Neuropsychiatric symptoms in mild dementia with lewy bodies and Alzheimer's disease

Background/Aims: To compare neuropsychiatric symptoms in patients with Alzheimer's disease (AD) and dementia with Lewy bodies(DLB). Methods: Neuropsychiatric symptoms and caregiver distress were assessed using the Neuropsychiatric Inventory (NPI) in mild DLB (n = 57) and AD (n = 126), and compared across the two groups using non-parametric tests. Results: The DLB patients had a higher NPI totalscore (median 24 vs. 11.5, p < 0.005), more numerous symptoms (median 5 vs. 4, p = 0.001) and more clinically significant symptoms (3 vs. 1, p = 0.001). They also had higher item hallucinations (6 vs. 2, p < 0.005) and apathy (7 vs. 5, p = 0.002) subscores. Caregivers scored higher on the NPI total caregiver distress scale (12.5 vs. 6, p = 0.003). Conclusions: In mild dementia, DLB patients have more neuropsychiatric symptoms and more associated caregiver distress compared with AD.     

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.     

Behavioral correlates of GABAergic disruption in Alzheimer's disease

BACKGROUND: Losses of gamma-aminobutyric acid (GABA) have been variably demonstrated in Alzheimer's disease (AD) and may be related to the presence of behavioral and psychological symptoms of dementia (BPSD) in AD. Our objective was to assess the relationship between plasma GABA (pGABA) levels and specific BPSD in patients with severe AD. METHODS: pGABA levels and BPSD were measured in 14 institutionalized AD patients (8M/6F, mean age +/- S.D. = 85.6 +/- 4.5 years) with severe cognitive impairment (Mini-mental State Examination score = 4.5 +/- 4.6) and prominent behavioral disturbances (Neuropsychiatric Inventory (NPI) score = 33.4 +/- 23.6). RESULTS: pGABA was positively correlated with depression and apathy scores on the NPI and negatively correlated with age. Apathy and age were independent predictors of pGABA levels. CONCLUSIONS: The final stages of AD are associated with GABAergic changes, which may contribute to depression and apathy in AD.     

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.     

The course of neuropsychiatric symptoms in dementia. Part I: findings from the two-year longitudinal Maasbed study

BACKGROUND: Although neuropsychiatric symptoms in dementia are common, there have been few large long-term prospective studies assessing the course of a broad range of neuropsychiatric symptoms in dementia. OBJECTIVES: To investigate the course of neuropsychiatric symptoms in patients with dementia, including data about prevalence, incidence and persistence. METHODS: One hundred and ninety-nine patients with dementia were assessed every six months for two-years, using the Neuropsychiatric Inventory (NPI) to evaluate neuropsychiatric symptoms. RESULTS: Nearly all patients (95%) developed one or more neuropsychiatric symptoms in the two-year study period. Mood disorders were the most common problem. The severity of depression decreased, whereas the severity of apathy and aberrant motor behaviour increased during follow-up. The cumulative incidence was highest for hyperactive behaviours and apathy. Overall behavioral problems were relatively persistent, but most symptoms were intermittent, with apathy and aberrant motor behaviour being persistent for longer consecutive periods. CONCLUSIONS: Neuropsychiatric symptoms in dementia are a common and major problem. Different symptoms have their own specific course, most of the time show a intermittent course, but behavioural problems overall are chronically present. The data have implications for developing treatment strategies.     

Neuropsychiatric symptoms in patients with multiple sclerosis

OBJECTIVE: To explore the range of psychiatric symptoms in patients with multiple sclerosis (MS) and their association with neurological disability. METHOD: Patients diagnosed with MS during 1998-2000 in Rogaland and Hordaland counties, western Norway, were included. Psychiatric symptoms were assessed by the Neuropsychiatric Inventory (NPI). Patients with systemic lupus erythematosus (SLE) served as controls. RESULTS: Eighty-six of 93 eligible MS patients were included, and 80% showed at least one psychiatric symptom. The most frequent symptoms were depression (59%), sleep disturbance (48%), irritability/emotional lability (42%), and apathy (31%). Depression was associated with higher disability score. MS patients showed significantly higher NPI irritability score (P = 0.002), appetite disturbance score (P < 0.001), and apathy score (P = 0.01) than SLE patients. CONCLUSION: Neuropsychiatric symptoms occur frequently in patients with MS. Irritability and apathy are independent of disability and chronic disease and represent unique disease manifestations.     

Validation of apathy evaluation scale and assessment of severity of apathy in Alzheimer's disease

Aim: Apathy is a well‐recognized symptom of Alzheimer's disease (AD). The aim of the present study was to validate the Taiwanese version of the Apathy Evaluation Scale, clinician version (AES‐C) and assess the severity of apathy in patients with AD. Methods: Comprehensive evaluations were conducted in a total of 144 AD patients. This study used a cross‐sectional comparative design. Data were collected from clinical interviews using the AES, the Mini‐Mental Status Examination (MMSE), the Neuropsychiatric Inventory (NPI), and the Clinical Dementia Rating Scale (CDR). Results: Internal consistency was indicated by Cronbach's alphas of 0.85; test–retest reliability was 0.89 over a period of 3 days. Criterion‐related validity was supported by the fact that AES‐C significantly correlated with the apathy scores of the NPI. Factor analysis indicated a three‐factor structure. Convergent validity was supported by a positive correlation between the AES‐C score and the anxiety score of the NPI. Discriminant validity was supported by the fact that the AES‐C scores did not correlate with the depression subscale of the NPI, and the correlation between the AES‐C score and the euphoria score of the NPI score was negative. Known‐group validity was supported by results showing that AD patients in a moderate stage of dementia (CDR = 2) had significantly higher scores on the AES‐C than patients with mild‐stage dementia (CDR = 1). Conclusion: The AES‐C is a reliable and valid instrument for measuring symptoms of apathy among AD patients in Taiwan.     

Neuropsychiatric symptoms and quality of life in Alzheimer disease.

OBJECTIVE: Authors examined the impact of neuropsychiatric symptoms in Alzheimer disease (AD) patients' and caregivers' quality of life (QOL) and assessed the relationship of caregiver distress to neuropsychiatric symptoms and caregiver QOL. METHODS: Sixty-two patients with probable or possible AD and their caregivers participated. Neuropsychiatric symptoms of patients were assessed with the Neuropsychiatric Inventory (NPI). QOL of both patients and caregivers was assessed using the QOL-Alzheimer's Disease (QOL-AD) scale. Each patient and caregiver completed patient QOL ratings; caregivers also completed caregiver QOL assessments. RESULTS: Caregiver QOL-AD was negatively correlated with agitation/aggression, anxiety, disinhibition, irritability/lability, and total NPI score. Patient QOL on both patient and caregiver ratings was negatively correlated with depression. Patient-reported QOL-AD ratings at different levels of cognitive functioning were not correlated with caregiver-reported ratings. The lack of relationship between patient and caregiver assessments of patient QOL was evident in both mildly and moderately affected patients. Caregiver QOL was negatively correlated with distress related to agitation/aggression, disinhibition, irritability/lability, and total NPI distress. CONCLUSION: Neuropsychiatric symptoms of AD patients adversely affect both patient and caregiver QOL. These results suggest that identifying and treating neuropsychiatric symptoms in AD may improve both patient and caregiver QOL.     

The persistence of neuropsychiatric symptoms in dementia: the Cache County Study

OBJECTIVE: To estimate the 18-month persistence of neuropsychiatric symptoms in dementia in a population-based sample, and to compare the severity of neuropsychiatric symptoms at baseline to the severity at 18-month follow-up. METHODS: A population-based sample of 329 residents of Cache County, Utah, diagnosed with dementia was rated on the Neuropsychiatric Inventory (NPI). Of the 204 participants with neuropsychiatric symptoms at baseline (defined as total NPI score >0), NPI data were obtained approximately 18 months later on 117 who were alive and available for follow-up. RESULTS: Eighty-one percent of those with neuropsychiatric symptoms at baseline (defined as total NPI score>0) continued to have at least one symptom at follow-up. Sixty-seven percent of participants with a clinically significant total NPI score (defined as > or = 4) at baseline continued to have a clinically significant total NPI score at follow-up. Among the ten neuropsychiatric domains assessed at baseline, delusions persisted in 65.5% of individuals, followed by depression (58.3%), and aberrant motor behavior (55.6%), while hallucinations and disinhibition persisted in only 25.0% and 11.1% respectively. In participants who were symptomatic at both baseline and follow-up, the mean severity scores at the two observation points were comparable in all ten neuropsychiatric domains. CONCLUSIONS: Neuropsychiatric symptoms in dementia overall were highly persistent. Among those in whom symptoms did persist, symptom severity a year and a half later appeared to be comparable.     

Neuropsychiatric symptoms in Alzheimer disease and cognitively impaired, nondemented elderly from a community-based sample in Brazil: prevalence and relationship with dementia severity.

OBJECTIVES: The objectives of this study were to describe the prevalence of neuropsychiatric symptoms of dementia in Alzheimer disease (AD) and cognitively impaired nondemented (CIND) subjects from a community-based Brazilian sample and to correlate these symptoms with severity of cognitive deficits. METHOD: A total of 1,563 randomly selected subjects were evaluated with the following screening tests: Mini-Mental Status Examination, Fuld Object Memory Evaluation, Informant Questionnaire on Cognitive Decline in the Elderly, and Activities of Daily Living-International Scale. Screen positives were submitted to a workup for dementia, physical and neurologic examination, cranial computed tomography or cerebral magnetic resonance imaging, the Cambridge Examination for Mental Disorders, Clinical Dementia Rating Scale (CDR), and the Neuropsychiatric Inventory (NPI). Diagnosis was made according to Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, criteria. RESULTS: Sixty patients with AD, 25 CIND, and 78 healthy elderly subjects were evaluated. Informants reported that 78.33% of patients with AD had one or more neuropsychiatric symptoms. Apathy (53.33%), depression (38.33%), sleep alterations (38.33%), and anxiety (25%) were the most prevalent disturbances in AD subjects. These disturbances were more prevalent in patients with AD than in the comparison group and CIND individuals. In the CIND group, the most frequent neuropsychiatric symptoms were anxiety and sleep alterations (both with 24%) followed by depression (16%). Total NPI scores were significantly different between AD and CIND groups, AD and comparison groups, and CIND and the comparison group. Apathy was the only neuropsychiatric symptom that was significantly different between the groups divided according to the CDR being more frequent in subjects with moderate to severe dementia. CONCLUSIONS: Neuropsychiatric symptoms seem to be as common in patients living in a developing country as they are in demented patients from the developed world. Indeed, the fact that some of our results are similar to other population-based studies may suggest that cultural factors play a minor role in the emergence of these symptoms, at least in a Latin American country like Brazil.     

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.     

Prevalence and correlates of neuropsychiatric symptoms in Parkinson's disease without dementia

A cross‐sectional study of the profile of psychiatric symptoms and their relationships to medications, executive performance, and excessive daytime somnolence (EDS) was conducted on 1351 consecutive Parkinson's disease patients without dementia (PD‐ND). Ratings were: neuropsychiatric inventory (NPI); hospital anxiety and depression scale (HADS); executive performance (semantic, phonemic, and alternating verbal fluencies); and the Epworth sleepiness scale (ESS). Eighty‐seven percent of the subjects reported at least one psychiatric symptom. The most common were depression (70%), anxiety (69%), apathy (48%), and irritability (47%). Fifty percent of the patients had HADS‐depression scores ranging from possible (8–10; 22%) to probable (≥11; 28%) depression. Executive impairment was found in 41% and EDS in 26% of subjects. All considered variables were significantly more common with longer duration and more severe disease. Only depression appeared to be influenced by type of medication, being less prevalent among patients treated with DAs. Five NPI clusters were identified among patients scoring ≥1 on the NPI (87.3%): patients exhibiting predominantly apathy (12.7%), psychosis (3%), depression (13%), anxiety (15.6%), and “low‐total NPI” (43.2%). Neuropsychiatric symptoms are common in nondemented PD patients suggesting that they are an integral part of PD from the beginning of the disease and appears more related to disease progression than to the type of antiparkinsonian medication. Apathy emerged as an independent construct in PD‐ND, indicating the need to address specific therapeutical approaches targeted toward this particular symptom. © 2008 Movement Disorder Society     

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.     

Depressive symptoms and regional cerebral blood flow in Alzheimer's disease

Depressive symptoms are common in patients with Alzheimer's disease (AD) and increase the caregiver burden, although the etiology and pathologic mechanism of depressive symptoms in AD patients remain unclear. In this study, we tried to clarify the cerebral blood flow (CBF) correlates of depressive symptoms in AD, excluding the effect of apathy and anxiety. Seventy-nine consecutive patients with AD were recruited from outpatient units of the Memory Clinic of Okayama University Hospital. The level of depressive symptoms was evaluated using the depression domain of the Neuropsychiatric Inventory (NPI). The patients underwent brain SPECT with 99mTc-ethylcysteinate dimer. After removing the effects of age, anxiety and apathy scores of NPI, and five subscales of Addenbrooke's Cognitive Examination-revised (ACE-R), correlation analysis of NPI depression scores showed a significant cluster of voxels in the left middle frontal gyrus (Brodmann area 9), similar to the areas in the simple correlation analysis. The dorsolateral prefrontal area is significantly involved in the pathogenesis of depressive symptoms in AD, and the area on the left side especially may be closely related to the depressive symptoms revealed by NPI.     

The Independent Contributions of Cognitive Impairment and Neuropsychiatric Symptoms to Everyday Function in Older Adults

The everyday functional capacities of older adults are determined by multiple factors. The primary goal of the present study was to evaluate whether apathy and depression have unique influences on degree of functional impairment, independent of the effects of specific cognitive impairments. Participants included 344 older adults (199 normal, 87 with MCI, 58 with dementia). The Everyday Cognition (ECog) scales were used to measure both global and domain-specific functional abilities. Neuropsychiatric symptoms of depression and apathy were measured by the Neuropsychiatric Inventory (NPI), and specific neuropsychological domains measured included episodic memory and executive functioning. Results indicated that worse memory and executive function, as well as greater depression and apathy, were all independent and additive determinants of poorer functional abilities. Apathy had a slightly more restricted effect than the other variables across the specific functional domains assessed. Secondary analysis suggested that neuropsychiatric symptoms may be more strongly associated with everyday function within cognitively normal and MCI groups, while cognitive impairment is more strongly associated with everyday function in dementia. Thus, a somewhat different set of factors may be associated with functional status across various clinical groups.     

Omega-3 supplementation in mild to moderate Alzheimer's disease: effects on neuropsychiatric symptoms

BACKGROUND: Epidemiological and animal studies have suggested that dietary fish or fish oil rich in omega-3 fatty acids (omega3), docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA), may have effects in psychiatric and behavioral symptoms in Alzheimer's disease (AD). An association with APOEomega4 carriers and neuropsychiatric symptoms in AD has also been suggested. OBJECTIVE: To determine effects of dietary omega3 supplementation to AD patients with mild to moderate disease on psychiatric and behavioral symptoms, daily functions and a possible relation to APOEgenotype. METHODS: Randomized, double-blind, placebo-controlled clinical trial where 204 AD patients (74+/-9 years) with acetylcholine esterase inhibitor treatment and a MMSE>15 points were randomized to daily intake of 1.7 g DHA and 0.6 g EPA (omega3 group) or placebo for 6 months. Then, all received the omega3 supplementation for 6 more months. Neuropsychiatric symptoms were measured with Neuropsychiatric Inventory (NPI) and Montgomery Asberg Depression Scale (MADRS). Caregivers burden and activities of daily living (Disability Assessment for Dementia, DAD) were also assessed. RESULTS: One hundred and seventy-four patients fulfilled the trial. 72% were APOEomega4 carriers. No significant overall treatment effects on neuropsychiatric symptoms, on activities of daily living or on caregiver's burden were found. However, significant positive treatment effects on the scores in the NPI agitation domain in APOEomega4 carriers (p=0.006) and in MADRS scores in non-APOEomega4 carriers (p=0.005) were found. CONCLUSIONS: Supplementation with omega3 in patients with mild to moderate AD did not result in marked effects on neuropsychiatric symptoms except for possible positive effects on depressive symptoms (assessed by MADRS) in non-APOEomega4 carriers and agitation symptoms (assessed by NPI) in APOEomega4 carriers. ClinicalTrials.gov identifier: NCT00211159     

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

OBJECTIVE: To explore the neuropsychiatric manifestations in patients with Alzheimer's disease (AD) and cortical and subcortical vascular dementia (VaD). METHODS: We investigated consecutive patients with dementia. All the participants received brain computed tomography. The diagnosis of dementia was confirmed by clinical criteria and the imaging findings. Only patients with probable AD, and subcortical and cortical VaD were included. The Mini Mental State Examination (MMSE) was used to evaluate global cognitive function, and the Neuropsychiatric Inventory (NPI) was used to assess neuropsychiatric symptoms. RESULTS: Of the 536 participants with dementia, 320 (59.7%) had AD, 161 (30%) had subcortical VaD, 35 (6.4%) had cortical VaD, and 16 (2.9%) had mixed cortical and subcortical VaD. Cortical VaD patients had the highest mean composite NPI scores in all domains and AD patients had the lowest composite scores in most domains. The mean composite scores of the apathy and sleep disturbance domains in patients with cortical VaD were significantly higher than those in the patients with AD after controlling for years of education and MMSE score (p < 0.01). CONCLUSIONS: There were few differences among the patients with AD, subcortical VaD and cortical VaD. The most consistent differences were the high sleep disturbance scores in those with cortical 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.     

Validity and reliability of the newly translated Hellenic Neuropsychiatric Inventory (H-NPI) applied to Greek outpatients with Alzheimer's disease: a study of disturbing behaviors among referrals to a memory clinic

CONTEXT: No rating scales of the neuropsychiatric symptoms of patients with dementia and Alzheimer's disease (AD) have previously been developed or translated. OBJECTIVES: To develop a Hellenic translation of the Neuropsychiatric Inventory (NPI), to evaluate it's reliability and validity, and to compare NPI results in Greek patients referred to a neuropsychiatry clinic for either of two reasons: disturbing behaviors evoking embarrassment and disturbing behaviors evoking fear in the caregiver. METHODS: The Hellenic translations of the NPI, Brief Psychiatric Rating Scale (BPRS), and Emotional Distress Scale (EDS) were compared in evaluating 29 consecutive referrals of patients with AD. RESULTS: The Hellenic NPI (H-NPI) demonstrated a high degree of internal consistency reliability, and of concurrent validity when compared to the BPRS or the EDS. Patients referred for behaviors evoking embarrassment presented with higher scores on NPI ratings of apathy. However, patients referred for behaviors evoking fear presented with higher scores on NPI ratings of aggression and irritability. CONCLUSIONS: These results indicate that the H-NPI is a reliable instrument, able to detect differences in clinically referred groups of AD patients.