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.     

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.     

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.     

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.     

Psychiatric morbidity in dementia patients in a neurology-based memory clinic

The behavioral and psychological symptoms of dementia (BPSD) often present major problems for patients and their caregivers. In the past, neurologists paid less attention to such symptoms than to the cognitive symptoms of dementia. This prospective study investigated the prevalence of psychiatric morbidity in a neurology-based memory clinic and the stress of caregivers. Our patients with dementia were found to have a high prevalence of BPSD. The most frequent were anxiety, apathy, and delusion; the most distressing to caregivers were agitation, anxiety, delusion, and sleep disturbance. Using Clinical Dementia Rating (CDR), we compared BPSD between patients with mild dementia and those with moderate dementia. Only hallucinations and agitation were different significantly. Moderate dementia patients experienced these symptoms more frequently. The high prevalence of these symptoms might be explained by the fact that the cognitive symptoms were neglected or no enough information were received by many family members of patients with dementia until their own life quality was interfered and then they began to seek medical help. These symptoms and their effect of caregiver distress can be effectively reduced by pharmacologic and nonpharmacoloic managements, caregiver-focused training and education. They can be better approached by assessing neuropsychiatric symptoms regularly, educating the general population better, and treating these patients earlier.     

Neuropsychiatric profiles in patients with Alzheimer's disease and vascular dementia

Background/Aims:

The aim of the following study is to compare the behavioral and psychological symptoms of dementia (BPSD) in patients of Alzheimer disease (AD) and vascular dementia (VaD).

Materials and Methods:

We used National Institute of Neurological and Communicative Disorders and Stroke-Alzheimer''s Disease and Related Disorders Association criteria for diagnosing AD and National Institute of Neurological Disorders and Stroke-Association International pour la Recherche et l’Enseignement en Neurosciences Criteria for diagnosing VaD. VaD cohort was further subcategorized into small vessel and large vessel disease. The severity of cognitive impairment and the BPSD were studied by means of the Clinical Dementia Rating Scale (CDR) and the Neuropsychiatric Inventory respectively.

Results:

We studied 50 AD and 50 VaD patients of whom 38 were small vessels and 12 were large vessels VaD. The severity of dementia was comparable in both groups. The agitation/aggression, depression/dysphoria, anxiety, apathy/indifference, irritability, aberrant motor behavior, appetite and eating behavior and night-time behaviors occurred significantly more frequently in patients with VaD than AD. We found a weak positive correlation between the CDR score and the number of neuropsychiatric symptoms per patient in both cohorts. Elation/euphoria, agitation/aggression was significantly more frequent in patients with large vessel in comparison to small vessel VaD.

Conclusions:

BPSD are common in both types of dementia and they are more severe in VaD than AD when the groups have similar levels of cognitive impairment.     

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.     

上海社区阿尔茨海默病行为和精神症状的发生率及影响因素

目的调查上海社区阿尔茨海默病（AD）患者行为和精神症状（BPSD）的发生率及分析可能的相关影响因素。方法对符合美国精神障碍诊断和统计手册第4版（DSM—IV）诊断标准的378例社区AD患者,进行一般资料调查,评定简易智力状态检查（MMSE）、临床痴呆评定表（CDR）及AD病理行为评分表（BEHAVE—AD）,分析BPSD症状发生率及有关的影响因素。结果BPSD的发生率为62．2％,其中以行为紊乱发生率最高（35．4％）,幻觉及焦虑恐惧最低（均为11．4％）,在接受BPSD治疗上仅为20％～25％。重度痴呆的幻觉及行为紊乱的发生率或因子分要高于轻、中度痴呆,而中度痴呆的情感障碍因子分最高。与AD患者BPSD有关的影响因素为病前生活事件、MMSE总分、年龄及CDR评分。结论社区AD患者的BPSD有较高的发生率,与BPSD发生的可能危险因素有生活事件、年龄及认知功能损害程度,需要引起足够的重视。     

Galantamine treatment of problematic behavior in Alzheimer disease: post-hoc analysis of pooled data from three large trials.

OBJECTIVE: The authors explored the effect of galantamine on behavioral symptoms in Alzheimer disease (AD). METHODS: Data were pooled from 2,033 subjects with mild-to-moderate AD who had participated in one of three randomized, double-blind, placebo-controlled trials of 3-, 5-, and 6-month durations. Subjects included in this post hoc analysis had received treatment with either placebo (N=686) or galantamine (N=1347) in total daily doses of 16 mg, 24 mg, or 32 mg. Behavioral symptoms were measured on the 10-item Neuropsychiatric Inventory (NPI). Four symptom clusters were defined a priori: 1) delusions, hallucinations; 2) agitation, depression, anxiety, apathy, irritability; 3) disinhibition, elation, aberrant motor behavior; 4) hallucinations, anxiety, apathy, aberrant motor behavior. RESULTS: At endpoint, mean changes from baseline in NPI scores were significantly different between galantamine-treated subjects and placebo-treated subjects, favoring galantamine for several measures: total NPI, individual domains of agitation/aggression, anxiety, disinhibition, and aberrant motor behavior, and Clusters 1, 3, and 4. The magnitude of the effect sizes was small. CONCLUSIONS: In this pooled sample of more than 2,000 subjects with mild-to-moderate AD, those who received galantamine therapy experienced modestly better, but statistically significant, outcomes in their behavioral symptoms than placebo-treated subjects. The cluster of hallucinations, anxiety, apathy and aberrant motor behaviors may represent a specific group of cholinergic-responsive behavioral symptoms.     

Role of serotonin transporter polymorphisms in the behavioural and psychological symptoms in probable Alzheimer disease patients

BACKGROUND/AIMS: Alzheimer disease (AD) patients commonly suffer from behavioural and psychological symptoms of dementia (BPSD). A genetic component to BPSD development in AD has been demonstrated. This is an investigation of whether the linked polymorphic region and variable number tandem repeat variants of the serotonin transporter (SERT) are associated with BPSD. METHODS: The longitudinal measures of BPSD of our large cohort of 367 AD patients were assessed by the Neuropsychiatric Inventory. Measures with good evidence of serotonergic involvement (delusions, hallucinations, depression, anxiety, agitation/aggression and irritability) were related to genotype and allele frequencies of the linked polymorphic region and variable number tandem repeat variants. RESULTS: Analysis revealed significant relationships between the linked polymorphic region variant long allele with irritability and the variable number tandem repeat 10-repeat allele with psychosis, but no associations were found with depression, anxiety or agitation/aggression. CONCLUSION: Our data and review of previous studies suggest SERT could play a minor role in development of psychosis and aggressive/irritable tendencies; however, further investigations are required in large, well-characterized cohorts.     

Quality of Life in relation to neuropsychiatric symptoms in Alzheimer's disease: 5‐year prospective ALSOVA cohort study

Objective

To examine the association between neuropsychiatric symptoms (NPS) with self‐ and caregiver‐rated Quality of Life (QoL) for patients with Alzheimer's disease (AD) during a 5‐year follow‐up.

Methods

The ALSOVA 5‐year follow‐up study included, at baseline, 236 patients with either very mild (Clinical Dementia Rating Scale (CDR) 0.5), or mild (CDR 1) AD, together with their caregivers from three Finnish hospital districts. QoL was evaluated using patient self‐reported, and caregiver‐rated, QoL in AD (QoL‐AD) scores. NPS were assessed using the Neuropsychiatric Inventory (NPI), and AD severity was evaluated using the CDR, with cognition tested by the mini‐mental state examination. The performance of daily activities was assessed using the Alzheimer's Disease Cooperative Study–Activities of Daily Living Inventory.

Results

Over the 5‐year follow‐up period, patient self‐reported QoL‐AD scores did not change significantly (p = 0.245), despite increases in their NPS. However, caregiver‐rated patient QoL‐AD scores declined significantly (p ≤ 0.001), as total NPI scores increased during follow‐up. No NPS at baseline, and only apathy at follow‐up, correlated significantly (p = 0.007) with patient self‐rated QoL‐AD scores. Caregiver‐rated patient QoL‐AD scores correlated significantly with most NPS, especially (p ≤ 0.001) apathy, agitation, anxiety, irritability, depression, and delusions at baseline, and delusions, hallucinations, apathy, appetite disturbances, and anxiety during follow‐up.

Conclusions

Patient rated QoL‐AD scores are an unreliable tool with which to evaluate the success of therapy for NPS. Instead, caregiver‐rated scores for patients correlated well with NPI scores, and health care professionals in the clinic should preferentially use these. Copyright © 2017 John Wiley & Sons, Ltd.     

A 2-year follow-up of behavioural and psychological symptoms in Alzheimer's disease

BACKGROUND: The aim was to examine the longitudinal occurrence and persistence of behavioural and psychological symptoms of dementia (BPSD) in Alzheimer's disease (AD). METHODS: Following 60 patients with mild to severe AD over a period of 2 years with annual evaluations, the prospective occurrence and persistence of BPSD in AD were determined by using the Behavioural Abnormalities in AD Rating scale (BEHAVE-AD). Clinical and demographic features of the AD patients were analysed for their association with course features of these symptoms. RESULTS: All of the 60 AD patients experienced BPSD at some point during the 2-year period, particularly agitation was present in every patient within this period. 2-year persistence of BPSD in AD was frequently observed in patients with agitation and with depressiveness, with less frequency in patients with anxiety and aggressiveness, but not in patients with delusions or hallucinations. 2-year persistent aggressiveness was associated with older age and more functional impairment. More functional impairment was also related to 2-year non-persistent hallucinations. CONCLUSIONS: Counselling AD patients and their families and tailoring therapeutic strategies should take into account the different modi of BPSD in AD occurring and persisting longitudinally and interacting with functional disturbances.     

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.     

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.     

Behavioral and psychological symptoms in Alzheimer's disease: frequency and relationship with duration and severity of the disease

The occurrence of behavioral and psychological symptoms of dementia (BPSD) is currently recognized as an important aspect of Alzheimer's disease (AD). We evaluated the frequency and severity of BPSD with the Neuropsychiatric Inventory across the various degrees and phases of the disease in 50 consecutive AD outpatients. Apathy, aberrant motor activity, dysphoria and anxiety were the symptoms most frequently reported by the caregivers, ranging in the whole study sample from 46 to 74%. A clear trend towards increasing frequency with the severity of disease was found for delusions, hallucinations and aberrant motor activity. A major effect of the duration of the disease was found in the probability of developing hallucinations and aberrant motor activity. Apart from hallucinations, all BPSD were present starting from a mild degree of dementia. A better understanding of the global spectrum of BPSD in AD is warranted in order to improve the allocation of health resources toward the treatment of dementia.     

Trazodone for the treatment of behavioral and psychological symptoms of dementia (BPSD) in Alzheimer's disease: a retrospective study focused on the aggression and negativism in caregiving situations]

Behavioral and psychological symptoms of dementia (BPSD) includes anxiety, depression, hallucination, delusion, aggression, irritability, agitation and wandering. BPSD often causes a deterioration of activity of daily living (ADL) and worsens caregiver burden. Trazodone, an atypical antidepressant, is used for the treatment of BPSD, but the effectiveness is controversial. In this study, we retrospectively analyzed the medical records of the 13 AD patients who were rated as having the aggression and negativism in caregiving situation and were treated by trazodone. The BPSD of the per-treatment stage of the patients was assessed with Neoropsychiatric Inventory(NPI). Improvement of BPSD after trazodone was observed in 9 patients, and the aggression and negativism in caregiving situations were improved in 6 patient. Trazodone may be effect for the treatment of a certain type of BPSD such as aggression and negativism in caregiving situations. Prospective studies of this issue are recommended in AD patient.     

Behavioural and psychological syndromes in Alzheimer's disease

OBJECTIVES: The origins of behavioural and psychological symptoms of dementia are still poorly understood. By focusing on piecemeal behaviours as opposed to more robust syndrome change valid biological correlates may be overlooked. Our understanding of BPSD via the identification of neuropsychiatric syndromes. METHODS: We recruited 435 subjects from old age psychiatry and elderly care memory outpatient clinics fulfilling the criteria for diagnosis of probable Alzheimer's disease. Behavioural and psychological symptoms were assessed using the Neuropsychiatric Inventory. Principal components factor analysis was carried out on the composite scores of the 12 symptom domains to identify behavioural syndromes (factors). Results were confirmed by performing three different rotations: Varimax, Equamax and Quartimax. RESULTS: Four factors were identified (which accounted for 57% of the variance): 'affect' factor-depression/dysphoria, anxiety, irritability/lability and agitation/aggression; 'physical behaviour' factor-apathy, aberrant motor behaviour, sleep disturbance and appetite/eating disturbance; 'psychosis' factor-delusions and hallucinations; 'hypomania' factor-disinhibition and elation/euphoria. These groups were unchanged when different methods of rotation were used. CONCLUSIONS: We report novel observations that agitation/aggression/irritability cluster within a depressive symptom factor and apathy is found within a physical behaviour factor.     

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.