Troublesome and disruptive behaviors in dementia. Relationships to diagnosis and disease severity

Patients with dementia often manifest troublesome and disruptive behaviors in addition to intellectual impairments. This study evaluated behavioral disturbances in 126 demented patients examined sequentially, using questionnaires administered to primary caregivers to quantify the types and severity of behavioral disturbances. Eighty-three percent of the patients exhibited one or more of the targeted behaviors. The most common troublesome and disruptive behaviors clustered into three categories: aggressive, ideational, and vegetative. The prevalence and severity of the behaviors increased with global severity of dementia, but did not differ in either frequency or type when patients with three diagnoses were compared: Alzheimer's disease (AD), multi-infarct dementia (MID), and mixed AD and MID (MIX). The occurrence and severity of the target behaviors correlated modestly with the severity of dementia. Impairments of mental status correlated weakly with only a single troublesome and disruptive behavior--assaultiveness. These results suggest that troublesome and disruptive behaviors are a very frequent component of dementing disorders, are related to disease severity, and parallel (but are probably not determined by) intellectual deficit.     

Anxiety of Alzheimer's disease: prevalence, and comorbidity.

BACKGROUND: Anxiety may be associated with psychiatric morbidity, disability, increased health care utilization, and mortality in Alzheimer's disease (AD) patients as it is in the general adult population. However, the phenomenology of anxiety symptoms in AD and its relationship to dementia progression, comorbid depression, and the presence of other problematic behaviors have not yet been examined. METHOD: Data on anxiety symptoms and their coexistence with other factors were obtained in 523 community-dwelling AD patients through interviews with their caregivers and direct physical examination. The prevalence of anxiety symptoms and their association to patient depression, other behavioral problems, gender, and age was investigated. RESULTS: Anxiety symptoms were common, occurring in 70% of subjects. Anxiety symptoms were significantly correlated with ADL impairment and other behavioral disturbances, including wandering, sexual misconduct, hallucinations, verbal threats, and physical abuse. Comorbidity of anxiety-depression was also prevalent: 54% of the sample had both anxiety and depression symptoms. ADL impairment and problem behaviors were significantly associated with comorbidity; however, the latter association was explained entirely by the presence of anxiety. CONCLUSION: Anxiety symptoms were common and significantly related to ADL and additional neuropsychiatric problems in this sample. These results indicate the need for additional research into the phenomenology of anxiety and comorbid anxiety-depression in AD and for the development and investigation of effective assessment and treatment of anxiety in AD clinical practice.     

Assessment of behavioral and psychological symptoms of dementia by family caregivers

This study was designed to test the performance and related factors of a self-administered instrument in assessing behavioral and psychological symptoms of dementia (BPSD) by family caregivers. We recruited 173 patients with dementia and major caregivers from two neurological clinics. Information about clinical diagnosis, the Mini Mental State Examination (MMSE), the Clinical Dementia Rating (CDR), the Dementia Behavior Disturbance Inventory (DBDI), and global caregivers’ strain were collected from interview and chart review. We found that DBDI has acceptable construct validity and good internal consistency reliability. BPSD was more frequently found in patients with advanced dementia, poor cognitive function and highly correlated to caregivers’ strain. Multivariate analysis revealed that female patients and caregivers, advanced CDR stages, patient-caregiver relationship, types of dementia and MMSE score were related to the increase of frequency and disturbance index of DBDI. We concluded that BPSD could be evaluated by family caregivers using a self-administered instrument. Further study is indicated to clarify how caregiver characteristics affect the report of behavioral symptoms, and its clinical importance.     

Dementia without cholinergic deficit

We examined the role of cholinergic system in multi-infarct dementia (MID) by measuring acetylcholinesterase (AChE) activities in cerebrospinal fluid (CSF) of clinically diagnosed MID patients, Alzheimer's disease (AD) patients and controls. In spite of the similar clinical severity of dementia, MID patients had unaltered AChE levels, whereas AD patients had significantly reduced AChE levels in CSF when compared to controls. In the autopsy study we analyzed choline acetyltransferase (ChAT) levels in four cortical brain areas from clinically and neuropathologically studied AD patients, demented non-AD patients and controls. ChAT activities in the cerebral cortex in non-AD patients were on the same level as in controls, but AD patients had a marked loss of ChAT activity in all four cortical brain areas studied. Although cholinergic deficit is a usual phenomenon associated with cognitive failure, severe dementia can exist without cholinergic dysfunction.     

Longitudinal course of behavioral problems during Alzheimer's disease: linear versus curvilinear patterns of decline

BACKGROUND: Patients with Alzheimer's Disease (AD) are commonly assumed to experience a linear decline in behavioral functioning that parallels progressive cognitive decline. However, some researchers have suggested that specific behavioral problems either decline at different rates or improve in late dementia. METHODS: The present analyses examined 150 AD patients at an initial assessment, 61 of whom were also evaluated annually on two additional occasions. Measures of cognitive impairment and behavioral problems were obtained. RESULTS: Cross-sectional results indicated curvilinear associations between dementia severity and certain behavioral problems (forgetful behaviors, and emotional and impulsive behaviors). Longitudinal analyses further indicated trends for curvilinear rates of behavioral disturbance across time, with some problem areas showing improvement as AD progresses through the most severe stages. CONCLUSIONS: Even though Alzheimer's disease is a progressive dementia characterized by increasing cognitive deterioration, it appears to be inaccurate to expect behavioral functioning to show the same linear decline across time.     

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

BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.     

Determinants of burden in an Italian sample of Alzheimer's patient caregivers

The association between caregiver's stress and depressive symptoms, and sociodemographic and clinical characteristics of Alzheimer's patients and caregivers was evaluated in 63 primary caregivers consecutively recruited at the Alzheimer's Dementia Research and Care Unit of Brescia, northern Italy. Family caregivers' informal support was also evaluated. Patients' behavioral disturbances, and the number of persons who lived in the household were the main correlates of caregivers' stress. The greater the number of persons, the lower the report of caregiver stress. Lower frequency of visits of friends or relatives, caregivers' poor health and higher age, and the presence of patients' behavioral disturbances were the main determinants of caregivers' depressive symptoms. Cognitive impairment of patients was not correlated to caregivers' distress. Our study underlines that the imperatives of dementia and caregiving appear to be so significant that they have similar consequences in the Italian population as well as in other very different cultures. Factors related to primary caregivers, other than patients' behavior, such as informal supports or caregivers' health and age, should be taken into account in the evaluation of caregivers' burden.     

Neuropsychiatric assessment of Alzheimer's disease and related dementias.

Alzheimer's disease (AD) patients exhibit a variety of behavioral alterations including agitation, apathy, depression, anxiety, delusions, irritability and disinhibition. Most patients with AD exhibit neuropsychiatric symptoms, and behavioral changes become more frequent with advancing disease severity. The NPI is a valid and reliable means of assessing neuropsychiatric symptoms in patients with dementia. The NPI correlates with increasing disability in activities of daily living and increasing cognitive impairment. Physical illness contributes little to behavioral symptoms measured by the NPI. Reduced frontal lobe metabolism and perfusion have been identified in patients with apathy, agitation, psychosis and depression. Patients with elevated agitation scores on the NPI have a higher burden of frontal lobe neurofibrillary tangles than patients without agitation. The NPI is sensitive to behavioral improvements following treatment with cholinesterase inhibitors and psychotropic agents. Neuropsychiatric symptom profiles differ among dementia syndromes, and the NPI provides a means of assessing neuropsychiatric symptoms that may aid in differential diagnosis. Evaluation of neuropsychiatric symptoms is a critical aspect of dementia diagnosis and management.     

Dementia of the Alzheimer type and multi-infarct dementia: a clinical description and diagnostic problems

Patients who had Alzheimer's disease-senile dementia of the Alzheimer type (AD/SDAT) or multi-infarct dementia (MID) were compared with a group of controls. Demented patients had approximately the same degree of dementia and the same duration of illness. The MID group had a significantly higher mean age than the AD/SDAT group. Sixty-three per cent of the AD/SDAT patients were free of other diseases, while 65 per cent of the MID patients had cardiovascular disease. Thirty per cent of the MID patients had a history of previous depression, while only 5 per cent of the AD/SDAT patients had had depression. At the time of the investigation, however, AD/SDAT patients showed significantly more signs of depression than the MID patients. Focal neurologic signs were found in 70 per cent of the MID patients and only 6 per cent of the AD/SDAT patients. The electrocardiogram was normal for every AD/SDAT patient, while 75 per cent of the MID patients had abnormal ECGs. Electroencephalography showed generalized slow frequencies in 79 per cent of the AD/SDAT patients and localized slow frequencies and abnormalities in 65 per cent of the MID patients. Computed tomography of the brain showed that MID patients had significantly greater dilation of the ventricular system, while cortical atrophy did not differ significantly among the three groups. Homovanillic acid in the cerebrospinal fluid was significantly lower in the AD/SDAT group as compared with controls.     

Behavioral and psychological symptoms, cognitive impairment and caregiver burden related to Alzheimer's disease patients treated in an outpatient memory clinic

AIM: The relationships among behavioral and psychological symptoms of dementia (BPSD), cognitive impairment of Alzheimer's disease (AD) patients and the caregiver burden of their caregivers were investigated in an outpatient memory clinic. METHODS: Forty-six pairs of AD patients and their family caregivers were involved in this study. Neuropsychiatry Inventory (NPI) was used to estimate BPSD, to which memory symptoms were added as a subcategory of BPSD. MMSE, word fluency, clock drawing test and category-cued memory test were used for cognitive measurement. Zarit burden interview (ZBI) and CES-D were used to assess caregiver burden. RESULTS: Among 11 BPSD subcategories, memory symptoms, apathy, depression, delusion, aggression and anxiety were prevalent BPSD was a strong determinant of caregiver burden. Among BPSD symptoms, anxiety, aggression and aberrant motor behavior were significantly related to ZBL In terms of the relationship between BPSD and cognitive impairment, the scores for delusion and apathy were significantly related to the cognitive decline. On the other hand, patients who showed symptoms related to memory and depression had higher cognitive function than those who did not. CONCLUSION: These analyses will contribute to better assessment of AD patients and their caregivers, hopefully resulting in better support for them.     

Medical Management of Advanced Dementia

A cure for Alzheimer's disease (AD) is still far off, and clinicians face the burden of caring for patients at all stages of dementia for the foreseeable future. Those with advanced disease suffer neurological symptoms and signs that include incontinence; problems with gait and mobility; marked cognitive, language, and functional impairment; and in about 90% of patients, significant behavior problems. Dementia precludes the ability to initiate meaningful activities or social interactions. Whether patients are resident in the community or living in a nursing home, this composite reflects a highly complex medical and neuropsychiatric management challenge. Predictable medical conditions also must be addressed (i.e., those that accompany dementia, such as parkinsonism, and those that are prevalent in any aging population, such as hypertension).
Clinicians can better address these problems with awareness of current treatment options. Placebo-controlled trials of some psychotropic agents have shown modest favorable effects on behavior problems. Use of acetylcholinesterase inhibitors (AChEIs) to treat cognitive impairment and secondary behavioral symptoms derives primarily from results of placebo-controlled clinical trials. Trials in patients with moderate to severe AD, outpatients as well as nursing home residents, show overall effects similar to those seen in outpatients with milder dementia. Treatment with AChEIs may delay institutional placement. Memantine has shown benefit in trials in moderate to severe dementia, although it is not yet approved in the United States. Emerging data have expanded physicians' ability to use pharmacotherapy in patients with advanced dementia. Physicians need to enact the principle that something can be done for our afflicted parents and grandparents.     

The validity of informant report for grading the severity of Alzheimer's dementia

The validity of informant-based techniques has been established for the detection of dementia cases by non-pathological individuals, but is still controversial for the assessment of the severity of dementia. This study aimed at ascertaining whether informant-based evaluation (the so-called informant report) of the cognitive and behavioral impairment of a patient is valid for grading the severity of dementia, and consistent with objective assessment of the patient's cognitive and behavioral functioning. We enrolled 96 community-dwelling outpatients and 56 controls assessed at the Geriatric Evaluation Unit of the University of Modena, Italy. All patients scored lower than 27 on the MMSE, and met DSM-IV inclusion criteria for Alzheimer's dementia. Patients and controls were administered the CAMDEX interview, containing a section which collects participant (patient or control) and informant evaluations on dementia-related cognitive and behavioral deficits. The informant report resulted effective at MANOVA for grading the severity of dementia in 4 of its 5 measures (namely, memory, everyday activities, general mental functioning and depressed mood), and was correlated with the scores of several scales of the CAMDEX cognitive section (i.e., CAMCOG). Instead, the participant's (patient or control) report showed a lower capacity for grading dementia, and was poorly correlated with the psychometric outcomes of cognitive functioning. On the whole, the results corroborated the validity of the informant report in the diagnostic work-up for grading dementia, given its sensitivity to the severity of dementia, and its consistency with cognitive psychometric outcomes.     

A prospective study of dementia with Lewy bodies

BACKGROUND: little is known about the longitudinal course of dementia with Lewy bodies (DLB) and how this differs from Alzheimer's disease (AD). METHOD: standardized baseline and annual assessments of cognitive and non-cognitive symptoms are reported in a cohort of 72 patients with DLB or AD. AD was diagnosed using the NINCDS ADRDA criteria and DLB was diagnosed with the criteria of McKeith et al. Cognitive assessment was undertaken using the MMSE schedule and operationalized definitions were used to diagnose non-cognitive symptoms. RESULTS: 42 patients with DLB and 30 patients with AD were assessed. Of the 19 on whom post mortem examinations have been performed, 18 (95%) have had the clinical diagnosis confirmed. DLB patients were significantly more likely to experience visual hallucinations, disturbances of consciousness and parkinsonism at both baseline and at annual assessments. Of DLB patients exposed to neuroleptics, 33% developed sensitivity reactions. The magnitude and pattern of cognitive decline was similar in both groups. CONCLUSION: the importance of the core features highlighted in the newly proposed consensus DLB criteria is supported. These features appear to be stable over time.     

Copy task performance and urinary incontinence in Alzheimer's disease

The relationship between behavioral symptoms and cognitive impairment in Alzheimer's Disease (AD) is only poorly understood. The aim of the present study was to examine cognitive correlates of urinary incontinence in AD. Although incontinence is generally accepted as an accompaniment of AD, it was our clinical impression that it correlated poorly with global measures of cognitive impairment. A retrospective pilot study of 17 incontinent demented patients and 17 continent patients, matched for age, sex, and total score on the Folstein Mini-Mental Status Exam (MMSE), revealed a striking association between an inability to do a copy task and urinary incontinence. A prospective study confirmed this finding in a sample of 45 patients meeting DSMIII-R diagnostic criteria for dementia, probable Alzheimer's disease. The 17 incontinent patients did not differ from the 28 continent patients in age, sex distribution, or total score on the MMSE. However, the incontinent subjects scored significantly lower on a cube copying task. Qualitative analysis revealed that the drawings by incontinent patients showed features comparable with those observed in the drawings by patients with right-sided parietal lesions, in particular, poor representation of perspective and spatial orientation. Further investigation of the relationship between copying performance and incontinence may have implications for understanding the cortical mechanisms of urinary continence. The present results also underscore the limitations of the MMSE as a measure of dementia severity and suggest there are areas of cognitive ability which are inadequately assessed by MMSE but which may be of major important in understanding the loss of functional skills in the dementing patient.     

Pharmacological treatment of Alzheimer's Disease

BACKGROUND AND AIMS: The treatment of Alzheimer's disease (AD) is a challenge for physician, families, and patients. An individualized, multimodal treatment plan addressing the treatment of cognitive, behavioural and functional decline is essential. Aim of the paper is to describe the principal components of the treatment plan of AD patients. METHODS: A review of the recent literature was performed. RESULTS: Acetylcholinesterase inhibitors (AChEIs) play an important role in the improvement of cognitive decline in mild to moderate AD, even if the improvement is not permanent. Data obtained from the CRONOS project (involving about 500 Alzheimer Evaluation Units) replicate in the real world those obtained in controlled trials, confirming that AD patients may benefit from AChEI treatment. Treatment of behavioral and psychological symptoms of dementia (BPSD) requires education of caregivers, non pharmacological interventions, identification and treatment of medical illnesses or environmental precipitating conditions, specific pharmacological treatment. Traditional neuroleptics are widely used for BPSD treatment, but limited data support their use, and side-effects are frequent and severe. Atypical antipsychotics are effective in treating BPSD, and safer than traditional neuroleptics. However, the increased risk of cerebrovascular accident in patients taking risperidone or olanzapine limited currently their use in demented subjects. The use of antidepressant drugs, as well as behavioral approach, may improve depressive symptoms frequently accompanying AD. CONCLUSIONS: Although at present there is no cure for AD, several drug treatments and care strategies may improve or stabilize cognitive and behavioral symptoms, and improve the quality of life of patients and families.     

Dementia: case ascertainment in a community survey

The three-stage East Baltimore Mental Health Survey, conducted in 1981 as part of the Epidemiological Catchment Area Program, provided an opportunity to assess the prevalence of dementia and specific dementing disorders in a community-based, cross-sectional sample of the population. From the 3,841 households originally sampled, 810 individuals were selected for clinical psychiatric evaluation. Forty-one individuals were given a provisional diagnosis and referred to Stage 3 for differential diagnosis, with 32 individuals completing this evaluation. Thorough clinical evaluation of these cases resulted in an overall prevalence of dementia of 4.5% in those 65 years of age and older. The prevalence of specific dementing disorders was Alzheimer's disease (AD) (2.0%), Multi-Infarct Dementia (MID) (2.0%) and Mixed Dementia (MD) (0.5%). Prevalence increased with age for all dementias: Non-Whites had higher rates of dementia than Whites; females had higher rates of AD while males had higher rates of MID; and the prevalence of AD increased with increasing education, whereas the prevalence of MID decreased with increased education. Although this study includes only a small number of cases, necessitating some caution in interpreting the results, these figures do represent an estimate of the prevalence of severe dementing disorders and provide a basis for further community study.     

老年痴呆患者血清及脑脊液载脂蛋白E含量的变化

目的评价Ａｌｚｈｅｉｍｅｒ病（ＡＤ）及多梗塞性痴呆（ＭＩＤ）患者血清及脑脊液（ＣＳＦ）中载脂蛋白Ｅ（ａｐｏＥ）含量变化的临床意义。方法用圆周免疫扩散法测定ＡＤ１４例、ＭＩＤ１８例及对照组１８例的血清ａｐｏＥ含量，同时测定部分患者ＣＳＦ中ａｐｏＥ含量，作对比分析。结果ＣＳＦ中ａｐｏＥ含量，ＡＤ组为０．３４±０．１０ｇ／Ｌ，明显低于对照组的０．５２±０．１６ｇ／Ｌ（Ｐ＜０．０５），ＡＤ组与ＭＩＤ组（０．４３±０．０８ｇ／Ｌ）、ＭＩＤ组与对照组间差异无显著性（Ｐ＞０．０５）；血清中ａｐｏＥ在３组间差异无显著性（Ｐ＞０．０５）。结论ＣＳＦ中ａｐｏＥ含量降低对ＡＤ的诊断及鉴别诊断可能有重要意义。     

Cognitive performance correlates with cerebrovascular impairments in multi-infarct dementia

Cerebral blood flow (CBF) was measured by the 133Xe inhalation method in patients with multi-infarct dementia (MID, N = 26), Alzheimer's dementia (AD, N = 19), and among age-matched, neurologically normal, healthy volunteers (N = 26). Cognitive performance was assessed in all subjects using the Cognitive Capacity Screening Examination (CCSE). Cerebral vasomotor responses were calculated from differences in values of mean hemispheric gray matter blood flow (Delta CBF) measured during inhalation of 100% oxygen (hyperoxia) compared with CBF measured while breathing room air. Significant correlations were found between CCSE performance and vasomotor responsiveness in patients with MID (P less than .01), but not in patients with AD or in neurologically normal volunteers. Loss of vasomotor responsiveness is an indicator of cerebrovascular disease with rigidity and/or loss of reactivity of cerebral vessels, which impairs cerebrovascular responses to situational demands and predisposes to cerebral ischemia. Loss of cerebral vasomotor responsiveness among MID patients, which is a biologic marker of cerebrovascular disease, provides confirmatory evidence of the vascular etiology of MID and assists in separating MID from AD patients.     

Snoring and dementia

The frequency of snoring was studied in 46 patients with Alzheimer's disease (AD), 37 with multiinfarct dementia (MID), and in a random sample of 124 elderly community residents without known diseases affecting higher cortical functions. The demented patients were reported to snore twice as frequently as the control subjects (P less than 0.05). No difference in the frequency of snoring was present between the patients with AD and MID. In contrast to younger populations, snoring was not significantly associated with cardiovascular morbidity in this elderly population.