowed the identification of responders. Those with moderate agitation and with lower levels of cognitive impairment were more likely to benefit from citalopram, and those with more severe agitation and greater cognitive impairment were at greater risk for adverse responses. Considering the dosages used and the association of citalopram with cardiac QT prolongation, use of this agent to treat agitation may be limited to a subgroup of people with dementia.

Objective: Little is known about factors influencing the rate of progression of Alzheimer's dementia. Using data from the Cache County Dementia Progression Study, the authors examined the link between clinically significant neuropsychiatric symptoms in mild Alzheimer's dementia and progression to severe dementia or death., Method: The Cache County Dementia Progression Study is a longitudinal study of dementia progression in incident cases of this condition. Survival analyses included unadjusted Kaplan-Meier plots and multivariate Cox proportional hazard models. Hazard ratio estimates controlled for age at dementia onset, dementia duration at baseline, gender, education level, General Medical Health Rating, and apolipoprotein E epsilon 4 genotype., Results: Three hundred thirty-five patients with incident Alzheimer's dementia were studied. Sixty-eight (20%) developed severe dementia over the follow-up period. Psychosis (hazard ratio=2.007), agitation/aggression (hazard ratio=2.946), and any one clinically significant neuropsychiatric symptom (domain score ≥4, hazard ratio=2.682) were associated with more rapid progression to severe dementia. Psychosis (hazard ratio=1.537), affective symptoms (hazard ratio=1.510), agitation/aggression (hazard ratio=1.942), mildly symptomatic neuropsychiatric symptoms (domain score of 1-3, hazard ratio=1.448), and clinically significant neuropsychiatric symptoms (hazard ratio=1.951) were associated with earlier death., Conclusions: Specific neuropsychiatric symptoms are associated with shorter survival time from mild Alzheimer's dementia to severe dementia and/or death. The treatment of specific neuropsychiatric symptoms in mild Alzheimer's dementia should be examined for its potential to delay time to severe dementia or death.

Objective: Public health campaigns encouraging early help seeking have increased rates of mild cognitive impairment (MCI) diagnosis in Western countries, but we know little about how to treat or predict dementia outcomes in persons with the condition., Method: The authors searched electronic databases and references for longitudinal studies reporting potentially modifiable risk factors for incident dementia after MCI. Two authors independently evaluated study quality using a checklist. Meta-analyses were conducted of three or more studies., Results: There were 76 eligible articles. Diabetes and prediabetes increased risk of conversion from amnestic MCI to Alzheimer's dementia; risk in treated versus untreated diabetes was lower in one study. Diabetes was also associated with increased risk of conversion from any-type or nonamnestic MCI to all-cause dementia. Metabolic syndrome and prediabetes predicted all-cause dementia in people with amnestic and any-type MCI, respectively. Mediterranean diet decreased the risk of conversion to Alzheimer's dementia. The presence of neuropsychiatric symptoms or lower serum folate levels predicted conversion from any-type MCI to all-cause dementia, but less formal education did not. Depressive symptoms predicted conversion from any-type MCI to all-cause dementia in epidemiological but not clinical studies., Conclusions: Diabetes increased the risk of conversion to dementia. Other prognostic factors that are potentially manageable are prediabetes and the metabolic syndrome, neuropsychiatric symptoms, and low dietary folate. Dietary interventions and interventions to reduce neuropsychiatric symptoms, including depression, that increase risk of conversion to dementia may decrease new incidence of dementia.

Neuropsychiatric symptoms such as agitation and delusions occur commonly in elderly patients with dementia and often cause significant distress. Data on treatment efficacy are strongest for atypical antipsychotics, but these agents must be used with great caution. Adverse effects in patients with dementia include an increased risk of mortality and cerebrovascular events, as well as metabolic effects, extrapyramidal symptoms, falls, cognitive worsening, cardiac arrhythmia, and pneumonia. Conventional antipsychotics may pose an even greater safety risk. No clear efficacy evidence exists to support the use of alternative psychotropic classes (e.g., antidepressants, anticonvulsants), although they may be safer options. An antipsychotic trial is warranted when nonpharmacological intervention is unsuccessful and neuropsychiatric symptoms or associated behaviors cause severe distress or pose a significant safety risk. Before an atypical antipsychotic is started, a comprehensive assessment should be performed to rule out medical causes of the neuropsychiatric symptoms and to ascertain whether any contributing environmental or caregiver factors are present. Risks, benefits, and alternatives should be discussed with the patient and surrogate decision maker, with an opportunity given to ask questions. Dosages should be the lowest necessary, and metabolic parameters should be regularly monitored. Face-to-face visits are important to monitor response, tolerance, and the need for continued treatment. For patients in whom neuropsychiatric symptoms have been much improved or have been in remission for 3-6 months, a discontinuation trial should be considered. Through careful selection of appropriate patients for treatment, education of patients and caregivers, and close monitoring, safety risks can be minimized.

Objective: The impact of the atypical antipsychotics olanzapine, quetiapine, and risperidone on cognition in patients with Alzheimer's disease is unclear. The authors assessed the effects of time and treatment on neuropsychological functioning during the Clinical Antipsychotic Trials of Intervention Effectiveness-Alzheimer's Disease study (CATIE-AD)., Method: CATIE-AD included 421 outpatients with Alzheimer's disease and psychosis or agitated/aggressive behavior who were randomly assigned to receive masked, flexible-dose olanzapine, quetiapine, risperidone, or placebo. Based on their clinicians' judgment, patients could discontinue the originally assigned medication and receive another randomly assigned medication. Patients were followed for 36 weeks, and cognitive assessments were obtained at baseline and at 12, 24, and 36 weeks. Outcomes were compared for 357 patients for whom data were available for at least one cognitive measure at baseline and one follow-up assessment that took place after they had been on their prescribed medication or placebo for at least 2 weeks., Results: Overall, patients showed steady, significant declines over time in most cognitive areas, including in scores on the Mini-Mental State Examination (MMSE; -2.4 points over 36 weeks) and the cognitive subscale of the Alzheimer's Disease Assessment Scale (-4.4 points). Cognitive function declined more in patients receiving antipsychotics than in those given placebo on multiple cognitive measures, including the MMSE, the cognitive subscale of the Brief Psychiatric Rating Scale, and a cognitive summary score summarizing change on 18 cognitive tests., Conclusions: In CATIE-AD, atypical antipsychotics were associated with worsening cognitive function at a magnitude consistent with 1 year's deterioration compared with placebo. Further cognitive impairment is an additional risk of treatment with atypical antipsychotics that should be considered when treating patients with Alzheimer's disease.

Objective: The second-generation antipsychotics are associated with metabolic abnormalities in patients with schizophrenia. Elderly patients with Alzheimer's disease are frequently treated with these antipsychotics, but limited data are available on their metabolic effects., Method: The authors assessed 186 male and 235 female Alzheimer's disease outpatients from the Clinical Antipsychotic Trials of Intervention Effectiveness-Alzheimer's Disease (CATIE-AD) for changes in weight, waist circumference, blood pressure, fasting glucose, and lipids in relation to duration of second-generation antipsychotic use (i.e., olanzapine, quetiapine, and risperidone) throughout the 36-week trial, using logistic regression and mixed-effects models., Results: Women showed significant weight gain (0.14 lb/week of use) while change was nonsignificant in men. Clinically significant weight gain (i.e., > or = 7% of body weight) was seen among patients with antipsychotic use < or = 12 weeks (odds ratio [OR]=1.56, 95% CI=0.53 to 4.58), between 12 and 24 weeks (OR=2.89, 95% CI=0.97 to 8.64), and > 24 weeks (OR=3.38, 95% CI=1.24 to 9.23) relative to patients who did not use antipsychotics during the trial. Olanzapine and quetiapine treatments were significantly associated with weight gain (0.12 and 0.14 lb/week, respectively). In addition, olanzapine was significantly associated with decreases in HDL cholesterol (-0.19 mg/dl/week) and increased girth (0.07 inches/week) relative to the placebo group. No treatment effects were noted for changes in blood pressure, glucose, and triglycerides., Conclusion: Second-generation antipsychotic use was associated with weight gain in women, with olanzapine and quetiapine in particular, and with unfavorable change in HDL cholesterol and girth with olanzapine. The potential consequences of these effects suggest that patients with Alzheimer's disease treated with second-generation antipsychotics should be monitored closely.

Objective: The study measured the effects of atypical antipsychotics on psychiatric and behavioral symptoms in patients with Alzheimer's disease and psychosis or agitated behavior., Method: The Clinical Antipsychotic Trials of Intervention Effectiveness-Alzheimer's Disease (CATIE-AD) Alzheimer's disease effectiveness study included 421 outpatients with Alzheimer's disease and psychosis or agitated/aggressive behavior. Patients were assigned randomly to masked, flexible-dose treatment with olanzapine, quetiapine, risperidone, or placebo for up to 36 weeks. Patients could be randomly reassigned to a different medication at the clinician's discretion, which ended phase 1. Psychiatric and behavioral symptoms, functioning, cognition, care needs, and quality of life were measured at regular intervals., Results: In relation to placebo, the last observation in phase 1 showed greater improvement with olanzapine or risperidone on the Neuropsychiatric Inventory total score, risperidone on the Clinical Global Impression of Changes, olanzapine and risperidone on the Brief Psychiatric Rating Scale (BPRS) hostile suspiciousness factor, and risperidone on the BPRS psychosis factor. There was worsening with olanzapine on the BPRS withdrawn depression factor. Among patients continuing phase 1 treatment at 12 weeks, there were no significant differences between antipsychotics and placebo on cognition, functioning, care needs, or quality of life, except for worsened functioning with olanzapine compared to placebo., Conclusion: In this descriptive analysis of outpatients with Alzheimer's disease in usual care settings, some clinical symptoms improved with atypical antipsychotics. Antipsychotics may be more effective for particular symptoms, such as anger, aggression, and paranoid ideas. They do not appear to improve functioning, care needs, or quality of life.

Objective: The authors systematically reviewed the literature on psychological approaches to treating the neuropsychiatric symptoms of dementia., Method: Reports of studies that examined effects of any therapy derived from a psychological approach that satisfied prespecified criteria were reviewed. Data were extracted, the quality of each study was rated, and an overall rating was given to each study by using the Oxford Centre for Evidence-Based Medicine criteria., Results: A total of 1,632 studies were identified, and 162 satisfied the inclusion criteria for the review. Specific types of psychoeducation for caregivers about managing neuropsychiatric symptoms were effective treatments whose benefits lasted for months, but other caregiver interventions were not. Behavioral management techniques that are centered on individual patients' behavior or on caregiver behavior had similar benefits, as did cognitive stimulation. Music therapy and Snoezelen, and possibly sensory stimulation, were useful during the treatment session but had no longer-term effects; interventions that changed the visual environment looked promising, but more research is needed., Conclusions: Only behavior management therapies, specific types of caregiver and residential care staff education, and possibly cognitive stimulation appear to have lasting effectiveness for the management of dementia-associated neuropsychiatric symptoms. Lack of evidence regarding other therapies is not evidence of lack of efficacy. Conclusions are limited because of the paucity of high-quality research (only nine level-1 studies were identified). More high-quality investigation is needed.

Objective: The authors' goal was to investigate the relationship between depression and HIV risk behaviors or sexually transmitted disease (STD) diagnosis at an urban STD clinic., Method: Using audio computer-assisted self-interview, 671 STD clinic patients answered questions about HIV risk behaviors and depression in a large-scale, cross-sectional study. A subset of the patients (N=201) was evaluated for current major depressive disorder by interviewers using the nonpatient edition of the Structured Clinical Interview for DSM-IV., Results: Depressed patients were more likely to have sex for money or drugs, to have had sex with an intravenous drug user, to have sex when "high" on alcohol or drugs, to have a greater number of lifetime sex partners, and to abuse alcohol or drugs than were nondepressed patients. Associations of HIV risk behaviors with depression persisted after adjustment for substance abuse., Conclusions: Depression in STD clinic patients is associated with HIV risk behaviors but not STD diagnosis. Identifying depression and developing strategies to intervene effectively may reduce HIV risk behaviors and improve health outcomes.

Objective: This study estimated the psychiatric morbidity of patients with degenerative cerebellar diseases., Method: The study included a series of 31 patients with degenerative cerebellar diseases, compared with 21 patients with Huntington's disease and 29 neurologically healthy comparison subjects. Comprehensive psychiatric evaluations, including the Structured Clinical Interview for DSM-IV and psychopathology rating scales, were administered., Results: The overall rate of noncognitive psychiatric disorders was 77% in the patients with degenerative cerebellar diseases, nearly identical to that in the patients with Huntington's disease (81%) and about double that seen in the neurologically healthy subjects (41%). There were high rates of all mood disorders in both the degenerative cerebellar diseases group (68%) and the Huntington's disease group (43%); the rate in the degenerative cerebellar diseases group was significantly higher than that in the neurologically healthy subjects (31%). The frequency of personality change in the three groups was striking: change was present in 26% of the degenerative cerebellar diseases patients, 48% of the Huntington's disease patients, and none of the neurologically healthy comparison subjects. A total of 19% of the degenerative cerebellar diseases subjects and 71% of the Huntington's disease subjects met DSM-IV criteria for either cognitive disorder or dementia., Conclusions: The high rate of psychiatric and cognitive disorders in the patients with degenerative cerebellar diseases suggests that many, if not most, patients with degenerative cerebellar diseases may benefit from psychiatric interventions. These results also support previous findings that the cerebellum may have a role in modulating emotion and cognition.

Objective: This study assessed HIV risk behaviors and their association with psychiatric disorders among women prisoners., Methods: HIV risk behaviors practiced in the five years before incarceration were ascertained with the Risk Behavior Assessment interview for 177 inmates at the Maryland Correctional Institution for Women. The Structured Clinical Interview for the DSM-IV was used to determine the occurrence of posttraumatic stress disorder (PTSD), major depression, and dysthymic disorder among the women. Regression models were used to determine the association between HIV risk behavior and psychiatric disorders., Results: HIV risk behaviors in the five years before incarceration included never or rarely having used condoms (56 percent of the women), injection drug use (42 percent), sexual intercourse with a partner who used injection drugs (42 percent), prostitution (30 percent), needle sharing (30 percent), receptive anal sex (19 percent), and having more than 100 sex partners (7 percent). After the analysis adjusted for age, education, race, HIV status, and addictive disorders, a lifetime occurrence of PTSD was associated with the practice of anal sex (odds ratio=1.7; 95 percent confidence interval=1.26 to 2.16; p<.02) and prostitution (OR=1.56; 95% CI=1.17 to 1.95; p<.03)., Conclusions: HIV risk behaviors before incarceration were highly prevalent among the women in this study. Rates of PTSD, depression, and dysthymic disorder were also high. PTSD was associated with prostitution and receptive anal sex, and the disorder may contribute to high rates of risky sexual behavior. Targeted HIV risk reduction efforts among women prisoners should include evaluation for PTSD; conversely, women prisoners with a diagnosis of PTSD should be evaluated for prior HIV sexual risk behaviors.

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.

Objective: The authors report findings from a study of 5,092 community residents who constituted 90% of the elderly resident population of Cache County, Utah., Method: The 5,092 participants, who were 65 years old or older, were screened for dementia. Based on the results of this screen, 1,002 participants (329 with dementia and 673 without dementia) underwent comprehensive neuropsychiatric examinations and were rated on the Neuropsychiatric Inventory, a widely used method for ascertainment and classification of dementia-associated mental and behavioral disturbances., Results: Of the 329 participants with dementia, 214 (65%) had Alzheimer's disease, 62 (19%) had vascular dementia, and 53 (16%) had another DSM-IV dementia diagnosis; 201 (61%) had exhibited one or more mental or behavioral disturbances in the past month. Apathy (27%), depression (24%), and agitation/aggression (24%) were the most common in participants with dementia. These disturbances were almost four times more common in participants with dementia than in those without. Only modest differences were observed in the prevalence of mental or behavioral disturbances in different types of dementia or at different stages of illness: participants with Alzheimer's disease were more likely to have delusions and less likely to have depression. Agitation/aggression and aberrant motor behavior were more common in participants with advanced dementia., Conclusions: On the basis of their findings in this large community population of elderly people, the authors conclude that a wide range of dementia-associated mental and behavioral disturbances afflict the majority of individuals with dementia. Because of their frequency and their adverse effects on patients and their caregivers, these disturbances should be ascertained and treated in all cases of dementia.

Objective: This study investigated the prevalence of dementia in a general hospital, reasons for which patients with dementia were admitted, and the relationship between dementia and length of stay, cost, and in-hospital mortality rate., Method: The study focused on data from the hospital database on 21,251 patients aged 60 and older who were discharged in 1996 and 1997. Patients were grouped as with or without a discharge diagnosis of dementia by ICD-9-CM criteria. The groups were compared on sociodemographic characteristics, principal discharge diagnoses, lengths of stay, costs, and in-hospital mortality rates., Results: The prevalence of dementia among discharged patients was 3.9% (N=823); it was dependent on age (age 60-64, prevalence=2.6%; age 85 and older, prevalence=8.9%). The primary discharge diagnoses of the groups were different. The mean length of stay was 10.4 days for patients with dementia and 6.5 days for patients without dementia. Per capita hospital costs were $4,000 higher for patients with dementia. Differences in lengths of stay and per capita costs were statistically significant after adjusting for age, race, and sex. Lengths of stay and hospital costs for patients with dementia were significantly higher for eight primary discharge diagnoses after adjusting for age, race, and sex., Conclusions: Dementia is present in a significant proportion of patients admitted to general inpatient units. Patients with dementia are admitted for different reasons than patients without dementia and appear to have longer stays, which are associated with higher costs. Efforts to identify dementia early during hospitalization could improve patient care and reduce costs.

Objective: The goal of this study was to determine the frequency of physically aggressive behavior in community-residing patients with dementia and its relationship to depression., Method: A consecutive series of 541 patients with DSM-IV-defined dementia underwent comprehensive neuropsychiatric evaluation and were rated on the Cornell Scale for Depression in Dementia, the Mini-Mental State, the Psychogeriatric Dependency Rating Scale, and the General Medical Health Rating., Results: Physically aggressive behavior was exhibited by 79 patients in the 2 weeks before evaluation. Aggressive behavior was closely associated with moderate to severe depression, male gender, and greater impairment in activities of daily living, even after adjustment for delusions, hallucinations, sleep disturbance, and severity of cognitive impairment. After adjustment for depression, gender, and impairment in activities of daily living, there was no association between physically aggressive behavior and the presence of either delusions or hallucinations., Conclusions: A substantial minority of patients with dementia exhibit physically aggressive behavior, and this aggression is strongly linked with the presence of depressive symptoms. It is possible that the identification and treatment of depression in dementia may be a means of preventing and managing physically aggressive behavior.

Objective: The epidemiology of cognitive decline over 11.5 years was investigated in a large community-residing population, with a special emphasis on the relationship between education and cognitive decline., Method: The study was an 11.5-year follow-up of a probability sample of the adult household residents of east Baltimore. From the Baltimore cohort of the Epidemiologic Catchment Area study, 1,488 participants completed the Mini-Mental State during three study waves in 1981, 1982, and 1993-1996. For each study participant, the difference in scores on the Mini-Mental State between waves 2 and 3 was calculated., Results: Over a median interval of 11.5 years, the study participants' scores on the Mini-Mental State declined a mean of 1.41 points, and the scores of 68% of the participants declined by at least 1 Mini-Mental State point. With and without adjustment for age, greater declines were associated with having 8 years or less of formal education and with being African American., Conclusions: Over a long time period, cognitive decline occurred in all age groups. Having more than 8 years of formal education was associated with less decline. However, beyond 9 years, additional education was not associated with a further reduction in cognitive decline. This suggests that a minimal amount of education during early critical periods might confer protection against cognitive decline later in life.

Objective: The authors sought to determine whether rates of depressive symptoms change from early- to late-stage HIV-1 infection and to determine the predictors of depressive symptoms as AIDS develops., Method: The data for this study were from 911 HIV-seropositive men-community volunteers from four U.S. cities-who entered the 10-year Multicenter AIDS Cohort Study without a diagnosis of AIDS and subsequently developed AIDS. The subjects underwent semiannual follow-ups during the study period. The outcome measures-overall depressive symptoms, nonsomatic depressive symptoms, syndromal depression, and severe depression-were assessed over the 5 years before and the 2 years after AIDS diagnosis from responses on the Center for Epidemiologic Studies Depression Scale (CES-D Scale)., Results: Depressive symptoms were stable over time from month 60 to month 18 before AIDS developed. However, beginning 12-18 months before AIDS diagnosis, there was a significant rise in all measures of depression, which reached a plateau within 6 months before AIDS developed. At this plateau, there was a 45% increase in mean CES-D Scale scores above baseline. An elevated CES-D Scale score in the earlier stages of infection, a self-report of AIDS-related symptoms (such as rash and lymphadenopathy), concurrent unemployment, cigarette smoking, and limited social supports were consistent predictors of higher rates of depression as AIDS developed., Conclusions: There is a dramatic, sustained rise in depressive symptoms as AIDS develops, beginning as early as 18 months before clinical AIDS is diagnosed. Prior depression, HIV-disease-related factors, and psychological stressors contribute to this rise. This robust phenomenon invites further characterization.

In a chart review at a hospital's infectious disease AIDS clinic, manic syndromes affected 8% of patients who had AIDS. Of the 14 patients with manic episodes, those without a family or personal history of mood disorder presented later in the course of HIV infection and had a higher prevalence of comorbid dementia.