Behavioral correlates of cerebrospinal fluid amino acid and biogenic amine neurotransmitter alterations in dementia

BackgroundBehavioral and psychological signs and symptoms of dementia (BPSD) are a heterogeneous group of behavioral and psychiatric disturbances occurring in dementia patients of any etiology. Research suggests that altered activities of dopaminergic, serotonergic, (nor)adrenergic, as well as amino acid neurotransmitter systems play a role in the etiopathogenesis of BPSD. In this study we attempted to identify cerebrospinal fluid (CSF) neurochemical correlates of BPSD to provide further insight into its underlying neurochemical pathophysiological mechanisms.MethodsPatients with probable Alzheimer’s disease (AD; n = 202), probable AD with cerebrovascular disease (n = 37), probable frontotemporal dementia (FTD; n = 32), and probable dementia with Lewy bodies (DLB; n = 26) underwent behavioral assessment and lumbar puncture. CSF levels of six amino acids and several biogenic amines and metabolites were analyzed using ultraperformance liquid chromatography with fluorescence detection and reversed-phase high-performance liquid chromatography with fluorescence detection.ResultsIn the AD patients, CSF homovanillic acid/5-hydroxyindoleacetic acid (HVA/5HIAA) ratios correlated positively with anxieties/phobias, whereas CSF levels of taurine correlated negatively with depression and behavioral disturbances in general. In FTD patients, CSF levels of glutamate correlated negatively with verbally agitated behavior. In DLB patients, CSF levels of HVA correlated negatively with hallucinations.ConclusionsSeveral neurotransmitter systems can be linked to one specific behavioral syndrome depending on the dementia subtype. In addition to biogenic amines and metabolites, amino acids seem to play a major role in the neurochemical etiology of BPSD as well.     

The effects of behavioral and psychological symptoms on caregiver burden in frontotemporal dementia,Lewy body dementia,and Alzheimer's disease: clinical experience in China

Background and aims: Caregivers of individuals with neurodegenerative diseases, including frontotemporal dementia (FTD), Lewy body dementia (DLB), and Alzheimer's disease (AD), experience high levels of psychological and physical stress, likely due to behavioral and psychological symptoms of dementia (BPSD). This study is the first to simultaneously evaluate the effects of BPSD on caregiver burden in these three types of dementia.

Method: A total of 214 dementia patients, including probable FTD (n = 82), DLB (n = 22), and AD (n = 110), as well as their primary caregivers, were assessed using psychological inventories and cognitive evaluation. The FTD group was further divided into the three established clinical variants: behavioral variant frontotemporal dementia (bvFTD, n = 51), non-fluent variant primary progressive aphasia (nfvPPA, n = 15), and semantic variant primary progressive aphasia (svPPA, n = 16). Cognitive impairment and neuropsychiatric symptoms were assessed using the Mini Mental State Examination, Montreal Cognitive Assessment, Clock Drawing Test, and Neuropsychiatric Inventory (NPI), respectively. Caregiver burden was assessed using the Zarit Burden Inventory (ZBI).

Results: FTD patients had higher NPI and ZBI scores than DLB and AD patients, whose scores were similar. Logistic regression analysis revealed that the factors influencing caregiver burden for each group were: FTD: total NPI scores, agitation, and aberrant motor behavior; bvFTD: total NPI scores; DLB: total NPI scores; and AD: total NPI scores, onset age, apathy, and ADL. Caregivers of bvFTD patients had the highest levels of burden, which were significantly greater than for caregivers of nfvPPA, svPPA, DLB, and AD patients.

Conclusion: BPSD was highly correlated with emotional burden in caregivers of FTD, DLB, and AD patients. The highest burden was observed in bvFTD caregivers.     

Behavioral disturbances in the course of frontotemporal dementia

BACKGROUND: Behavioral disturbances are prominent in frontotemporal dementia (FTD), and their occurrence has been the topic of several investigations. Nonetheless, the prevalence and severity of behavioral disturbances of patients with FTD in different degrees of dementia severity have rarely been studied. Objective: The aim of this study was to assess and compare the prevalence and severity of behavioral disturbances in patients with mild FTD and in patients with moderate/severe dementia. METHODS: We included 21 outpatients with mild FTD [Clinical Dementia Rating (CDR) = 1] and 19 patients with moderate or severe dementia (CDR = 2 or 3) in this study. Behavioral disturbances were assessed using the Neuropsychiatric Inventory (NPI). RESULTS: We found a statistically significant difference in the total NPI scores between patients with mild FTD and patients with moderate or severe FTD, the latter scoring higher. Apathy was the most prevalent symptom in both patient groups (90.5 and 100%). Except appetite and eating disturbance, which appeared in 77.8% of the patients with moderate/severe dementia, all other symptoms were clearly less common (<50%). CONCLUSION: The results highlight the variability of behavioral disturbances in mild and moderate/severe stages of FTD.     

Neuropsychiatric symptoms of dementia: cross-sectional analysis from a prospective, longitudinal Belgian study

OBJECTIVE: Given the rather limited knowledge on profiles of neuropsychiatric symptoms (behavioural and psychological signs and symptoms of dementia, BPSD) in several degenerative dementias, we designed a prospective study of which we here present the baseline data. METHODS: Diagnosed according to strictly applied clinical diagnostic criteria, patients with probable Alzheimer's disease (AD) (n = 205), frontotemporal dementia (FTD) (n = 29), mixed dementia (MXD) (n = 39) and dementia with Lewy bodies (DLB) (n = 23) were included. All patients underwent a neuropsychological examination and behavioural assessment by means of a battery of scales (Middelheim Frontality Score (MFS), Behave-AD, Cohen-Mansfield Agitation Inventory, Cornell Scale for Depression in Dementia). RESULTS: In AD and MXD, activity disturbances and aggressiveness occurred in more than 80% of the patients. With a prevalence of 70%, apathy was very common whereas delusions and hallucinations were rare in FTD patients. Frequently used behavioural assessment scales like the Behave-AD systematically underestimated BPSD in FTD whereas the MFS displayed high sensitivity for frontal lobe symptoms. Hallucinations discriminated DLB patients from other dementias. A high prevalence of disinhibition (65%) in DLB pointed to frontal lobe involvement. CONCLUSIONS: Behavioural assessment may help differentiating between different forms of dementia, further stressing the need for the development of new and more sensitive behavioural assessment scales. By means of the MFS, frontal lobe involvement was frequently observed in DLB. As 70% of FTD patients displayed apathy, prevalence was about two times higher compared to the other disease groups, meanwhile indicating that apathy is frequently observed in dementia, irrespective of its etiology.     

The effects of abrupt antipsychotic discontinuation in cognitively impaired older persons: A pilot study

Background: Antipsychotic use for behavioural and psychological symptoms of dementia (BPSD) is controversial. Guidelines advise to reduce antipsychotics given the adverse effects and limited efficacy, to limit dose and treatment duration as well as to undertake discontinuation.

Methods: A pilot study with 40 hospitalised geriatric cognitively impaired patients, in which the effects of abrupt antipsychotic discontinuation were investigated, using neuropsychiatric inventory (NPI) scores before and one month after discontinuation. Withdrawal symptoms were monitored thrice a day with a checklist during five consecutive days.

Results: Participants (n?=?40) had a mean age of 84 years (range 67–95) and 53% were male. The total mean baseline NPI score was 21 (SD 12) with predominantly behavioural rather than psychological disturbances. After abrupt discontinuation, mild withdrawal symptoms were observed in 72% of the patients, with frequencies of symptoms peaking on day 2 (53%) and day 3 (48%). After one month, 31 patients (85%) were still off antipsychotics and improved on the majority of NPI domains, with a total mean NPI score decreasing from 18 (SD 13) to 12 (SD 8, p?=?0.003). In the relapse group, there was no deterioration associated with the abrupt discontinuation and subsequent resumption of therapy with a total mean NPI score decreasing from 31 (SD 12) at baseline to 27 (SD 8) at one-month follow-up (p?=?0.345).

Conclusion: Abrupt antipsychotic discontinuation appears to be feasible in older individuals with BPSD. Systematically performed discontinuation efforts in clinical practice are needed to differentiate between patients where antipsychotics have no added value and patients where the benefits outweigh the risks.     

The profile of behavioral and psychological symptoms in vascular cognitive impairment with and without dementia

Objective:

The objective of this study was to compare the occurrence and severity of behavioral and psychological symptoms of dementia (BPSD) between vascular dementia (VaD) and vascular cognitive impairment-no dementia (VCI-ND).

Materials and Methods:

Consecutive patients presenting with cognitive impairment at least 3 months after an ischemic stroke and with a Hachinski Ischemic Score ≥4 were included. VaD was diagnosed as per National Institute of Neurological Disorders and Stroke – Association Internationale pour la Recherche et l’Enseignement en Neurosciences criteria for probable VaD and VCI-ND on the lines of the Canadian study of health and aging. The severity of cognitive impairment and the behavioral/psychological symptoms were studied by means of the clinical dementia rating scale and the neuropsychiatric inventory (NPI) respectively.

Results:

All patients with VaD and 89% of those with VCI-ND had at least one BPSD. The mean no. of symptoms per patient and the total NPI scores were higher in VaD than in VCI-ND. Apathy and night-time behavior disturbances were significantly more common and severe in VaD.

Conclusions:

BPSD are very common both in VCI-ND and in VaD. The profile of BPSD is similar in both groups, albeit more severe in VaD. The net burden of BPSD is higher in VaD as compared to VCI-ND.Key Words: Behavioral and psychological symptoms, neuropsychiatric inventory, vascular cognitive impairment, vascular cognitive impairment-no dementia, vascular dementia     

Neuropsychiatric differences between Parkinson's disease with dementia and Alzheimer's disease

OBJECTIVE: To compare the profile of neuropsychiatric symptoms in patients with Parkinson's disease with dementia (PDD) and patients with Alzheimer's disease (AD). DESIGN: Cross-sectional survey of a population-based sample of patients with PDD and AD patients matched for age, sex, and Mini-Mental State Examination (MMSE) score. METHOD: Patients were diagnosed according to published criteria for PD and AD. The diagnosis of dementia in PD was made according to DSM-III-R, and was based on clinical interview of the patient and a relative, psychometric testing (including MMSE, Dementia Rating Scale and tests assessing memory, executive functions and visuospatial functioning) and physical examination. The Neuropsychiatric Inventory (NPI) was administered to all patients. RESULTS: One or more psychiatric symptoms was reported in 95% of AD and 83% of PDD patients. Hallucinations were more severe in PD patients, while aberrant motor behavior, agitation, disinhibition, irritability, euphoria, and apathy were more severe in AD. In PDD, apathy was more common in mild Hoehn and Yahr stages, while delusions increased with more severe motor and cognitive disturbances. In PDD, only delusions correlated with the MMSE score. CONCLUSIONS: Neuropsychiatric symptoms are common and severe in patients with PDD, with important implications for the management of these patients. AD and PDD patients have different neuropsychiatric profiles, suggesting different underlying mechanisms. Cognitive impairment, psychopathology, and motor features progress independently in PDD patients Copyright 2001 John Wiley & Sons, Ltd.     

Criminal Behavior in the Four Years Preceding Diagnosis of Neurocognitive Disorder: A Nationwide Register Study in Finland

ObjectiveTo explore the criminality of patients with subsequent diagnosis of Alzheimer's disease (AD), frontotemporal dementia (FTD), or Lewy body dementias (LBD) in the four years preceding diagnosis.DesignNationwide register study.SettingData on Finnish patients were collected from the discharge register and data on criminal offending from the police register. Research findings were compared with the same-aged general population.ParticipantsA total of 92,191 patients who had received a diagnosis of AD (N = 80,540), FTD (N = 1,060), and LBD (N = 10,591) between 1998 and 2015.MeasurementsIncidences and types of crimes, the standardized criminality ratio (number of actual crimes per number of expected crimes), and the numbers of observed cases and person-years at risk counted in five-year age groups and separately for both genders and yearly.ResultsAt least one crime was committed by 1.6% of AD women and 12.8% of AD men, with corresponding figures of 5.3% and 23.5% in FTD, and 3.0% and 11.8% in LBD. The first crime was committed on average 2.7 (standard deviation 1.1) years before the diagnosis. The standardized criminality ratio was 1.85 (95% confidence interval [CI] 1.43–2.37) in FTD women and 1.75 (95% CI 1.54–1.98) in FTD men, and in AD 1.11 (95% CI 1.04–1.17) and 1.23 (95% CI 1.20–1.27), respectively. Traffic offences and crimes against property constituted 94% of all offences.ConclusionCriminal acts may occur several years prior to the diagnosis of dementia. If novel criminality occurs later in life, it may be associated with neurocognitive disorder.     

Psychosis associated behavioral and psychological signs and symptoms in mild cognitive impairment and Alzheimer's dementia

Objectives: The aim of this study is to determine the prevalence of psychosis in mild cognitive impairment (MCI, Petersen's criteria) and patients with Alzheimer's dementia, and to characterize the associated behavioral and psychological signs and symptoms of dementia (BPSD).

Method: A cross-sectional analysis of baseline data from an ongoing, prospective, longitudinal study on BPSD was performed, including 270 MCI and 402 AD patients. BPSD assessment was performed through Middelheim Frontality Score (MFS), Behave-AD, Cohen-Mansfield Agitation Inventory (CMAI) and Cornell Scale for Depression in Dementia (CSDD). Psychosis was considered to be clinically relevant when delusions and/or hallucinations occurred at least once in the last two weeks prior to the BPSD assessment.

Results: The prevalence of psychosis in AD (40%) was higher than in MCI (14%; p < 0.001). AD patients with psychosis showed more severe frontal lobe, BPSD, agitation and depressive symptoms (MFS, Behave-AD, CMAI and CSDD total scores), whereas MCI patients with psychosis only showed more severe frontal lobe and physically non-aggressive agitated behavior. In addition, only in psychotic AD patients, all BPSD and types of agitation were more severe compared to non-psychotic AD patients. Comparing MCI and AD patients, MCI patients with psychosis did not show more severe frontal lobe, behavioral and psychological (Behave-AD), depressive symptoms or agitation than AD patients without psychosis.

Conclusion: AD patients clearly display psychosis associated BPSD, whereas MCI patients only display more severe frontal lobe symptoms and physically non-aggressive agitated behavior, but also less pronounced than in AD.     

Successful treatment with Yokukansan for behavioral and psychological symptoms of Parkinsonian dementia

Objective

To evaluate the efficacy and safety of Yokukansan, a traditional Chinese herbal medicine, for treating behavioral and psychological symptoms of dementia (BPSD) in patients with Parkinson disease (PD; n = 7) and those with PD with dementia (PDD; n = 7).

Background

BPSD are often seen in patients with senile dementia and have serious deleterious effects on the lives of patients and caregivers. Recent studies indicate that the traditional Chinese herbal medicine Yokukansan may be safe and beneficial for the treatment of BPSD patients.

Methods

We treated 7 PD and 7 PDD patients for 4 weeks with Yokukansan and observed them without Yokukansan for 4 weeks. Changes in behavioral and psychological symptoms were evaluated every 4 weeks according to the Neuropsychiatric Inventory (NPI) scale.

Results

Significant improvements in behavioral and psychological symptoms, particularly in the incidence and duration of hallucinations, were observed in most PD and PDD patients after 4 weeks of Yokukansan treatment. No significant changes were observed in the laboratory tests, cognitive function, activities of daily living, or parkinsonism.

Conclusion

Our results suggest that Yokukansan improves BPSD in both PD and PDD patients without worsening their cognitive function, ability to perform activities of daily living, or parkinsonism.     

阿尔茨海默病精神行为症状复发的危险因素和特征

目的探讨阿尔茨海默病(Alzheimer's disease,AD)患者精神行为症状(behavioral and psychologicalsymptoms of dementia,BPSD)复发的危险因素和特征。方法收集102例以BPSD发作就诊的AD患者,在BPSD发作控制后进行12个月的随访。BPSD的严重程度应用神经精神量表(neuropsychiatric inventory,NPI)评估,并将NPI因子归类为情感障碍、精神病性症状和失控行为3个症状群。分析BPSD复发与先前发作的特征,复发与患者人口学资料、发病年龄、病程、认知功能、日常生活能力、基线NPI评分等因素的关系。结果 12个月内44.1%(45/102)的患者BPSD复发。Cox回归分析显示,环境改变(RR=5.42,P<0.05)、未维持服药(RR=3.13,P<0.05)和上次发作NPI评分高(RR=1.06,P<0.05)增加BPSD复发的风险;两次BPSD发作之间的症状数相关(r=0.93,P<0.05),而情感障碍评分也相关(r=0.79,P<0.05);复发的NPI总分和精神病性症状评分均低于上次发作[(18.29±2.0...     

Efficacité d’une unité cognitivo-comportementale sur les symptômes psychologiques et comportementaux des démences

IntroductionCognitive-behavioral units (CBUs) have been created in the context of the national Alzheimer plan 2008/2012 for the management of behavioral disorders of patients suffering from Alzheimer's disease or related diseases. The Alzheimer plan promotes the evaluation of these units through the observation of the evolution of behavioral and psychological symptoms of dementia (BPSD). The aim of this study was to assess the effects of the memory center of Lyon (hospices civils de Lyon) CBU on BPSD.PatientsThe neuropsychiatric inventory (NPI) was rated by the patients’ caregiver (NPI-F) at admission to the CBU and 2 weeks after the discharge. The NPI was also rated by the nursing staff (NPI-NS) 3 days after admission in the CBU and at discharge.ResultsAll patients admitted in the CBU between July and October 2001 were included in the study for a total of 28 patients. A significant reduction of NPI-F scores between admission (58.93 ± 24.8) and 2 weeks after the discharge (27.07 ± 19.70) (P < 0.0001) was observed. Improvement was specifically observed for delusions, agitation, depression, anxiety, disinhibition and aberrant motor activity symptoms. No significant changes were found on NPI-NS scores.ConclusionThis study discloses benefits of CBUs in terms of BPSD reduction in patients 2 weeks after CBU discharge. These units have the potential to achieve their principal objective of reducing behavioral problems.     

Neuropsychiatric symptoms in dementia-frequency, relationship to dementia severity and comparison in Alzheimer's disease, vascular dementia and frontotemporal dementia

Noncognitive behavioral and psychiatric disturbances are common in dementia and help in the clinical differentiation of the various subtypes. We studied the frequency of neuropsychiatric disturbances, their relationship to dementia severity and compared these disturbances in Alzheimer's disease (AD), vascular dementia (VaD) and frontotemporal dementia (FTD) using the 12-item Neuropsychiatric Inventory (NPI). A total of 98 patients (AD-44, VaD-31, FTD-23) were evaluated. All subjects were community dwelling at the time of evaluation. The three groups were comparable on global dementia severity and functional ability. All patients had clinically significant scores on the NPI with apathy, irritability and agitation being very common (>90% of patients). AD and VaD patients in Clinical Dementia Rating (CDR) stage 2 had significantly higher scores on the total NPI, agitation and disinhibition subscales compared to those in CDR stage 1. Mean scores in the domains of aberrant motor behavior, disinhibition and appetite/eating behavior differentiated FTD from AD and VaD. Neuropsychiatric disturbances in dementia appear to be universal with agitation, disinhibition and irritability being more frequent in the later stages. In this cohort disinhibition, aberrant motor behavior and appetite/eating disturbances could reliably differentiate AD and VaD from FTD. There were no significant differences between the neuropsychiatric profiles of AD and VaD.     

Grouping and trajectories of the neuropsychiatric symptoms in patients with Alzheimer's disease, part I: symptom clusters

Behavioral and psychological symptoms of dementia (BPSD) are frequently observed in Alzheimer's disease (AD) and affect more than 80% of patients over the course of AD. The goal of this study was to establish a model for grouping the symptoms of BPSD into clinical syndromes. Over a 24-month period, an observational study was conducted using a population of ambulatory patients with AD of mild to moderate severity. The Neuropsychiatric Inventory (NPI) was administered to the patients' caregivers every 6 months. BPSD were grouped using exploratory factor analysis (EFA) and confirmatory factor analysis (CFA) of the NPI scores of each assessment. The sample population consisted of 491 patients (70.9% women) with an average age of 75.2 years (SD=6.6). The five EFA suggested that there was a stable three-factor structure. According to the results of the EFA, three models of symptom grouping were adjusted using CFA methodology. The CFA model that satisfactorily grouped the NPI scores into three factors included a psychotic syndrome (hallucinations, delusions), an affective syndrome (depression, anxiety, irritability, agitation) and a behavior syndrome (euphoria, disinhibition, apathy, aberrant motor behavior). Based on our findings, we propose a model for grouping the BDSD in which there are core nuclear syndromes (psychotic and affective) as well as an unspecified behavior syndrome comprising satellite symptoms that may be related to the presence of the nuclear syndromes.     

The Behavioral Effects of Combination Therapy of Memantine and Acetylcholinesterase Inhibitors Compared with Acetylcholinesterase Inhibitors Alone in Patients with Moderate Alzheimer’s Dementia: A Double-Blind Randomized Placebo-Controlled Trial

Objective This study aimed to investigate treatment effects of combination therapy of memantine and acetylcholinesterase inhibitors (AchEIs) compared with AchEIs alone on behavioral and psychological symptoms of dementia (BPSD) in patients with moderate Alzheimer’s dementia (AD). Methods This was a 12-week, double-blind, randomized, placebo-controlled trial. A total of 148 patients with moderate AD participated in this study. Mini-Mental State Examination, Neuropsychiatric Inventory (NPI), Clinician’s Interview-Based Impression of Change plus caregiver input, Gottfries–Bråne–Steen Scale, and Zarit Burden Interview were used as assessment scales. Results There were no significant differences in age, sex, or education between AChEIs alone and combination groups. The combination group showed significantly more improvement of NPI-disinhibition score (0.76±2.15) than the AChEIs alone group (-0.14±1.71) after 12 weeks. Conclusion Our findings suggest that the combination therapy of memantine and AchEIs might be a beneficial option for reducing disinhibition symptoms of patients with moderate AD compared with AchEIs alone. We believe that clinicians need to consider additional memantine treatment when patients with moderate AD complain disinhibition symptom. A larger clinical trial is needed to further determine the efficacy and advantages of such combination therapy of memantine and AchEIs for treating BPSD of patients with moderate AD.     

The ABC of Alzheimer's disease: behavioral symptoms and their treatment

Behavioral and psychological symptoms of dementia (BPSD) are a common manifestation of Alzheimer's disease (AD) and other dementia syndromes. Patients experience prominent and multiple symptoms, which are both distressing and a source of considerable social, health, and economic cost. Development of symptoms is in part related to progressive neurodegeneration and cholinergic deficiency in brain regions important in the regulation of behavioral and emotional responses including the cortex, hippocampus, and limbic system. Cholinesterase (ChE) inhibitors offer a mechanism-based approach to therapy to enhance endogenous cholinergic neurotransmission. Studies using ChE inhibitors have demonstrated their clear potential to improve or stabilize existing BPSD. Differences have been noted between selective acetylcholinesterase (AChE) inhibitors (donepezil and galantamine) and dual ChE inhibitors (rivastigmine) in terms of treatment response. While donepezil has shown efficacy in moderate to severe noninstitutionalized AD patients, conflicting results have been obtained in mild to moderate patients and in nursing home patients. Galantamine has been shown to delay the onset of BPSD during a five-month study but has been otherwise poorly studied to-date. Both donepezil and galantamine have not as yet demonstrated efficacy in reducing psychotic symptoms or in reducing levels of concomitant psychotropic medication use. Studies with the dual ChE inhibitor rivastigmine in mild to moderately severe AD and in Lewy body dementia (LBD) have shown improvements in behavioral symptoms including psychosis. Improvements have been maintained over a period of up to two years. In addition, institutionalized patients with severe AD have shown symptomatic benefits with a reduction in the requirement for additional psychotropic drugs following treatment with rivastigmine. The psychotropic properties associated with rivastigmine may in part be mediated through effects on butyrylcholinesterase. Current treatment options are limited for patients with dementia syndromes other than AD. However, data concerning rivastigmine in patients with LBD and preliminary studies in Parkinson's disease dementia and vascular dementia suggest a role for ChE inhibitors across the spectrum of dementia syndromes. Finally, studies that incorporated a delayed start design demonstrate that ChE inhibitors may delay the progression of BPSD.     

Behavioural and psychological symptoms of Alzheimer type dementia are not correlated with plasma homocysteine concentration

BACKGROUND/AIMS: Vitamin B12 and folate deficiencies have been associated with cognitive impairment and various psychiatric symptoms but not specifically with behavioural and psychological symptoms of dementia (BPSD). A limitation of previous studies in dementia was lack of concurrent homocysteine measurement especially as it may provide a better indicator of tissue activities of these vitamins. This study was designed to clarify whether a relationship exists between plasma homocysteine concentration and BPSD. METHODS: Plasma homocysteine, serum vitamin B12 and folate were measured in 23 Alzheimer's disease (AD) patients with BPSD and 27 AD patients without BPSD as determined through the use of the Neuropsychiatric Inventory (NPI). Blood levels of measured substances were also correlated with individual NPI scores and with cumulative NPI scores for different cluster of symptoms. RESULTS: There was no significant difference (p = 0.956) in the mean plasma homocysteine levels between AD patients with BPSD (17.48 micromol/l) and AD patients without BPSD (17.34 micromol/l). Similarly, there was no significant difference between the two groups in the mean serum B12 (382.61 and 391.60 pg/ml, respectively) and folate (7.95 and 10.02 ng/ml, respectively). Mean levels for both vitamins were well within the laboratory reference range. Neither individual nor cluster NPI scores correlated significantly with plasma homocysteine. CONCLUSION: This study shows for the first time that BPSD are not associated with hyperhomocysteinaemia in Alzheimer dementia. Although previous studies have identified homocysteine as an independent risk factor in AD, the results reported here do not lend weight to an aetiological role for homocysteine specifically in BPSD.     

Prevalence and severity of behavioral and psychological symptoms of dementia (BPSD) in community dwelling Chinese: findings from the Shanghai three districts study

Objectives: Studies of the prevalence and risk factors for behavioral and psychological symptoms of dementia (BPSD) have primarily been conducted in nursing home and clinic populations. Few population-based studies have been conducted in community-living persons with dementia.

Methods: In this cross-sectional study, persons aged 65 and above who were living in the community were screened for dementia with the Chinese version of Mini-Mental State Examination (CMMSE) and Ability of Daily Living (ADL-14) scale. Participants with a diagnosis of dementia according to DSM-IV criteria made by trained neuropsychiatrists s were with the Neuropsychiatric Inventory assessed for BPSD by informant interview.

Results: Among 1271 persons with dementia, 50.1% had at least one BPSD. Sleep disturbance was the most common symptom (21.9%), followed by irritability (19.6%), and apathy (15.7%). About 40% (N = 501) of these problems were clinically significant (NPI score > 4). The NPI score was significantly associated with the CMMSE score, ADL score and education.

Conclusion: BPSD are common among community living Chinese people with dementia, but the relatively lower prevalence rate and different pattern of symptoms from those reported in the USA, UK and Japan suggest the possible influence of cultural background and psychosocial environment.     

Neuropsychiatric symptoms of progressive supranuclear palsy in a dementia clinic

Background: Progressive supranuclear palsy (PSP) is a neurodegenerative disease characterized by supranuclear gaze palsy, postural instability, akinesia and other parkinsonism. Recently, the relationship between PSP and frontotemporal dementia (FTD) has been recognized, which includes clinical, pathological, biochemical and genetic features. However, there have been few studies that directly compared neuropsychiatric symptoms between PSP and FTD. The aim of the present study was to investigate comprehensive psychiatric and behavioural symptoms in PSP and compared them with those in FTD. Methods: Patients with PSP (n = 10) and FTD (n = 13) were selected on the basis of inclusion/exclusion criteria from a consecutive series in the dementia clinic of Kumamoto University Hospital. We assessed their comprehensive neuropsychiatric features by using the Neuropsychiatric Inventory (NPI), the Stereotypy Rating Inventory (SRI) and a specific antisocial behaviour checklist. Results: There were no significant differences in the total NPI and NPI subscale scores between the two groups. Both groups showed quite a similar pattern in the features of neuropsychiatric symptoms: apathy showed the highest score, followed by aberrant motor behaviour and disinhibition. The PSP group was significantly lower in the total SRI and eating and cooking behaviour scores than those in the FTD group. The prevalence of antisocial behaviours in PSP (50%) was equal to those in the FTD group (46%). Conclusions: In a dementia clinic, the neuropsychiatric profile in patients with PSP closely resembled those in the FTD group. The present results suggest that PSP should be considered as not only a movement disorder, but also a disorder with a wide range of neuropsychiatric symptoms.     

Frontotemporal dementia: behavioral symptoms and caregiver distress

OBJECTIVE: To discern behavioral problems that co-occur in frontotemporal dementia (FTD) patients, and to investigate the relation between behavioral clusters and the burden for caregivers. PATIENTS AND METHODS: Baseline data of 63 FTD patients and their respective caregivers were used to detect the behavioral clusters in the Neuropsychiatric Inventory (NPI) and the accompanying distress evoked in caregivers. To detect the clusters in behavior of the FTD patients, we performed multidimensional scaling (procedure: PROXSCAL). Multiple regression analysis was used to determine the association between behavior of patients and the distress experienced by caregivers. RESULTS: This was the first study that found behavioral clusters for FTD. Two behavioral clusters were found: agitation/psychosis (comprising delusions, hallucinations, irritability and agitation) and mood (made up of anxiety and depression). The remaining NPI domains (euphoria, disinhibition, aberrant motor behavior and apathy were found to be autonomous. After controlling for relevant confounding factors, caregiver distress was strongest related to agitation/psychosis, followed by mood. Disinhibition and aberrant motor behavior were mildly related to caregiver distress. Euphoria and apathy were not significantly related to distress. Caregivers of patients living at home were more distressed by the behavioral problems of the FTD patients than caregivers of hospitalized patients. DISCUSSION: The high prevalence of psychopathology in FTD patients and the associated caregiver distress was confirmed in this study. Clustering behavioral symptoms allows investigation of the relationship between structural or functional cerebral deficits and neuropsychiatric symptoms.