Factors related to medication adherence in memory disorder clinic patients.

Medication adherence is a substantial problem in the elderly. It may be even more important among elderly persons with memory problems, since other factors that lead to non-adherence may be compounded with the memory problems themselves. The objective was to determine whether a model that integrates research on medication adherence from several research domains is useful in understanding adherence in elderly patients. The methodology involved a cross-sectional observational study using a convenience sample of 63 patients drawn from a university-affiliated outpatient memory disorders clinic. The primary measure of medication adherence was caregivers' reports of patients' medication adherence. Patients and their caregivers were asked questions assessing their beliefs about the seriousness of each condition for which a medication was prescribed and the likely outcome of that condition without treatment. Additional data collected included presence of side effects, total number of medications taken, and patients' mood and cognitive status. Multilevel path analysis confirmed several model-based predictions. Caregivers' reports of adherence were predicted by estimates of disease outcome, the presence of side effects, and patients' relying on themselves to remember to take medications. Results partially confirm the integrative model in understanding medication adherence in these patients. Patients' beliefs about the likely effect of medication treatment for their condition and the presence of side effects influence reported medication adherence. Results thus suggest that efforts to educate patients about the likely response of their medical condition to treatment and to assess and deal with medication side effects might improve patient adherence.

Factor structure of the Cornell Scale for Depression in Dementia for Anglo and Hispanic patients with dementia.

The authors assessed the equivalence of the factor structure of the Cornell Scale for Depression in Dementia (CSDD) in samples of Anglo and Hispanic patients with Alzheimer's disease (AD). Comparing the factor structure of the CSDD in these groups helps establish its validity and aids in its clinical interpretation with Hispanic patients. CSDD ratings were first subjected to preliminary exploratory factor analyses; then the factor structure of the CSDD across groups of English- and Spanish-speaking patients was tested using structural equation modeling. Analyses showed overall similarity in the CSDD factor structure for the two groups but also revealed differences in factor content for several items. The authors discuss the relevance of these differences for those using the CSDD with Hispanic AD patients.

An evaluation of the NINCDS-ADRDA neuropsychological criteria for the assessment of Alzheimer's disease: a confirmatory factor analysis of single versus multi-factor models.

Neuropsychological test batteries are frequently used to assess the nature and severity of cognitive deficits among patients with early Alzheimer's Disease (AD) and related disorders. The NINCDS-ADRDA criteria are among the most widely used guidelines to diagnose dementia (McKhann et al.,1984). These criteria specify eight distinct areas of neuropsychological function that should be evaluated in patients with suspected cognitive impairment. Recent studies have suggested that neuropsychological deficits observed in AD may be explained by a single general factor related to memory deficits or to executive dysfunction. In contrast, the results of other investigations have indicated that multiple qualitatively different factors underlie cognitive abilities in AD. In the present study, we used confirmatory factor analysis to examine the structure of cognitive abilities in AD and to assess the extent to which single and multiple ability factors accurately represent neuropsychological test data obtained from patients with AD. Results indicated that the NINCDS-ADRDA model fit the data better than a single factor model. However, a more parsimonious model specifying memory, verbal abilities, visuospatial skills, executive function, and higher as well as lower functional activities of daily living fit the data better than the NINCDS-ADRDA model. These results have important theoretical and practical implications for diagnostic evaluation.

The Behavior Problems Checklist-Spanish: a preliminary study of a new scale for the assessment of depressive symptoms and disruptive behaviors in Hispanic patients with dementia.

Few instruments are available with which to measure behavioral and psychological signs and symptoms in Hispanic patients with dementia. Therefore, the aim of the current study was to develop and evaluate a 17-item scale adapted from the Revised Memory and Behavior Problems Checklist. This measure, the Behavior Problems Checklist-Spanish (BPC-S), assesses caregiver-reported symptoms of depression and disruption in patients with dementia. The sample for this study comprised 27 Spanish-speaking Hispanic patients and their family caregivers evaluated at a university-affiliated memory disorders center. All patients met diagnostic criteria for possible or probable Alzheimer's disease as set forth by the National Institute of Neurological and Communicative Diseases and Stroke-Alzheimer's Disease and Related Disorders Association. Satisfactory convergent validity, discriminant validity, and internal consistency reliability were demonstrated for the Depression and Disruption subscales of the BPC-S. Both of these neuropsychiatric disturbances were related to heightened levels of caregiver burden. The results of this preliminary study suggest the BPC-S is a brief, psychometrically sound caregiver-report instrument to assess symptoms of mood disturbance and behavioral disruption in Hispanic patients with dementia. This instrument may have utility for both clinical and research purposes.

Ethnicity and dementia.

A large number of studies have examined both the epidemiology and neuropsychiatric manifestations of dementia among older adults. However, there is a relative dearth of studies focusing on ethnic minority elders in the United States. This article reviews the existing empiric literature in the area of ethnicity and dementia. For the purpose of this paper, the focus will be on Hispanics and black Americans, the two most prevalent ethnic minority populations in the United States. This review includes discussion of terminology issues, diagnosis, epidemiology, and clinical features, in addition to caregiver issues.

Clinical characteristics of community-dwelling black Alzheimer's disease patients.

There is a relative dearth of studies examining the cognitive and neuropsychiatric features of black Alzheimer's disease (AD) patients in the United States. Therefore, this cross-sectional investigation reported on the prevalence and clinical correlates of depression and psychosis in a community-dwelling black AD sample. The study participants comprised 55 English-speaking black patients evaluated consecutively at a university-affiliated memory disorders clinic. All patients were evaluated utilizing standardized procedures and diagnosed with possible or probable AD according to the criteria established by the National Institute of Neurological and Communicative Diseases and Stroke-Alzheimer's Disease and Related Disorders Association. The presence of neuropsychiatric symptoms, including major depression and psychosis (delusions or hallucinations) was established via a semistructured psychiatric interview with the patient and primary care giver. The level of global cognitive impairment was rated with the Mini-Mental State Examination. The results showed that major depression and psychosis were observed in 20% and 58% of the sample, respectively. Mood disturbance was linked with low education, whereas psychosis was associated with greater cognitive dysfunction. This study provides important insight into the clinical characteristics of community-dwelling black AD patients. It is clear that continued research in the area of ethnicity and dementia is warranted to better understand the clinical needs of blacks and other minority populations in the United States that are afflicted with AD.

Family history of dementia and current depression in nondemented community-dwelling older adults.

Since it has been postulated that mood disturbance in nondemented older adults may represent a prodromal feature of dementia for a subgroup of patients, it would be expected that patients with these symptoms would evidence a greater prevalence of family history of dementia. In a sample of 3225 community-dwelling cognitively intact elderly recruited from a free memory-screening program, we found that current depression was more common in participants with a positive versus a negative family history of dementia in first-degree relatives (17% versus 11%; Fisher's Exact Test, P < .0001). This relationship remained significant after controlling for age, education, gender, ethnicity, and Folstein Mini-Mental State Examination score (OR = 1.5; 95% CI = 1.2-1.9, Wald X2 = 15.5, P < .001). The results suggest that symptoms of depression may herald the onset of an incipient dementia syndrome in a subset of geriatric patients. Alternatively, the results may be indicative of familial aggregation of dementia and depression.

Predictors of positive and negative appraisal among Cuban American caregivers of Alzheimer's disease patients.

OBJECTIVE: This study investigated predictors of positive (satisfaction) and negative (burden) appraisal among Cuban American (CA) caregivers of Alzheimer's disease (AD) patients. DESIGN: Cross-sectional study of AD patients and their family caregivers. SETTING: A university-affiliated outpatient memory disorders clinic. SUBJECTS: A convenience sample of 40 CA family caregivers of patients diagnosed with probable or possible AD according to NINCDS-ADRDA diagnostic criteria. MEASURES: AD patients: Mini-Mental State Examination (MMSE), Blessed Dementia Scale (BDS) and the Behavioral Pathology in Alzheimer's Disease Rating Scale (BEHAVE-AD). Caregivers: Caregiving Burden Scale (CBS), Caregiving Satisfaction Scale (CSS), Perceived Emotional Support scale (PES) and the Short Form-36 Health Survey-General Health Index (GH). RESULTS: Appraised burden was predicted by increased patient behavioral pathology, female caregiver gender and lower levels of perceived emotional support. The association between older caregiver age and increased burden approached significance. Older caregiver age and higher levels of perceived social support were shown to predict appraised satisfaction. Post-hoc analyses also indicated that length of residence in the United States, a measure of acculturation, was not associated with positive or negative appraisal. CONCLUSION: Appraised burden and satisfaction represent important outcomes of dementia care that show relations with distinct factors among CA caregivers. It is clear that further research is warranted in order to ascertain the relationship of ethnicity or culture to the process and psychological consequences of dementia caregiving. Continued investigations into predictors of caregiving satisfaction are also recommended.

Relationship of behavioral and psychological symptoms to cognitive impairment and functional status in Alzheimer's disease.

OBJECTIVE: This cross-sectional study examined the relationship of behavioral and psychological symptoms to cognitive and functional impairment in Alzheimer's disease (AD). DESIGN: One hundred and fourteen patients were evaluated consecutively at a university-affiliated outpatient memory disorders clinic and diagnosed with possible or probable Alzheimer's disease (AD) according to NINCDS-ADRDA criteria. Subjects were assessed with the Behavioral Pathology in Alzheimer's Disease Scale (BEHAVE-AD), Revised Memory and Behavior Problem Checklist (RMBPC), Blessed Dementia Scale (BDS), and Mini-Mental State Examination (MMSE). RESULTS: Several symptoms of behavioral pathology showed associations with MMSE scores, including activity disturbances, delusions, and hallucinations. After controlling for the variance associated with the MMSE, activity disturbances, diurnal disturbances, delusions, and hallucinations were linked with BDS scores. CONCLUSIONS: The results suggest that some non-cognitive symptoms may be related to the neurobiologic mechanisms underlying the increased cognitive dysfunction in AD. Specific symptoms of behavioral pathology may also impact a patient's ability to perform important self-maintenance behaviors.

Depressive symptoms in Alzheimer's disease. An examination among community-dwelling Cuban American patients.

The authors examined the prevalence and clinical correlates of mood disturbance in 96 Cuban American (CA) Alzheimer's disease (AD) patients. Depression (Cornell Scale for Depression in Dementia score > or = 7) was evident in 39.6% of the participants and showed associations with comorbid psychosis, lower education, and decreased length of residence in the United States, a measure of acculturation. Mood disturbance was not related to age, gender, marital status, cognitive dysfunction, functional impairment, history of significant alcohol use, or coexisting medical conditions. The results of this investigation suggest that signs and symptoms of depression are common neuropsychiatric disturbances in CA AD patients residing in the community.

Acamprosate for the treatment of alcohol dependence: a review of double-blind, placebo-controlled trials.

Acamprosate (calcium acetyl-homotaurine) is a synthetic compound that crosses the blood-brain barrier and has a chemical structure similar to that of the naturally occurring amino acid neuromediators, homotaurine and g-aminobutyric acid (GABA). Acamprosate appears to act primarily by restoring normal n-methyl-d-aspartate (NMDA) receptor tone in the glutamate system, and has been shown to have a specific dose-dependent effect on decreasing voluntary alcohol intake in animals with no effects on food and water consumption. The safety and efficacy of acamprosate in alcohol-dependent outpatients is currently under evaluation in the United States. Acamprosate has been available by prescription since 1989 in France and more recently in most European and Latin American coutries as well as Australia, South Africa, and Hong Kong. More than 4 million people have been treated with acamprosate since it became commercially available. The purpose of this article is to review all available double-blind, placebo-controlled clinical trials evaluating the safety and efficacy of acamprosate treatment of alcohol dependence. This work encompasses 16 controlled clinical trials conducted across 11 European countries and involves more than 4,500 outpatients with alcohol dependence. Fourteen of 16 studies found alcohol-dependent patients treated with acamprosate had a significantly greater rate of treatment completion, time to first drink, abstinence rate, and/or cumulative abstinence duration than patients treated with placebo. Additionally, a multinational open-label study of acamprosate in 1,281 patients with alcohol dependence found acamprosate to be equally effective across four major psychosocial concomitant treatment programs in maintaining abstinence and reducing consumption during any periods of relapse. An absence of known strong predictors of response to acamprosate, in conjunction with a modest but consistent effect on prolonging abstinence, and an excellent safety profile, lend support to the use of acamprosate across a broad range of patients with alcohol dependence.

Association between premorbid history of depression and current depression in Alzheimer's disease.

The relationship between a premorbid history of depression and the depressive syndrome in Alzheimer's disease (AD) remains equivocal. In the current study, we compared the prevalence of depression among patients with and without a history of mood disturbance prior to the onset of dementia. The sample comprised 243 AD outpatients evaluated consecutively at a university-affiliated memory disorders center. The results indicated that a positive history of depression was more common among patients with current depression compared to those without current depression (23% vs 11%, Fisher's Exact Test, P = .03). This relationship remained significant after controlling for the effects of age, education, gender, ethnicity, and level of cognitive impairment (odds ratio = 2.6, 95% confidence interval = 1.01-6.61, P = .04). Neither gender nor the interaction of gender and history of depression was shown to confer risk for current depressive symptoms. The present investigation suggests that premorbid depression may alter the risk for mood disturbance in AD.

Factors associated with depressive symptoms in non-demented community-dwelling elderly.

OBJECTIVE: We examined the risk for depressive symptoms associated with age, education, ethnicity, gender, marital status, apolipoprotein E genotype (APOE) and memory complaints among non-demented elderly (> or = 60 years). DESIGN: Cross-sectional study of geriatric patients recruited from a free memory screening offered to the community. SAMPLE: This investigation included 506 community-residing elderly subjects who were screened for cognitive impairment and classified as non-demented based on age and education-adjusted Folstein Mini-Mental State Exam (MMSAdj) scores of 24 or greater. RESULTS: The prevalence of significant depressive symptoms (Hamilton Depression Rating Scale > or = 12) was 12.1% (N = 61). Increased risk for depression was associated with female gender (OR = 2.3; 95% CI = 1.1-4.8; p < 0.05), Cuban American ethnicity (OR = 4.9; 95% CI = 2.3-10.4; p < 0.0001) and memory complaints (OR = 1.3; 95% CI = 1.2-1.4; p < 0.0001). The APOE allele frequencies in the current sample were 0.07, 0.80 and 0.13 for the epsilon 2, epsilon 3 and epsilon 4 alleles, respectively. CONCLUSIONS: The results suggest that signs and symptoms of depression are common among non-demented elderly subjects in the community. In this study, mood disturbances were associated with Cuban American ethnicity, female gender and more memory complaints. Factors that were not confirmed by this study include age, education, marital status and APOE genotype. The observed APOE, epsilon 4 allele frequency of 0.13 supports the normal cognitive classification of the sample.

Prevalence and correlates of Capgras syndrome in Alzheimer's disease.

OBJECTIVES: This study examined the prevalence and clinical correlates of Capgras syndrome (CS) in Alzheimer's disease. DESIGN: Cross-sectional study of elderly patients evaluated at an outpatient memory disorders clinic classified according to the presence or absence of CS. SUBJECTS: One hundred and fifty-one consecutive patients diagnosed with probable (N=110) or possible (N=48) Alzheimer's disease (AD) utilizing NINCDS-ADRDA diagnostic criteria. MATERIALS: The Behavioral Pathology in Alzheimer's Disease Rating Scale (BEHAVE-AD), Mini-Mental State Examination (MMSE) and Blessed Dementia Scale (BDS). RESULTS: CS was observed in 10% of the sample (N=16). Associated factors included other delusions, lower MMSE scores and higher BDS scores. The relation between CS and both cognitive and functional status remained significant after controlling for other delusions. CONCLUSION: CS was prevalent in approximately 10% of our community-dwelling AD sample. This syndrome was more common at the later stages of the illness and showed relations with increased functional impairment and other psychotic symptomatology.

Apolipoprotein-E (APO-E) genotype and symptoms of psychosis in Alzheimer's disease.

The authors examined the association of Apolipoprotein-E (APO-E) genotype to symptoms of psychosis and depression in 501 patients diagnosed with probable (n=343) or possible (n=158) Alzheimer's disease (AD) according to NINCDS-ADRDA criteria. They observed the following APO-E genotypes: epsilon2/epsilon3 (n=19); epsilon2/epsilon4 (n=14); epsilon3/epsilon3 (n=228); epsilon3/epsilon4 (n=203); epsilon4/epsilon4 (n=37). In contrast to previous reports, the results did not indicate a relationship between either the epsilon4 allele or the epsilon2 allele and symptoms of mood disturbance in AD. However, an elevated risk for psychosis was shown, specifically, at the severe stage of cognitive impairment, among AD patients carrying the epsilon4 allele, after effects of age, gender, education, and level of cognitive impairment were controlled.

A cross-ethnic analysis of risk factors for AD in white Hispanics and white non-Hispanics.

BACKGROUND: The prevalence of AD appears to vary widely in different ethnic groups. Certain risk factors for AD are well established for the general population, but there is little information regarding the relevance of these risk factors in specific ethnic groups. OBJECTIVE: The authors examined the risk of AD associated with the APOE-epsilon4 allele, the APOE-epsilon2 allele, smoking, alcohol consumption, history of hypertension, low educational level, estrogen replacement therapy, and history of head trauma with loss of consciousness among samples of white non-Hispanics (WNH) (392 AD patients, 202 normal subjects) and white Hispanics (WHIS) (188 AD patients, 84 normal controls). DESIGN: This was a case-control study of patients evaluated at an outpatient memory disorders clinic and control subjects recruited from a free memory screening offered to the community. RESULTS: Increased risk for AD was associated with the APOE-epsilon4 allele after controlling for age, education, and gender among WNH (OR = 3.5; 95% CI = 2.3 to 5.5) and WHIS (OR = 3.1; 95% CI = 1.7 to 5.8). No protective effect was conferred by the APOE-epsilon2 allele, although this relationship approached significance among WNH (p = 0.02). Low levels of education increased the risk for AD among WNH (OR = 3.1; 95% CI = 1.8 to 5.9) but not WHIS. Alcohol use and hypertension approached significance as risk factors in WNH (p < 0.05) but not WHIS. Estrogen replacement treatment approached significance as a protective factor in both ethnic groups (p < 0.05). CONCLUSIONS: Although the APOE-epsilon4 allele is a risk factor for AD among WHIS and WNH, other risk factors such as low education and hypertension appear to be important only for WNH. Risk factors for AD reported or suggested previously that were not confirmed by this study include smoking and head trauma with loss of consciousness.

Computational model of obsessive-compulsive disorder: examination of etiologic hypothesis and treatment strategies.

Research has shown that obsessive compulsive disorder (OCD) is related to structural and functional abnormalities in the brain, and several authors have organized these findings into theories of OCD neuropsychiatric dysfunction. In this paper, these theories were used to develop a neural network model of OCD. OCD symptoms were hypothesized to result from a hyperactive orbitofrontal-striato-thalamic-orbitofrontal neural loop. The network was constructed and trained with a backpropagation algorithm, and it was then used to assess etiologic theories of OCD (e.g., basal ganglia dysfunction, inadequate dopaminergic inhibitory influence on basal ganglia and excessive input from the limbic system). The network was also observed in analogues of the treatment of OCD with serotonergic medications and behavior therapy. Results show that a) the network behaved both normally and abnormally, depending on what combinations of perceptual, motivational, and neurochemical inputs were presented to it; b) several etiologic mechanisms produced changes in the networks' behaviors similar to patients' subjective experiences of OCD symptoms; and c) different treatment strategies, both those modeled as pharmacologic and behavioral therapies, produced reductions in simulated OCD symptoms.