Behavioral Disturbances In Dementia Research Articles

A Randomized, Double-Blind, Crossover Comparison of Risperidone and Haloperidol in Korean Dementia Patients With Behavioral Disturbances

Objective Behavioral disturbances in dementia are extremely prominent and distressful, and often result in serious physical, social, and economic consequences. The authors compared the efficacy and tolerability of risperidone and haloperidol in the treatment of behavioral and psychological symptoms of dementia (BPSD) in institutionalized elderly Korean patients with Alzheimer disease, vascular dementia, or mixed dementia. Methods This was an 18-week double-blind, crossover study involving 120 patients who were randomly assigned to receive flexible doses (0.5–1.5 mg/day) of risperidone or haloperidol. BPSD were assessed using the Korean version of the Behavioral Pathology in Alzheimer's Disease Rating Scale (BEHAVE-AD-K), the Korean version of the Cohen-Mansfield Agitation Inventory (CMAI-K), and the Clinical Global Impression of Change scale (CGI-C). Safety and tolerability assessments included the Extrapyramidal Symptom Rating Scale and the incidence of adverse events. Results Both risperidone and haloperidol were efficacious in alleviating BPSD. However, when receiving risperidone, patients showed significantly greater improvement than when receiving haloperidol in the total and subscale scores of the BEHAVE-AD-K, the total and subscale scores of the CMAI-K, and the scores on the CGI-C scale. Also, risperidone had an additional benefit on aggressiveness and anxieties/phobias. The risk of antipsychotic-induced parkinsonism throughout this study was significantly lower with risperidone than with haloperidol. Conclusion Risperidone had a favorable efficacy and tolerability profile compared with haloperidol in the treatment of BPSD in this patient population.

Citalopram, a selective serotonin reuptake inhibitor augments harmaline-induced tremor in rats

Citalopram, a serotonin reuptake inhibitor (SSRI) is one of the widely used antidepressants. Apart from its antidepressant activity citalopram is also used for anxiety, panic disorders, obsessive-compulsive disorder and behavioral disturbances of dementia. Tremor is the second most common neurological adverse effect in patients receiving treatment with SSRIs. Use of these agents in depressed patients with essential tremor has not been studied. The present study was undertaken to investigate the effect of chronic citalopram treatment on harmaline-induced tremors in rats. Female Sprague–Dawley rats weighing 70±2 g were given citalopram in doses of 0, 10, 20 and 40 mg/kg by gavage for 2 weeks. On the 15th day, the rats were given harmaline (10 mg/kg, i.p.) 30 min after the last dose of citalopram. The latency of onset, intensity and duration of tremor and EMG were recorded. Serotonin (5HT) and 5-hydroxy indole acetic acid (5HIAA) were measured in brain stem. Citalopram dose dependently exacerbated the duration, intensity and amplitude of EMG of harmaline-induced tremor. A significant decrease in 5HT turnover (5HIAA/5HT ratio) in the brain stem was observed suggesting a possible role of serotoninergic impairment in citalopram-induced augmentation of harmaline-induced tremor. Clinical implications of these observations warrant further investigation.

Treatment of the Neuropsychiatric Symptoms in Alzheimer's Disease

Behavioral symptoms are common in Alzheimer’s disease (AD) and represent a major source of the disease morbidity. Neuropsychiatric disturbances have been associated with more rapid cognitive decline (1), increased caregiver burden (2,3), increases in patient care costs due to earlier institutionalization of the AD patient, greater medication use and more adverse side effects and more extensive institutional staffing needs (4,5). Kaufer and colleagues (6) reported a strong correlation between the amount of neuropsychiatric disturbance as measured by the Neuropsychiatric Inventory (NPI) and the degree of caregiver distress with little relationship between the degree of impairment on the Mini-Mental State Exam (MMSE) (7) and the degree of caregiver distress. In addition, a recent cost analysis showed that AD patients with higher NPI scores (worse psychopathology) had formal costs between $3,162 and $5,919 higher than those with low NPI scores and the total direct costs between $10, 670, and $16,141 higher, depending on the severity of cognitive impairments (8). Clinical research on the treatment of these non-cognitive symptoms has only recently become a subject of major investigation. Clinical drug trials of new therapeutic agents in AD are beginning to regularly include specific scales to measure potential changes in behavioral symptoms with respect to their therapeutic interventions. In addition, an increasing number of randomized, placebo-controlled clinical trials of a wide variety of psychotropic medications to treat significant behavioral disturbances in dementia are beginning to emerge. The successful management of troublesome behaviors associated with AD can significantly improve the overall quality of life for patients and their caregivers and could result in significant relevant benefit.

Treatment of the neuropsychiatric symptoms in Alzheimer's disease.

Behavioral symptoms are common in Alzheimer’s disease (AD) and represent a major source of the disease morbidity. Neuropsychiatric disturbances have been associated with more rapid cognitive decline (1), increased caregiver burden (2,3), increases in patient care costs due to earlier institutionalization of the AD patient, greater medication use and more adverse side effects and more extensive institutional staffing needs (4,5). Kaufer and colleagues (6) reported a strong correlation between the amount of neuropsychiatric disturbance as measured by the Neuropsychiatric Inventory (NPI) and the degree of caregiver distress with little relationship between the degree of impairment on the Mini-Mental State Exam (MMSE) (7) and the degree of caregiver distress. In addition, a recent cost analysis showed that AD patients with higher NPI scores (worse psychopathology) had formal costs between $3,162 and $5,919 higher than those with low NPI scores and the total direct costs between $10, 670, and $16,141 higher, depending on the severity of cognitive impairments (8). Clinical research on the treatment of these non-cognitive symptoms has only recently become a subject of major investigation. Clinical drug trials of new therapeutic agents in AD are beginning to regularly include specific scales to measure potential changes in behavioral symptoms with respect to their therapeutic interventions. In addition, an increasing number of randomized, placebo-controlled clinical trials of a wide variety of psychotropic medications to treat significant behavioral disturbances in dementia are beginning to emerge. The successful management of troublesome behaviors associated with AD can significantly improve the overall quality of life for patients and their caregivers and could result in significant relevant benefit.

The Incidence of Mental and Behavioral Disturbances in Dementia: The Cache County Study

A population-based prevalence sample of 355 residents of Cache County, Utah, who were diagnosed with dementia, was rated on the Neuropsychiatric Inventory (NPI). Of the 355 residents, 119 had no neuropsychiatric symptoms at baseline and were, consequently, at risk for incident mental and behavioral disturbances. The NPI was readministered approximately 18 months later to 61 surviving participants. Sixty-nine percent developed at least one mental or behavioral symptom. Delusions were most common (28%), followed by apathy (21%), and aberrant motor behavior (21%). When this incidence rate of 69% was combined with a previously estimated prevalence rate of 61%, the cumulative 18-month prevalence approached 90%. These results argue for a routine assessment of psychiatric disturbances in all patients with dementia, even among those who have never experienced symptoms of mental or behavioral disturbances.

Quality Care: A Practical Guide to Managing Behavioral Symptoms of Dementia

Although cognitive impairments usually precede the development of behavioral disturbances in dementia, it is the latter that most often precipitate caregiver burnout and requests for medical intervention and/or institutionalization.

Recognition and Management of Behavioral Disturbances in Dementia.

Behavioral disturbances are seen in most patients with dementia at some point in their course. They cause immense patient suffering and are responsible for caregiver stress, institutionalization, and hospitalization. Identification of predisposing and precipitating factors is very important. The approach to the management of behavioral disturbances in dementia patients should be structured and thorough. Ensuring the safety of the patient and others should be paramount. Addressing the causes of behavioral disturbances such as comorbid medical illnesses, polypharmacy, pain, personal need, environmental factors, etc. is critical to a successful outcome. Many behavioral disturbances such as wandering and hoarding are not amenable to pharmacotherapy. Nonpharmacologic interventions are the mainstay of managing behavioral disturbances. Success of pharmacologic interventions will depend on accurate identification of specific syndromes, e.g., depression-anxiety and psychosis and severity of symptoms. Response to pharmacologic interventions is usually modest and may be associated with significant symptom resolution. Many behavioral disturbances can be prevented by avoiding inappropriate medications and educating patient, family, caregivers, and health care providers. Hospitalization can be avoided and institutionalization delayed by early recognition and treatment of behavioral disturbances. Leadership from physicians to implement preventive measures is recommended. Research to clarify the biological underpinnings of behavioral disturbances and to address cost-effectiveness of currently identified interventions is needed.

Cholinesterase inhibitors for behavioral disturbance in dementia.

The authors review the literature from the last year examining the benefits of cholinesterase inhibitors in the treatment of behavioral disturbance in Alzheimer's disease (AD) and other dementias. Previous review has indicated that cholinesterase inhibitors have psychotropic properties. We found more evidence to support both the benefits of cholinesterase inhibitors in behavioral disturbance, and that specific behaviors may be selectively responsive to treatment.

Contribution of PTSD/POW history to behavioral disturbances in dementia.

As many World War II and Korean Conflict veterans suffering from posttraumatic stress disorder (PTSD) grow older, increasing numbers will be diagnosed with dementia. We retrospectively analyzed patients with dementia, comparing the behavioral disturbances of those with PTSD to those without PTSD. We hypothesized that due to the additive effect of the neurobiological and behavioral changes associated with PTSD and dementia, the dementia with PTSD group would show more agitation and disinhibition than the dementia without PTSD group. Sixteen patients with diagnoses of dementia and PTSD were matched on age and Mini-Mental States Examination (MMSE) scores to 16 patients with dementia without PTSD. Demographic characteristics, co-morbid diagnoses, global Assessment of Functioning (GAF), Cohen-Mansfield Agitation Inventory (CMAI), and paranoid items of Brief Psychiatric Rating Scale (BPRS) and Positive and Negative Syndrome Scale for Schizophrenia (PANSS) were assessed. The patients with diagnoses of dementia with PTSD did not differ significantly in their clinical presentation, hospital course, and condition at discharge from patients with dementia without PTSD. Chi-square analysis showed that significantly more subjects in the PTSD group were prescribed anti-depressants compared to the non-PTSD group. Interestingly, within the PTSD group, the subgroup of patients who were former prisoners of war had a significantly higher mean score for paranoia and significantly less verbal agitation. This pilot study reveals that a diagnosis of PTSD alone is not sufficient to influence behavior in veterans with dementia; however, we also present provocative results that patients with more severe trauma (POW) do have changes in their behavior.

Indications for the Use of Atypical Antipsychotics in the Elderly

There has been an expanding role for the new generation atypical antipsychotic agents (clozapine, risperidone, olanzapine, and quetiapine) in elderly patients. Their efficacy in the treatment of psychoses associated with schizophrenia is now well established. But psychoses occur in other conditions. This paper will review the current research examining the use of the atypical agents in the treatment of psychoses in the elderly in three somewhat overlapping conditions: schizophrenia, dementia, and Parkinson's disease, as well as in the amelioration of a variety of movement disorders. In the elderly, any of the atypicals can be used to treat schizophrenia, although clozapine may be a second line agent because of its side effect profile. Risperidone may be the drug of choice for the treatment of psychoses and behavioral disturbances in dementia. Clozapine is a primary choice and quetiapine an alternative for the treatment of psychoses in Parkinson's disease; while clozapine and possibly risperidone may be preferred for the initial treatment of some movement disorders. The differential effectiveness of these agents across treatment indications may, in part, be related to their differing affinities at several neurotransmitter receptors. Examination of these relationships in large scale longitudinal studies may help in the development of effective tailored treatments for the elderly.

The use of typical and atypical neuroleptics for controlling behavioral disturbances in dementia: A retrospective study

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) is well known as an exogenous dopaminergic neurotoxin that induces Parkinson's disease-like symptoms. In addition, 1,2,3,4-tetrahydroisoquinoline (TIQ) derivatives have been investigated as endogenous MPTP mimetic compounds that structurally resemble selegiline, a commercially available drug for treating Parkinson's disease. In the present study, we examined the ability of 1,3-dimethyl-TIQ (1,3-diMeTIQ) and 1,3-dimethyl-N-propargyl-TIQ (1,3-diMe-N-proTIQ) to prevent MPTP-induced Parkinson's disease-like symptoms in mice and to prevent 1-methyl-4-phenylpyridinium ion (MPP+, an active metabolite of MPTP)-induced cytotoxicity in vitro, including its structural stereoselectivity. Repeated administration of MPTP induced bradykinesia, a symptom of behavioral abnormality; this was prevented by both 1,3-diMeTIQ and 1,3-diMe-N-proTIQ pretreatments. Pretreatment with 1,3-diMeTIQ did not prevent the MPTP-induced decrease in dopamine content in the striatum or the decrease in the number of tyrosine hydroxylase-positive cells in the substantia nigra. On the other hand, 1,3-diMe-N-proTIQ prevented these Parkinson's disease-like symptoms; in particular, the trans-isomer of this agent showed potent protective effects. However, the ability of the trans-1,3-diMe-N-proTIQ isomer to prevent MPP+-induced PC12 cell death was weaker than that of its cis-isomer. Thus, stereoisomers of 1,3-diMe-N-proTIQ exhibit different effects; cis-1,3-diMe-N-proTIQ inhibits MPP+-induced cytotoxicity while trans-1,3-diMe-N-proTIQ exhibits neuroprotective effects primarily through MPTP-related biological events in mice. These results also indicate the possibility of utilizing, at least in part, the stereoselective efficacy of 1,3-diMe-N-proTIQ against MPTP and/or MPP+-induced adverse states.

Introduction

This special issue of International Psychogeriatrics, “Behavioral and Psychological Symptoms of Dementia: A Clinical and Research Update,” contains the proceedings of a conference held in Lansdowne, Virginia, May 11–13, 1999. It is a sequel to a previous issue that was based on the first international Consensus Conference on Behavioral Disturbances of Dementia (Lansdowne, Virginia, March 31–April 2, 1996). The rationale for the second conference was the growing interest in the symptoms of dementia (e.g., physical aggression, delusions, wandering) that result in premature institutionalization, emotional suffering for patients and caregivers, increased financial costs, and excess disability.

A Comparison of Symptoms of Behavioral Disturbances in Yoruba and African American Individuals With Dementia

Comparative cross-cultural studies represent a great opportunity for delineating risk factors for the dementias by providing a much wider diversity of both environmental exposures and genetic variation than studies within industrialized countries. Similarly, studies of the behavioral disturbances of dementia that allow for identification of similarities and differences may be useful both in understanding the etiology of these disorders and in determining the best approach to management. So far, few such comparative studies exist.

Mental and behavioral disturbances in dementia: Findings from the cache county study on memory in aging

Mental and behavioral disturbances in dementia: Findings from the cache county study on memory in aging

The assessment of behavioral disturbances in dementia using a telemetric device

The assessment of behavioral disturbances in dementia using a telemetric device

Mental and behavioral disturbances in dementia: findings from the Cache County Study on Memory in Aging.

The authors report findings from a study of 5,092 community residents who constituted 90% of the elderly resident population of Cache County, Utah. 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. 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. 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.

Bright light therapy for demented nursing home patients with behavioral disturbance

The objective of this study was to examine the effects of morning bright light on behavioral disturbances in dementia using a repeated measures ABA design. We hypothesized that morning bright light in demented patients reduces the agitation rating and directly observed disruptive behavior, but increases observed positive behavior. The study was done in a special care unit of a long term care facility, with 16 demented residents ages 60 to 89, 13 female and three male. Morning bright light (Day-Light Box 10000, produced by DayLight Technologies, Inc, providing 10,000 lux) was administered Monday to Friday during the treatment week. The Global Deterioration Scale rating at baseline, followed by baseline, treatment and post-treatment ratings in the Cohen-Mansfield Agitation Inventory (CMAI) and Environment-Behavior Interaction Code (EBIC) were used as measurements Compared to baseline, the mean total Cohen-Mansfield score decreased more during the phototherapy week than during the post-treatment week (p < 0.05 on one-tailed paired t-test). Regardless of phototherapy, Cohen-Mansfield scores decreased significantly in summer versus fall-spring (p < .005). Although the direct behavioral measures [EBIC] showed no statistically significant change compared to baseline, there was a pattern of greater mean increase in positive behaviors (p = .08) during phototherapy than in the post-treatment week, and a mean decrease of total disruptive behaviors most pronounced in the post-treatment week (p = .05). Bright light therapy has modest efficacy in reducing agitation, with possible concurrent improvement in positive behaviors. Disruptive behaviors may also become less frequent during phototherapy with evidence of even greater delayed optimal effect. Further research should focus on subgroups of patients demonstrating a particularly robust response, enhance power through a larger sample, provide for longer light exposure, and control for seasonal variables.

Contribution of psychosis and depression to behavioral disturbances in geropsychiatric inpatients with dementia.

Specific behavioral disturbances in dementia may be associated with underlying disorders such as the presence of psychosis and depression. The objective of this study was to examine the association of depression and psychosis with behavioral disturbances in geropsychiatric inpatients with dementia. All admissions between October 1993 and May 1995 were reviewed to identify those patients admitted to the Houston Veterans Affairs Geropsychiatry Unit with a diagnosis of dementia; 208 patients were included in the study. Hierarchical regression models were constructed to explore the contribution of depressive and psychotic symptoms, and depression and psychosis diagnoses to Cohen-Mansfield Agitation Inventory (CMAI) scores. Both depression and psychotic symptoms were significantly and positively correlated with behavioral disturbances. Psychotic symptoms were associated with aggressive behavioral symptoms, and depressive symptoms were associated with constant requests for help, complaining, and negativism. Dementia severity accounted for significant variance in CMAI scores and was positively associated with behavioral disturbance; though disorder symptoms accounted for more behavioral disturbance variance than did depressive symptoms. Both depressive and psychotic symptoms were associated with overall behavioral disturbances in patients with dementia. Psychotic symptoms and depressive symptoms were associated with different types of behavioral disturbances. Our findings support the contention that underlying depression or psychosis may partially account for different behavioral disturbances and that not all behavioral disturbances should be globally labeled "agitation." Future studies should address symptom-specific treatment of behaviorally disturbed patients.

Guidelines for the Appropriate Use of Cholinesterase Inhibitors in Patients with Alzheimer??s Disease

The cholinesterase inhibitors are the only available scientifically proven symptomatic treatments for dementia of the Alzheimer’s type. The guidelines we present summarise the current updated knowledge on the available drugs, including tacrine, donepezil, rivastigmine, metrifonate and galantamine (galanthamine). Each of these drugs have been proven to be more effective than placebo in improving symptoms in well designed, double-blind, placebo-controlled studies. Although tacrine was the first drug approved by the US Food and Drug Administration, it needs frequent monitoring of alanine amino transferase levels. Hence, donepezil emerged as a frequently prescribed drug for dementia of the Alzheimer’s type, secondary to its ease of use and lack of significant adverse effects. More studies are needed regarding long term efficacy, head-to-head comparisons and effects upon behavioural disturbances in dementia of the Alzheimer’s type. These guidelines will provide the starting point for a wider clinical use because, although available and clinically effective, the cholinesterase inhibitors are under-prescribed by clinicians in the pharmacological treatment of Alzheimer’s disease.

Psychosis and behavioral disturbances in dementia: Effects of risperidone in 969 patients

To determine the extent to which frontal executive impairment early in the course of dementia is predictive of subsequent disturbed behavior.This was a prospective follow-up study set in the Memory Clinic, Leicester, United Kingdom. A patient cohort (N = 42) diagnosed with mild to moderate dementia was followed up between three and six years after initial assessment. Executive function at baseline was assessed using the The Cambridge Examination for Mental Disorders of the Elderly–Revised (CAMCOG-R) Executive Function score. Disturbed behavior and caregiver distress at follow-up were assessed on the Neuropsychiatric Inventory (NPI), Cohen-Mansfield Agitation Inventory (CMAI), and Dementia Apathy Interview and Rating (DAIR).After adjustment, the Executive Function score at baseline was predictive of disturbed behavior and caregiver distress (NPI, CMAI, DAIR) at follow up, with higher levels of executive impairment associated with higher levels of disturbance/distress. Baseline measures of global cognitive impairment (Mini-Mental State Exam, CAMCOG) were not predictive of subsequent disturbed behavior or caregiver distress.Executive impairments identifiable relatively early in the clinical course of dementia are predictive of disturbed behavior and associated caregiver distress at long-term follow-up, which supports the view that executive dysfunction is important in the etiology of these problems.