The association of psychotropic medication use with the cognitive, functional, and neuropsychiatric trajectory of Alzheimer's disease.

OBJECTIVE: The use of psychotropic medications in Alzheimer's disease (AD) has been associated with both deleterious and potentially beneficial outcomes. We examined the longitudinal association of psychotropic medication use with cognitive, functional, and neuropsychiatric symptom (NPS) trajectories among community-ascertained incident AD cases from the Cache County Dementia Progression Study. METHODS: A total of 230 participants were followed for a mean of 3.7 years. Persistency index (PI) was calculated for all antidepressants, selective serotonin reuptake inhibitors (SSRIs), antipsychotics (atypical and typical), and benzodiazepines as the proportion of observed time of medication exposure. Mixed-effects models were used to examine the association between PI for each medication class and Mini-Mental State Exam (MMSE), Clinical Dementia Rating Sum of Boxes (CDR-Sum), and Neuropsychiatric Inventory - Total (NPI-Total) trajectories, controlling for appropriate demographic and clinical covariates. RESULTS: At baseline, psychotropic medication use was associated with greater severity of dementia and poorer medical status. Higher PI for all medication classes was associated with a more rapid decline in MMSE. For antidepressant, SSRI, benzodiazepine, and typical antipsychotic use, a higher PI was associated with a more rapid increase in CDR-Sum. For SSRIs, antipsychotics, and typical antipsychotics, a higher PI was associated with more rapid increase in NPI-Total. CONCLUSIONS: Psychotropic medication use was associated with more rapid cognitive and functional decline in AD, and not with improved NPS. Clinicians may tend to prescribe psychotropic medications to AD patients at risk of poorer outcomes, but one cannot rule out the possibility of poorer outcomes being caused by psychotropic medications.

Identification of community-residing individuals with dementia and their unmet needs for care.

BACKGROUND: Innovative approaches to the widespread delivery of evidence-based dementia care are needed. The aims of this study were to determine whether a telephone screening method could efficiently identify individuals in the community in need of care for dementia and to develop a multidimensional needs assessment tool for identifying the type and frequency of unmet needs related to memory disorders in the home setting. METHODS: This was a cross-sectional evaluation of 292 community-residing individuals aged 70 and older in Maryland. Participants were given a brief cognitive telephone screen. A subsample (n=43) received a comprehensive in-home assessment for dementia and dementia-related needs. Cognitive, functional, behavioral, and clinical factors were assessed. The Johns Hopkins Dementia Care Needs Assessment (JHDCNA) was used to identify unmet needs related to dementia. RESULTS: Telephone screening for the sample took 350 h, and 27% screened positive for dementia. Virtually all participants with dementia who received an in-home assessment had at least one unmet need, with the most frequent unmet needs being for a dementia workup, general medical care, environmental safety, assistance with ADL impairments, and access to meaningful activities. Caregivers, when present, also had a number of unmet needs, with the most common being caregiver education about dementia, knowledge of community resources, and caregiver mental health care. CONCLUSIONS: Effective and efficient means for identifying community-residing individuals with dementia are needed so that dementia care interventions can be provided to address unmet care needs of patients and their caregivers.

Effects of cardiovascular medications on rate of functional decline in Alzheimer disease.

BACKGROUND: Evidence suggests that cardiovascular medications, including statins and antihypertensive medications, may delay cognitive decline in patients with Alzheimer dementia (AD). We examined the association of cardiovascular medication use and rate of functional decline in a population-based cohort of individuals with incident AD. METHODS: In the Dementia Progression Study of the Cache County Study on Memory, Health, and Aging, 216 individuals with incident AD were identified and followed longitudinally with in-home visits for a mean of 3.0 years and 2.1 follow-up visits. The Clinical Dementia Rating (CDR) was completed at each follow-up. Medication use was inventoried during in-home visits. Generalized least-squares random-effects regression was performed with CDR Sum of Boxes (CDR-Sum) as the outcome and cardiovascular medication use as the major predictors. RESULTS: CDR-Sum increased an average of 1.69 points annually, indicating a steady decline in functioning. After adjustment for demographic variables and the baseline presence of cardiovascular conditions, use of statins (p = 0.03) and beta-blockers (p = 0.04) was associated with a slower annual rate of increase in CDR-Sum (slower rate of functional decline) of 0.75 and 0.68 points respectively, while diuretic use was associated with a faster rate of increase in CDR-Sum (p = 0.01; 0.96 points annually). Use of calcium-channel blockers, angiotensin-converting enzyme inhibitors, digoxin, or nitrates did not affect the rate of functional decline. CONCLUSIONS: In this population-based study of individuals with incident AD, use of statins and beta-blockers was associated with delay of functional decline. Further studies are needed to confirm these results and to determine whether treatment with these medications may help delay AD progression.

Vascular factors predict rate of progression in Alzheimer disease.

BACKGROUND: While there is considerable epidemiologic evidence that cardiovascular risk factors increase risk of incident Alzheimer disease (AD), few studies have examined their effect on progression after an established AD diagnosis. OBJECTIVE: To examine the effect of vascular factors, and potential age modification, on rate of progression in a longitudinal study of incident dementia. METHODS: A total of 135 individuals with incident AD, identified in a population-based sample of elderly persons in Cache County, UT, were followed with in-home visits for a mean of 3.0 years (range: 0.8 to 9.5) and 2.1 follow-up visits (range: 1 to 5). The Clinical Dementia Rating (CDR) Scale and Mini-Mental State Examination (MMSE) were administered at each visit. Baseline vascular factors were determined by interview and physical examination. Generalized least-squares random-effects regression was performed with CDR Sum of Boxes (CDR-Sum) or MMSE as the outcome, and vascular index or individual vascular factors as independent variables. RESULTS: Atrial fibrillation, systolic hypertension, and angina were associated with more rapid decline on both the CDR-Sum and MMSE, while history of coronary artery bypass graft surgery, diabetes, and antihypertensive medications were associated with a slower rate of decline. There was an age interaction such that systolic hypertension, angina, and myocardial infarction were associated with greater decline with increasing baseline age. CONCLUSION: Atrial fibrillation, hypertension, and angina were associated with a greater rate of decline and may represent modifiable risk factors for secondary prevention in Alzheimer disease. The attenuated decline for diabetes and coronary artery bypass graft surgery may be due to selective survival. Some of these effects appear to vary with age.

Dementia in hippocampal sclerosis resembles frontotemporal dementia more than Alzheimer disease.

OBJECTIVE: To characterize the clinical course of pathologically diagnosed hippocampal sclerosis dementia (HSD). BACKGROUND: Dementia associated with HSD is incompletely characterized. Previous studies suggest similarities to both Alzheimer disease (AD) and frontotemporal dementia (FTD). METHODS: Case-control analysis of the clinical course of patients with HSD, FTD, and AD from a neuropathology autopsy series conducted by a university hospital. Case histories were reviewed. Cumulative prevalence of behavioral, cognitive, psychiatric, and language symptoms were compared between groups, as was time of symptom onset. Clinical diagnostic criteria for FTD and AD were applied to case histories. Sensitivity and specificity of clinical FTD diagnostic criteria (Report of the Work Group on FTD and Pick's disease) were computed. RESULTS: Cumulative prevalence of symptoms in HSD was most similar to that of FTD and differed from AD. Behavioral abnormalities such as decreased grooming and inappropriate behavior were more prevalent in HSD and FTD than AD. Hyperorality, inappropriate behavior, and decreased interest had earlier onset in HSD and FTD. Cognitive symptoms of disorientation, dyscalculia, apraxia, and agnosia were more prevalent in AD, as were psychiatric symptoms of hallucinations, delusions, and aggression. Most HSD patients met diagnostic criteria for FTD. Criteria sensitivity was 64.0% and specificity was 73.7%. CONCLUSIONS: FTD is a clinical syndrome associated with heterogeneous neuropathology. The clinical course of HSD is more similar to that of FTD than AD. These findings, together with the neuropathologic data presented in the accompanying article, support expanding the scope of FTD (Pick complex) to include HSD.

Current concepts in mild cognitive impairment.

The field of aging and dementia is focusing on the characterization of the earliest stages of cognitive impairment. Recent research has identified a transitional state between the cognitive changes of normal aging and Alzheimer's disease (AD), known as mild cognitive impairment (MCI). Mild cognitive impairment refers to the clinical condition between normal aging and AD in which persons experience memory loss to a greater extent than one would expect for age, yet they do not meet currently accepted criteria for clinically probable AD. When these persons are observed longitudinally, they progress to clinically probable AD at a considerably accelerated rate compared with healthy age-matched individuals. Consequently, this condition has been recognized as suitable for possible therapeutic intervention, and several multicenter international treatment trials are under way. Because this is a topic of intense interest, a group of experts on aging and MCI from around the world in the fields of neurology, psychiatry, geriatrics, neuropsychology, neuroimaging, neuropathology, clinical trials, and ethics was convened to summarize the current state of the field of MCI. Participants reviewed the world scientific literature on aging and MCI and summarized the various topics with respect to available evidence on MCI. Diagnostic criteria and clinical outcomes of these subjects are available in the literature. Mild cognitive impairment is believed to be a high-risk condition for the development of clinically probable AD. Heterogeneity in the use of the term was recognized, and subclassifications were suggested. While no treatments are recommended for MCI currently, clinical trials regarding potential therapies are under way. Recommendations concerning ethical issues in the diagnosis and the management of subjects with MCI were made.

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.

MRI findings differentiate between late-onset schizophrenia and late-life mood disorder.

OBJECTIVES: Compare MRI scans of patients with late-onset schizophrenia, late-life depression and late-life bipolar disorder to age- and gender-matched controls. MRI head scans of 14 patients in each diagnostic group and 21 patients in the normal control group were compared. Subjects were recruited from inpatient and outpatient services. MEASURES: The CERAD MRI rating algorithm was used to rate degree of atrophy. RESULTS: Patients with bipolar and unipolar disorder had greater left sylvian fissure and left and right temporal sulcal enlargement, and more bilateral cortical atrophy than normals. Patients with late-onset schizophrenia had larger right temporal horns and larger third ventricles. These findings validate the distinctions between late-life affective disorder and late-onset schizophrenia and mirror changes reported in younger individuals. They may reflect underlying structural and functional abnormalities found in neuropathologic and functional imaging studies.

Randomized, placebo-controlled, double-blind clinical trial of sertraline in the treatment of depression complicating Alzheimer's disease: initial results from the Depression in Alzheimer's Disease study.

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.

The Psychogeriatric Assessment and Treatment in City Housing (PATCH) program for elders with mental illness in public housing: getting through the crack in the door.

Psychogeriatric Assessment and Treatment in City Housing (PATCH) is an outreach program targeting elderly public housing residents who need mental health care. The PATCH model relies on educating housing personnel to serve as case finders, providing in-home psychiatric evaluation and treatment, and addressing medical and social comorbidities through case management by psychiatric nurses. An examination of PATCH interventions suggests that the program's success is due to its emphasis on: (1) educating patients, housing personnel, and caregivers about patients' illnesses and need for treatment and support; and (2) coordinating care among housing staff members, patients' caregivers and their primary medical providers.

Effectiveness of a nurse-based outreach program for identifying and treating psychiatric illness in the elderly.

CONTEXT: Elderly persons with psychiatric disorders are less likely than younger adults to be diagnosed as having a mental disorder and receive needed mental health treatment. Lack of access to care is 1 possible cause of this disparity. OBJECTIVE: To determine whether a nurse-based mobile outreach program to seriously mentally ill elderly persons is more effective than usual care in diminishing levels of depression, psychiatric symptoms, and undesirable moves (eg, nursing home placement, eviction, board and care placement). DESIGN: Prospective randomized trial conducted between March 1993 and April 1996 to assess the effectiveness of the Psychogeriatric Assessment and Treatment in City Housing (PATCH) program. SETTING: Six urban public housing sites for elderly persons in Baltimore, Md. PARTICIPANTS: A total of 945 (83%) of 1195 residents in the 6 sites underwent screening for psychiatric illness. Among those screened, 342 screened positive and 603 screened negative. All screen-positive subjects aged 60 years and older (n=310) and a 10% random sample of screen-negative subjects aged 60 years and older (n=61) were selected for a structured psychiatric interview. Eleven subjects moved or died; 245 (82%) of those who screened positive and 53 (88%) of those who screened negative were evaluated to determine who had a psychiatric disorder. Data were weighted to estimate the prevalence of psychiatric disorders at the 6 sites. INTERVENTION: Among the 6 sites, residents in 3 buildings were randomized to receive the PATCH model intervention, which included educating building staff to be case finders, performing assessment in residents' apartments, and providing care when indicated; and residents in the remaining 3 buildings were randomized to receive usual care (comparison group). MAIN OUTCOME MEASURES: Number of undesirable moves and scores on the Montgomery-Asberg Depression Rating Scale (MADRS), a measure of depressive symptoms, and the Brief Psychiatric Rating Scale (BPRS), a measure of psychiatric symptoms and behavioral disorder, in intervention vs comparison sites. RESULTS: Based on weighted data, at 26 months of follow-up, psychiatric cases at the intervention sites had significantly lower (F(1)=31.18; P<.001) MADRS scores (9.1 vs 15.2) and significantly lower (F(1)=17.35; P<.001) BPRS scores (27.4 vs 33.9) than those at the nontreatment comparison sites. There was no significant difference between the groups in undesirable moves (relative risk, 0.97; 95% confidence interval, 0. 44-2.17). CONCLUSIONS: These results indicate that the PATCH intervention was more effective than usual care in reducing psychiatric symptoms in persons with psychiatric disorders and those with elevated levels of psychiatric symptoms. JAMA. 2000;283:2802-2809

Dementia in elderly persons in a general hospital.

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.

Late-onset schizophrenia and very-late-onset schizophrenia-like psychosis: an international consensus. The International Late-Onset Schizophrenia Group.

OBJECTIVE: Although schizophrenia is generally regarded as an illness with onset in late adolescence or early adult life, a sizeable minority of patients first become ill in middle or old age. Inconsistencies in diagnostic systems and nomenclature, coupled with a tendency among most schizophrenia researchers to ascribe late-onset psychoses to organic factors, have led to such cases occupying an ambiguous position in relation to schizophrenia. Through systematic review of the literature and publication of a consensus statement from an international group of experts in the field, this article aims to clarify the positions of late-onset schizophrenia and very-late-onset schizophrenia-like psychosis. METHOD: The authors conducted a MEDLINE literature review and developed a consensus statement summarizing the findings from 2 days of debate and discussion by members of the International Late-Onset Schizophrenia Group. RESULTS: The group achieved consensus on diagnosis, nomenclature, treatment guidelines, and future research directions. CONCLUSIONS: In terms of epidemiology, symptom profile, and identified pathophysiologies, the diagnoses of late-onset schizophrenia (illness onset after 40 years of age) and very-late-onset schizophrenia-like psychosis (onset after 60 years) have face validity and clinical utility. General adoption of these categories will foster systematic investigation of such patients.

Predictors of nursing home placement among elderly public housing residents.

This study examines risk factors for nursing home placement among elderly residents of public housing. Data on residents of six urban public housing developments for elderly persons (weighted n = 881) were analyzed by using logistic regression procedures to determine the predictors of nursing home placement during a 28-month period. Four baseline indicators of need were identified: greater impairment in instrumental activities of daily living, cognitive disorder, high scores on the General Health Questionnaire, and psychotic disorder. Thus, functional status and mental morbidity are major contributors to nursing home placement in this setting.

Depression without sadness: alternative presentations of depression in late life.

Older adults often deny feeling sad while exhibiting other characteristics of depression. Elderly patients with depression who do not present with sadness often have unexplained somatic complaints and exhibit a sense of hopelessness. Anxiety and anhedonia (a general loss of ability to feel pleasure) are also encountered frequently. Other features that may indicate underlying depression include slowness of movement and lack of interest in personal care. A screening device, such as the Center for Epidemiologic Studies--Depression Scale, Revised (CES-D-R), may identify depression in suspicious cases. When this condition is identified, treatment should generally include the use of an antidepressant medication, usually a selective serotonin reuptake inhibitor.

Sadness in older persons: 13-year follow-up of a community sample in Baltimore, Maryland.

BACKGROUND: Our prior psychometric work suggested that older adults interviewed in 1981 in a community survey were less likely than younger adults to report dysphoria. We hypothesized that this would also be true of older adults interviewed 13 years later. METHODS: This study is a population-based 13-year follow-up survey of community-dwelling adults living in East Baltimore in 1981. Subjects were the continuing participants of the Baltimore Epidemiologic Catchment Area Program. After excluding 269 adults who were 65 years of age and older at initial interview in 1981, 1651 adults remained (347 aged 65 years and older and 1304 who were 30-64 years-old at follow-up). We applied structural equations with a measurement model for dichotomous data (the MIMIC -- multiple indicators, multiple causes -- model) to compare symptoms between adults who were 65 years and older at follow-up with younger adults, in relation to the nine symptom groups comprising the diagnostic criteria for major depression, adjusting for several potentially influential characteristics (namely, gender, self-reported ethnicity, educational attainment, cognitive impairment, marital status and employment). RESULTS: Older adults were less likely to endorse sadness as evidenced by a direct effect coefficient of -0.335 (95% Confidence Interval -0.643, -0.027). After adjusting for several potentially influential characteristics, the direct effect of age was substantially unchanged (-0.298 (95% CI -0.602, 0.006)). CONCLUSIONS: Older adults in 1994, like older adults in 1981, were less likely to endorse sadness than younger persons. This finding suggests, but does not prove, that the observed age difference in reporting depression does not reflect a cohort effect.