Behavioral and psychological symptoms of dementia characteristic of mild Alzheimer patients

In order to clarify the characteristics of Behavioral and Psychological Symptoms of Dementia (BPSD) in patients with mild Alzheimer's disease (AD), BPSD among the severities of Clinical Dementia Rating (CDR) in 74 patients with AD were compared using the Neuropsychiatric inventory (NPI). The result, when compared between mild (CDR = 0.5, 1) and moderate or severe (CDR = 2, 3) AD, was a significant difference in frequency of euphoria, disinhibition and aberrant motor behavior, but no significant difference was found in frequency of delusions, hallucinations, agitation, dysphoria, anxiety, apathy and irritability. In addition, a significant difference was found in the mean scores of the composite score for euphoria, apathy, disinhibition and aberrant motor behavior, but no significant difference was found in the mean scores of the composite score for delusions, hallucinations, agitation, dysphoria, anxiety and irritability. That is, the mild AD groups (CDR 0.5 or 1) had delusions, hallucinations, agitation, dysphoria, anxiety, apathy and irritability as frequently as the moderate or severe AD groups (CDR 2 or 3), and had the equivalent level of composite scores to the moderate or severe AD groups (CDR 2 or 3) in delusion, hallucination, agitation, dysphoria, anxiety and irritability. Therefore, it was supposed that psychotic symptoms (delusion, hallucination) and emotional symptoms (agitation, dysphoria, anxiety, irritability) are important BPSD in patients with mild AD as well as those with moderate or severe AD, and there are needs for health, welfare and medical services for these symptoms.     

Efficacy of metrifonate in improving the psychiatric and behavioral disturbances of patients with Alzheimer's disease.

Neuropsychiatric and behavioral symptoms are frequent and problematic components of Alzheimer's disease (AD). In two previously reported studies, metrifonate was shown to benefit behavioral symptoms as assessed by the Neuropsychiatric Inventory (NPI). In this post hoc analysis, detailed studies were completed to determine the effects of metrifonate on individual symptoms. This study was a retrospective analysis of pooled NPI data from two double-blind, placebo-controlled, multicenter 26-week studies of metrifonate that had achieved similar levels of cholinesterase inhibition. Mild-to-moderate probable AD patients received placebo (n = 222) or metrifonate (n = 450) 30 to 60 mg by weight or a 50-mg fixed dose once daily. At 26 weeks, metrifonate-treated patients had significantly reduced NPI total scores (P = .001) and fewer neuropsychiatric symptoms when compared with placebo-treated patients, including hallucinations (P = .004), agitation/aggression (P = .006), depression/dysphoria (P = .011), apathy (P = .019), and aberrant motor behavior (P = .008). Metrifonate reduced or stabilized neuropsychiatric disturbances in 60% of symptomatic patients. Almost 40% of metrifonate-treated patients had a clinically relevant reduction (> or = 30% decrease in NPI score) in their neuropsychiatric disturbances (P = .002). High proportions of metrifonate-treated patients manifested clinically relevant reductions in anxiety (58%, P = .009), apathy (51%, P = .020), and depression/dysphoria (50%, P = .021) compared to placebo. The metrifonate-associated reductions in NPI scores were evident by week 12 and were maintained for the 26-week study period. There was an overall effect size of metrifonate of approximately 15% on total NPI scores when compared to placebo. Metrifonate significantly reduced many of the psychiatric and behavioral symptoms of AD. The observations suggest that enhancement of cholinergic functions in AD has beneficial effects on behavior.     

Neuropsychiatric Symptoms and Global Functional Impairment along the Alzheimer's Continuum

Background/Aims: Neuropsychiatric symptoms in Alzheimer's disease (AD) are highly prevalent. We sought to determine whether neuropsychiatric symptoms were related to global functional impairment at baseline and over a 3-year period in older normal control (NC), mild cognitive impairment (MCI) and mild AD dementia subjects. Methods: Eight hundred and twelve subjects (229 NC, 395 MCI, 188 AD) from the Alzheimer's Disease Neuroimaging Initiative study underwent cognitive and behavioral assessments over 3 years. Results: Greater hallucinations, anxiety and apathy were associated with greater global functional impairment at baseline, while the presence of hallucinations and apathy at baseline was associated with greater global functional impairment over time across all subjects. The following neuropsychiatric symptoms were not significantly associated with global functioning: delusions, agitation, depression, euphoria, disinhibition, irritability, aberrant motor behaviors, sleep and appetite. Conclusions: These results suggest that increased baseline hallucinations, apathy and anxiety are associated with current and future disease progression in AD.     

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.     

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.     

Impact of behavioral subsyndromes on cognitive decline in Alzheimer’s disease: data from the ICTUS study

Behavioral and psychological symptoms of dementia (BPSD) represent common manifestations among patients affected by Alzheimer’s disease (AD). Some reports have recently classified BPSD into specific clusters/subsyndromes exploring the internal structure of the Neuropsychiatric Inventory (NPI). We evaluated whether specific behavioral subsyndromes are associated with worsening cognitive function. Mild to moderate AD patients were recruited from the cohort of the Impact of Cholinergic Treatment USe (ICTUS) study. Neuropsychiatric symptoms were classified in three subsyndromes, identified at baseline, grouping different combinations of NPI items: (1) “psychotic” (“delusions” and/or “hallucinations”); (2) “affective” (“agitation” and/or “depression” and/or “anxiety” and/or “irritability”); and (3) “behavioral” (“euphoria” and/or “apathy” and/or “disinhibition” and/or “aberrant motor behavior”). Mixed model analyses were performed to measure six-monthly changes in the ADAS-Cog score over a follow-up of 2 years, according to these subsyndromes. All analyses were stratified according to AD severity as defined by the Clinical Dementia Rating (CDR). A total of 1,375 AD subjects were recruited. No NPI cluster was found to significantly (p < 0.05) affect the rate of cognitive decline across the 3 CDR classes. Our results suggest that the cognitive course of AD is not substantially influenced by the presence of specific neuropsychiatric phenotypes. Further studies are needed to extend the present findings and identify possible biological and clinical bases for behavioral subsyndromes.     

Efficacy of donepezil on behavioral symptoms in patients with moderate to severe Alzheimer's disease

OBJECTIVE: This subanalysis of a large, double-blind, placebo-controlled trial examined the prevalence of behavioral symptoms in moderate to severe Alzheimer's disease (AD), and the effect of treatment with donepezil. METHODS: Two hundred ninety patients with moderate to severe AD (standardized Mini-Mental State Examination scores 5-17) were randomized to receive 24 weeks of once-daily doses of donepezil 5 mg/day for 28 days, and 10 mg/day thereafter per the clinician's judgment (n = 144), or placebo (n = 146). The outcome measure of interest was the 12-item Neuropsychiatric Inventory (NPI). RESULTS: Baseline demographics were similar between the treatment groups. Least squares mean (+/- SE) baseline NPI 12-item total scores were 19.55 +/- 1.48 and 19.30 +/- 1.45, respectively. At baseline, the most common symptoms were apathy/indifference (67%), aberrant motor behavior (53%), depression/dysphoria (52%), anxiety (49%), and agitation/aggression (45%). NPI individual item change from baseline scores at Week 24 using a last observation carried forward (LOCF) analysis showed benefits with donepezil treatment compared with placebo for all items, with significant treatment differences for depression/dysphoria, anxiety, and apathy/indifference (p < .05). Symptoms present at baseline that improved significantly for donepezil- compared with placebo-treated patients at Week 24 LOCF included anxiety, apathy/indifference, and irritability/lability (p < .05). When patients who were not receiving psychoactive medications at baseline were analyzed separately, significant improvements in NPI (continued) 12-item total score were observed with donepezil compared with placebo at most visits and at Week 24 LOCF (p < .05). CONCLUSIONS: Behavioral symptoms of the magnitude observed in this moderate to severe AD population improved with donepezil.     

Grouping and trajectories of neuropsychiatric symptoms in patients with Alzheimer's disease. Part II: two-year patient trajectories

Behavioral and psychological symptoms of dementia (BPSD) are characterized by fluctuations in their frequency and severity as well as by differences in the concurrent presentation of different symptoms. The goal of the current study was to identify groups of patients with Alzheimer's disease (AD) that had similar trajectories in the expression of BPSD. Over a 24-month period, an observational study was conducted using a population of ambulatory patients with AD of mild or moderate severity. The Neuropsychiatric Inventory (NPI) was administered every 6 months to the patient's caregiver. To classify patients according to changes in the frequency and severity of BPSD, growth mixture models were fitted to the applied to the grouping of NPI subscales in the following three categories: psychotic syndrome (hallucinations and delusions), affective syndrome (depression, anxiety, irritability, and agitation), and behavioral syndrome (disinhibition, euphoria, apathy, and aberrant motor behavior). The sample population consisted of 491 patients (70.9% women) that had an average age of 75.2 years (SD=6.6). Different trajectory patterns were identified based on differences in changes over the time in the frequency (stable, increasing, decreasing, or fluctuating in course) and severity (low, moderate, or elevated severity) for psychotic syndrome, emotional syndrome, and behavior syndrome. Patients with AD display a high degree of variability in the evolutionary course of BPSD. It is possible to identify groups of patients with similar evolutionary trajectories in terms of changes in the frequency and severity of BPSD.     

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.     

Risk factors for neuropsychiatric symptoms in dementia: the Cache County Study

OBJECTIVE: To investigate the probability of individual neuropsychiatric symptoms in dementia patients as a function of eight risk factors. METHODS: In the Cache County Study, we administered the Neuropsychiatric Inventory (NPI) to 328 dementia patients at baseline. Approximately 18 months later, we re-administered the NPI to 184 participants available for follow-up. Generalized estimating equation methods were used to model the probability of individual neuropsychiatric symptoms as a function of: gender, age, education, dementia type and severity, APOE status, time of observation, and general medical health. RESULTS: Women showed increased tendency toward anxiety, [odds ratio (OR) 2.22, 95% confidence interval (CI) 1.31-3.76] and delusions (OR 2.15, CI 1.22-3.78), but older persons of both sexes showed less tendency toward anxiety. Dementia severity increased the tendency toward hallucinations and agitation (OR 2.42, CI 1.81-3.23) and decreased risk of depression. Positive APOE epsilon4 status increased the tendency toward aberrant motor behavior (OR 1.84, CI 1.05-3.22). Among dementia diagnoses, those with Alzheimer's disease showed decreased tendency toward agitation (OR 0.58, CI 0.35-0.95), depression (OR 0.56, CI 0.33-0.96) and disinhibition (OR 0.46, CI 0.24-0.88). Later time of observation increased risk of aberrant motor behavior and delusions, and more serious medical comorbidity increased risk of, agitation, irritability, disinhibition, and aberrant motor behavior. CONCLUSIONS: Gender, age, dementia severity, APOE epsilon4, dementia diagnosis, time of observation, and general medical health appear to influence the occurrence of individual neuropsychiatric symptoms.     

An exploratory study of the efficacy and safety of yokukansan for neuropsychiatric symptoms in patients with Parkinson’s disease

The present study examined the efficacy and safety of yokukansan (YKS) in neuropsychiatric symptoms in patients with Parkinson’s disease (PD) using the neuropsychiatric inventory (NPI). Twenty-five patients with PD (M:F 14:11; age 72 years) were enrolled and treated with YKS (7.5 g/day) for 12 weeks. The NPI was assessed at 0, 4, 8, 12 and 16 weeks. The patient’s motor function and progression were evaluated using the Unified PD Rating Scale part III (UPDRS-III) and Hoehn and Yahr scale, respectively. The serum potassium concentration (sK) and all adverse events were recorded. The median NPI total score significantly decreased from 12 points at baseline to 4.0 points at 12 weeks (p = 0.00003). Within each NPI subscale, significant improvements were observed in hallucinations, anxiety and apathy. These symptoms tended to worsen after the completion of YKS treatment. Delusions, agitation, depression, euphoria, disinhibition, aberrant motor activity tended to improve but irritability showed no change. The median NPI subtotal scores, positive symptoms (delusions–hallucinations–irritability) significantly decreased (p = 0.01660) and negative symptoms (anxiety–apathy) significantly decreased (p = 0.00391). Both UPDRS-III and the Hoehn and Yahr scale showed no significant change. sK decreased mildly from 4.26 ± 0.30 to 4.08 ± 0.33 mEq/L. Two patients showed hypokalemia lower than 3.5 mEq/L without any corresponding symptoms; two patients showed listlessness and one patient showed drug eruption. Each recovered after discontinuation of YKS. YKS improved neuropsychiatric symptoms associated with PD, including hallucinations, anxiety and apathy without severe adverse events and worsening of Parkinsonism.     

Apolipoprotein E genotype influences presence and severity of delusions and aggressive behavior in Alzheimer disease

AIM: We investigated differences in the prevalence and severity of 10 neuropsychiatric and behavioral symptoms according to apolipoprotein E (APOE) genotype and dementia severity in Alzheimer disease (AD). METHODS: Neuropsychiatric and behavioral symptoms of 110 AD patients were assessed using the Neuropsychatric Inventory. Dementia severity was assessed using the Mini Mental State Examination (MMSE). RESULTS: There were 27 APOE-epsilon4-negative patients, 65 heterozygous patients and 18 homozygous patients. There was a significant association between the number of APOE epsilon4 alleles and prevalence and severity of neuropsychiatric and behavioral symptoms that was mainly attributable to delusions and agitation/aggression, which were more common and severer among homozygous APOE epsilon4 carriers. In addition, the presence of hallucinations, anxiety, apathy and aberrant motor behavior increased with deteriorating MMSE score, independently of APOE epsilon4 status. CONCLUSIONS: The present study showed that the APOE epsilon4 genotype modifies neuropsychiatric and behavioral phenotype in AD. In particular, it was shown that delusions and agitation/aggression were more common and severer among homozygous APOE epsilon4 carriers than among heterozygous or APOE-epsilon4-negative patients.     

Role of Donepezil in the Management of Neuropsychiatric Symptoms in Alzheimer's Disease and Dementia with Lewy Bodies

Alzheimer's disease (AD) is a progressive condition that affects cognition, function, and behavior. Approximately 60–90% of patients with AD develop neuropsychiatric symptoms (NPS) such as hallucinations, delusions, agitation/aggression, dysphoria/depression, anxiety, irritability, disinhibition, euphoria, apathy, aberrant motor behavior, sleep disturbances, appetite and eating changes, or altered sexual behavior. These noncognitive behavior changes are thought to result from anatomical and biochemical changes within the brain, and have been linked, in part, to cholinergic deficiency. Cholinesterase inhibitors may reduce the emergence of NPS and have a role in their treatment. These agents may delay initiation of, or reduce the need for, other drugs such as antipsychotics. This article summarizes the effects of donepezil, a cholinesterase inhibitor, on the NPS of dementia with emphasis on AD and dementia with Lewy bodies.     

Mild cognitive impairment is associated with characteristic neuropsychiatric symptoms

Mild cognitive impairment (MCI) has emerged as an identifiable condition and in many cases is a transitional state preceding diagnosable Alzheimer disease (AD). Neurobiological and neuroimaging characteristics of amnestic-type MCI have been investigated, but few comprehensive neuropsychiatric studies have been reported. The aim of this preliminary study was to define the neuropsychiatric features of the amnestic-type MCI and compare them with those of mild AD and normal controls. The Neuropsychiatric Inventory (NPI) was used to assess the neuropsychiatric symptoms in three age and education comparable groups, i.e., 28 MCI, 124 mild AD, and 50 normal subjects. Individual subscores of the 10 NPI symptoms and total NPI scores were compared between the MCI patients and the other 2 groups. The results of this preliminary investigation showed that MCI patients frequently manifested neuropsychiatric symptoms. The most common symptoms in the MCI group were dysphoria (39%), apathy (39%), irritability (29%), and anxiety (25%). There were significant differences in apathy, dysphoria, irritability, anxiety, agitation, and aberrant motor behavior between the MCI and control groups; in contrast, only delusions were significantly less common in MCI compared with mild AD. There was a significant difference between the MCI and control groups on total NPI scores (p = 0.001), but not between the MCI and mild AD groups (p = 0.304). Amnestic MCI is associated with significant neuropsychiatric symptoms, especially mood disturbances and apathy. Psychotic symptoms are significantly more common in the early stage of AD than in MCI. These results are derived from a limited clinical sample and require confirmation in longitudinal community-based investigations.     

Caregiver burden associated with behavioral and psychological symptoms of dementia in elderly people in the local community

BACKGROUND: Despite many studies about the association between caregiver burden and behavioral and psychological symptoms of dementia (BPSD), there have been no population-based studies to evaluate caregiver burden associated with each BPSD. OBJECTIVE: To evaluate caregiver burden associated with the individual BPSD in elderly people living in the community. METHODS: The subjects were 67 participants with dementia living with their caregivers (diagnosed in the third Nakayama study): 51 Alzheimer's disease, 5 vascular dementia and 11 other. The Neuropsychiatric Inventory (NPI) and NPI Caregiver Distress Scale (NPI-D) were used to assess subjects' BPSD and related caregiver distress, respectively. RESULTS: In the subjects exhibiting BPSD, aberrant motor behavior had the highest mean NPI score, and depression/dysphoria had the lowest. Agitation/aggression had the highest mean NPI-D score, and euphoria/elation had the lowest. Delusion, agitation/aggression, apathy/indifference, irritability/lability and aberrant motor behavior showed a correlation between the NPI and NPI-D scores. CONCLUSION: The burden associated with BPSD is different for each symptom and does not always depend on frequency and severity of BPSD. These findings suggest that some symptoms, such as agitation/aggression and irritability/lability, may affect the caregivers significantly, although their frequency and severity are low.     

Determinants of the quality of life in Alzheimer's disease patients as assessed by the Japanese version of the Quality of Life-Alzheimer's disease scale

BACKGROUND: Although QOL is an important indicator to assess multiple facets of life, the QOL of Alzheimer's disease (AD) subjects with impaired cognitive ability due to dementia has not yet been fully investigated. In this study, we developed the Japanese version of the Quality of Life-Alzheimer's disease (QOL-AD) scale by means of back-translation, and ascertained its reliability and validity for evaluating the quality of life in AD subjects. We also hypothesized that the presence of neuropsychiatric symptoms may determine the characteristics and determinants of both the patients' and the caregivers' responses to the patients' QOL questionnaire. METHODS: We administered the QOL-AD questionnaire to subjects with mild or moderate AD (n = 140). The test-retest reliability was evaluated by the same interviewer after a month's interval. Data from the following tests were also collected to ascertain the validity of the questionnaire: Short Memory Questionnaire (SMQ), Neuropsychiatry Inventory (NPI), Hyogo Activities of Daily Living Scale (HADL) and Mini-Mental State Examination (MMSE). RESULTS: The Japanese version of the QOL-AD questionnaire demonstrated good internal reliability for both the patients' (Cronbach's alpha = 0.84) and the caregivers' responses (Cronbach's alpha = 0.82) and good test-retest reliability for both the patients' (intraclass correlation coefficient = 0.84) and caregivers' reports (intraclass correlation coefficient = 0.91). The concordance between the patients' self-report and the caregivers' observation was moderate (Pearson correlation coefficient = 0.60). The score for the 'mood factor' (apathy, depression/dysphoria) in NPI predicted the overall QOL score as determined from both the patients' and the caregivers' responses for subjects with mild (MMSE>or=21, n = 88) and moderate (MMSE< 21, n = 52) AD. The score for the 'psychosis factor' (delusions, hallucinations, anxiety, agitation, disinhibition, irritability, aberrant motor activity) in NPI predicted the total QOL score as determined by the patients and the caregivers among subjects with moderate AD only. CONCLUSIONS: As hypothesized, the presence of neuropsychiatric symptoms may be an important predictor of both the patients' and caregivers' responses to the patients' QOL questionnaire. QOL-AD appears to be a promising measure of the QOL of subjects with mild to moderate AD in Japan.     

血管性痴呆精神行为学症状的相关因素分析

目的 了解血管性痴呆(VaD)患者的精神行为学症状特点及与认知障碍、年龄、受教育程度等因素的相关性,探讨神经精神科问卷(NPI)中不同因子之间的内在联系. 方法 采用NPI和简易智能状态检查量表(MMSE),分别评价120例VaD患者和61例健康老年人的精神行为学症状. 结果 VaD组患者NPI量表中的妄想、幻觉、激越、抑郁/心境恶劣、淡漠、易激惹、异常行为、食欲和饮食障碍等8个症状得分均明显高于正常对照组,差异有统计学意义(P＜0.05),其中得分最高的3个症状依次为抑郁/心境恶劣、情感淡漠、易激惹;其中幻觉、情感淡漠、异常行为等因子与认知障碍程度高度相关;异常行为与年龄、受教育程度均相关;同时对NPI各因子进行分析,获得了3个亚综合征,分别代表精神病性、情感异常和失控制行为. 结论 VaD患者普遍存在精神行为学症状,其症状的出现及严重程度与认知障碍、年龄、受教育程度有不同程度的相关性,各亚综合征中的子因子可能存在共同的病理生理基础.     

Improvement in behavioural symptoms in patients with moderate to severe Alzheimer's disease by memantine: a pooled data analysis

INTRODUCTION: Behavioural disturbances are a common and distressing aspect of Alzheimer's disease (AD). This pooled analysis evaluated the specific benefits of memantine on behavioural disturbances in patients with moderate to severe AD. METHODS: Data were pooled from six 24/28-week, randomised, placebo-controlled, double-blind studies. Of the 2,311 patients included in these studies, 1,826 patients with moderate to severe AD (MMSE <20) were included in this analysis, corresponding to the extended indication for memantine in Europe. In this subgroup, 959 patients received memantine 20 mg/day and 867 received placebo. Behavioural symptoms were rated using the Neuropsychiatric Inventory (NPI) total and single-item scores at weeks 12 and 24/28. RESULTS: At weeks 12 and 24/28, ITT analysis demonstrated that memantine treatment produced statistically significant benefits over placebo treatment in NPI total score (p=0.001 and p=0.008), and in NPI single items: delusions (p=0.007 week 12, p=0.001 week 24/28), hallucinations (p=0.037 week 12), agitation/aggression (p=0.001 week 12, p=0.001 week 24/28), and irritability/lability (p=0.005 week 24/28), LOCF population. Analysis of the patients without symptoms at baseline indicated reduced emergence of agitation/aggression (p=0.002), delusions (p=0.047), and disinhibition (p=0.011), at week 12, and of agitation/aggression (p=0.002), irritability/lability (p=0.004), and night-time behaviour (p=0.050) at week 24/28 in those receiving memantine. OC analyses yielded similar results. CONCLUSIONS: The data suggest that memantine is effective in treating and preventing the behavioural symptoms of moderate to severe AD. Specific persistent benefits were observed on the symptoms of delusions and agitation/aggression, which are known to be associated with rapid disease progression, increased caregiver burden, early institutionalisation, and increased costs of care.     

The use of the neuropsychiatric inventory in nursing home residents. Characterization and measurement.

The authors assessed the validity of the nursing home version of the Neuropsychiatric Inventory-Nursing Home Version (NPI-NH), comparing the responses of certified nurses' aides (CNAs) and licensed vocational nurses (LVNs) with research observations. Correlations were significant but moderate for all of the domains of the NPI-NH (delusions, hallucinations, agitation/aggression, depression, apathy, disinhibition, euphoria, irritability/lability, and aberrant motor disturbances) except anxiety and appetite disturbance. The LVNs' ratings showed consistently higher correlations with the researchers' behavioral observations than did the CNAs', but were moderate and generally better for residents with high levels of neuropsychiatric symptoms, thus, caution should be used with any untrained rater in the nursing home setting. The NPI-NH used by non-research staff can be useful in identifying residents with significant neuropsychiatric disturbances, but may be limited as an instrument for tracking behavioral changes.     

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.