Neuropsychiatric Inventory Scores Research Articles

Effects of anosognosia and neuropsychiatric symptoms on the quality of life of patients with Alzheimer's disease: a 24-month follow-up study.

Neuropsychiatric symptoms and anosognosia are known to influence the perceived quality of life of patients (QoL-p) with Alzheimer's disease (AD). This study analysed their impact on patient and caregiver ratings of QoL-p and how these ratings changed in relation to the severity of dementia. A baseline sample of 221 patients and caregivers was followed up over 24 months. Instruments: Neuropsychiatric Inventory (NPI), Anosognosia Questionnaire-Dementia (AQ-D), Quality of life-Alzheimer's Disease (QoL-AD) and the Global Deterioration Scale (GDS). Longitudinal data were analysed using generalized linear models. In the multivariate analysis, greater anosognosia was always associated with higher ratings of QoL-p among patients, especially at 24 months (p < 0.001), and with more negative ratings among caregivers, especially at baseline (p < 0.001). A higher total NPI score was associated with a more negative rating of QoL-p among caregivers (p < 0.001), and it also had a smaller negative effect on patients' self-ratings (p = 0.001). The neuropsychiatric symptoms (NPI) associated with a more negative view of QoL-p were depression, for patients' self-ratings, and apathy and agitation for caregiver ratings. The discrepancy between patient and caregiver ratings increased in line with the severity of dementia. Neuropsychiatric symptoms had a similarly negative effect on the QoL-p ratings of both patients and caregivers, whereas the effect of anosognosia differed according to the rater (positive for patients, negative for caregivers).

Change patterns, influencing factors and predictors of quality of life in patients with Alzheimer's disease

To explore the change patterns, influencing factors and predictors of quality of life for 4 years in patients with Alzheimer's disease (AD). A total of 96 mild-moderate AD patients on combined therapies of medicine and recuperation were enrolled. Their clinical symptoms were graded by mini-mental state examination (MMSE), activity of daily living (ADL), global deterioration scale (GDS), neuropsychiatric inventory (NPI), Hamilton depression scale (HRSD), Hamilton anxiety scale (HAMA) and Pittsburgh sleep quality index (PQSI). And their qualities of life were evaluated by Quality of Life-Alzheimer's Disease (QOL-AD) at baseline and at the end of 1, 2, 3, 4 year. (1) During a 4-year follow-up, the scores of QOL-AD, MMSE, ADL, GDS, NPI, HRSD, HAMA and PQSI decreased markedly compared with baseline [(17.5±1.9), (12±3), (45±9), (5.2±0.8), (31±11), (20±6), (14±6), (14±4) vs (30.5±4.6), (21±4), (34±10), (3.3±0.9), (22±9), (18±6), (11±4), (12±4) respectively, t=25.31, 15.42, -7.16, -14.83, -5.56, -2.94, -4.45, -5.60, all P<0.01]. With the deterioration of AD, their qualities of life decreased significantly. (2) Spearman's correlation analysis showed that the scores of 4-year QOL-AD were correlated with the 4-year score changes of MMSE, ADL, GDS (r=0.344, 0.368, 0.213; P=0.002, 0.001, 0.047). (3) Multiple Logistic regression model showed that the baseline scores of NPI and HRSD were strong predictors of loss of quality of life (OR=1.697, 1.269; P=0.000, 0.006). And the area under the curve of receiver operating characteristic (ROC) of NPI and HRSD were 0.918 (95% CI: 0.844-0.991) and 0.878 (95% CI: 0.804-0.953) respectively. With the deterioration of AD, the quality of life decreases significantly and has correlations with the score changes of MMSE, ADL and GDS. High scores of NPI and HRSD are the important predictors for a loss of quality of life in AD patients. Early detection and timely interventions are necessary.

A neurophysiological profile in Parkinson’s disease with mild cognitive impairment and dementia in China

Mild cognitive impairment (MCI) and dementia (D) are frequent features of Parkinson’s disease (PD) but widely disparate criteria have been used. Our understanding of the prevalence and cognitive profile of Chinese PD patients remains limited. In order to determine the frequency and pattern of cognitive dysfunction and identify risk factors for cognitive dysfunction in the Chinese Han PD population we performed a cross-sectional study in a cohort of 330 PD patients and 163 healthy controls. Five cognitive domains (executive function, attention, praxis and visuospatial function, memory, and language) and mood/behavior were evaluated. According to the Movement Disorder Society Task Force consensus criteria, up to 29.1% of PD patients were classified as PD-MCI and 32.1% as PD-D. Impairments occur in a range of cognitive domains with dysexecutive profile predominating. Healthy controls also outperformed cognitively preserved PD patients in tasks of executive function and attention. Logistic regression indicated that PD-MCI may be predicted by lower educational level and apathy. Additionally, later disease onset, longer disease duration, more severe motor symptoms and higher neuropsychiatric inventory score were associated with a faster transition from PD-MCI to PD-D. These findings suggest that all PD patients should undergo routine cognitive screening. For high-risk patients early recognition and therapeutic intervention is imperative.

Changing practice in dementia care in the community: developing and testing evidence-based interventions, from timely diagnosis to end of life (EVIDEM)

BackgroundThe needs of people with dementia and their carers are inadequately addressed at all key points in the illness trajectory, from diagnosis through to end-of-life care. The EVIDEM (Evidence-based Interventions in Dementia) research and development programme (2007–12) was designed to help change this situation within real-life settings.ObjectivesThe EVIDEM projects were (1) evaluation of an educational package designed to enhance general practitioners’ (GPs’) diagnostic and management skills; (2) evaluation of exercise as therapy for behavioural and psychological symptoms of dementia (BPSD); (3) development of a toolkit for managing incontinence in people with dementia living at home; (4) development of a toolkit for palliative care for people with dementia; and (5) development of practice guidance on the use of the Mental Capacity Act (MCA) 2005.DesignMixed quantitative and qualitative methods from case studies to large database analyses, including longitudinal surveys, randomised controlled trials and research register development, with patient and public involvement built into all projects.SettingGeneral practices, community services, third-sector organisations and care homes in the area of the North Thames Dementia and Neurodegenerative Diseases Research Network local research network.ParticipantsPeople with dementia, their family and professional carers, GPs and community mental health team members, staff in local authority social services and third-sector bodies, and care home staff.Main outcome measuresDementia management reviews and case identification in general practice; changes in behavioural and psychological symptoms measured with the Neuropsychiatric Inventory (NPI); extent and impact of incontinence in community-dwelling people with dementia; mapping of pathways to death of people with dementia in care homes, and testing of a model of collaborative working between primary care and care homes; and understandings of the MCA 2005 among practitioners working with people with dementia.ResultsAn educational intervention in general practice did not alter management or case identification. Exercise as a therapy for BPSD did not reduce NPI scores significantly, but had a significant positive effect on carer burden. Incontinence is twice as common in community-dwelling people with dementia than their peers, and is a hidden taboo within a stigma. Distinct trajectories of dying were identified (anticipated, unexpected and uncertain), and collaboration between NHS primary care and care homes was improved, with cost savings. The MCA 2005 legislation provided a useful working framework for practitioners working with people with dementia.ConclusionsA tailored educational intervention for general practice does not change practice, even when incentives, policy pressure and consumer demand create a favourable environment for change; exercise has potential as a therapy for BPSD and deserves further investigation; incontinence is a common but unrecognised problem for people with dementia in the community; changes in relationships between care homes and general practice can be achieved, with benefits for people with dementia at the end of life and for the UK NHS; application of the MCA 2005 will continue to improve but educational reinforcements will help this. Increased research capacity in dementia in the community was achieved. This study suggests that further work is required to enhance clinical practice around dementia in general practice; investigate the apparent beneficial effect of physical activity on BPSD and carer well-being; develop case-finding methods for incontinence in people with dementia; optimise working relationships between NHS staff and care homes; and reinforce practitioner understanding of the MCA 2005.Trial registrationEVIDEM: ED-NCT00866099; EVIDEM: E-ISRCTN01423159.FundingThis project was funded by the Programme Grants for Applied Research programme of the National Institute for Health Research.

Association between caregiver depression and individual behavioral and psychological symptoms of dementia in Taiwanese patients.

The aim of this study was to investigate caregiver depression associated with neuropsychiatric symptoms in Taiwanese people. A cross-sectional design was used in this study. Two hundred seventy-six pairs of patients with dementia and their caregivers who visited the memory clinic of a general hospital from July 2001 to October 2008 were recruited. Caregiver depression was evaluated with the Center for Epidemiologic Studies Depression Scale (CES-D); the behavioral and psychological symptoms of dementia were evaluated using the Neuropsychiatric Inventory. Demographic data of the patients and caregivers, including cognitive functions and clinical dementia ratings, were collected. In addition to descriptive statistics, we examined the relationship between each parameter and caregiver depression using Pearson correlation, independent t-test, or analysis of variance. The results showed a statistically significant positive correlation between the total Neuropsychiatric Inventory score and CES-D score (r = 0.345, P < 0.001) in the bivariate analyses. For individual behavioral and psychological symptoms of dementia, agitation/aggression, anxiety, nighttime behavior disturbances, irritability/lability, and hallucinations were the five leading symptoms significantly associated with caregiver depression (CES-D). Carefully managing these symptoms is likely to reduce depression in dementia caregivers.

Anosognosia in People with Cognitive Impairment: Association with Cognitive Deficits and Behavioral Disturbances

Aims: To investigate, in a group of subjects at an early stage of cognitive impairment, the relationship between anosognosia and both cognitive and behavioral symptoms by exploring the various domains of insight. Methods: One hundred and eight subjects affected by cognitive impairment were consecutively enrolled. The level of awareness was evaluated by means of the Clinical Insight Rating Scale (CIRS). Psychiatric symptoms were evaluated using the Italian version of the Neuropsychiatric Inventory (NPI), whereas memory (memory index, MI) and executive (executive index, EI) functions were explored using a battery of neuropsychological tests and qualified by means of a single composite cognitive index score for each function. Results: A significant positive correlation between the total NPI score and global anosognosia score was found. Furthermore, both the MI and EI scores were lower in subjects with anosognosia than in those without anosognosia (p < 0.001 and p < 0.007, respectively). When the single domains of the CIRS were considered, anosognosia of reason of visit correlated with the EI score (r = -0.327, p = 0.01) and night-time behavioral disturbances (r = 0.225; p = 0.021); anosognosia of cognitive deficit correlated with depression (r = -0.193; p = 0.049) and the MI score (r = -0.201; p = 0.040); anosognosia of functional deficit correlated with the MI score (r = -0.257; p = 0.008), delusions (r = 0.232; p = 0.015) and aberrant motor behavior (r = 0.289; p = 0.003); anosognosia of disease progression correlated with the MI score (r = -0.236; p = 0.015), agitation (r = 0.247; p = 0.011), aberrant motor behavior (r = 0.351; p = 0.001) and night-time behavioral disturbances (r = 0.216; p = 0.027). Conclusions: Our study suggests that, in the early stage of cognitive impairment, anosognosia is associated with both cognitive deficits and behavioral disorders according to the specific functional anatomy of the symptoms.

Prediction of general hospital admission in people with dementia: cohort study.

People with dementia are extremely vulnerable in hospital and unscheduled admissions should be avoided if possible. To identify any predictors of general hospital admission in people with dementia in a well-characterised national prospective cohort study. A cohort of 730 persons with dementia was drawn from the Scottish Dementia Research Interest Register (47.8% female; mean age 76.3 years, s.d. = 8.2, range 50-94), with a mean follow-up period of 1.2 years. In the age- and gender-adjusted multivariable model (n = 681; 251 admitted), Neuropsychiatric Inventory score (hazard ratio per s.d. disadvantage 1.21, 95% CI 1.08-1.36) was identified as an independent predictor of admission to hospital. Neuropsychiatric symptoms in dementia, measured using the Neuropsychiatric Inventory, predict non-psychiatric hospital admission of people with dementia. Further studies are merited to test whether interventions to reduce such symptoms might reduce unscheduled admissions to acute hospitals.

A new simple score (ABS) for assessing behavioral and psychological symptoms of dementia

In addition to cognitive impairment, behavioral and psychological symptoms of dementia (BPSD) are another important aspect of most dementia patients. This study was designed for a new simple assessment of BPSD. We first employed a clinical survey for the local community with sending an inquiry letter to all members (n=129) of dementia caregiver society, and then attempted to create a new BPSD score for dementia with 10 BPSD items. This new simple BPSD score was compared to a standard-detailed BPSD score neuropsychiatric inventory (NPI) for a possible correlation (n=792) and a time to complete (n=136). Inter-rater reliability was examined comparing scores between main and second caregivers (n=70) for AD. Based on the clinical survey for local caregivers, a new BPSD score for dementia (ABS, Abe's BPSD score) was newly created, in which each BPSD item was allotted by an already-weighted score (maximum 1–9) based on the frequency and severity, and was finalized with taking temporal occurrences into account. ABS was filled by the main caregiver with a full score of 44, was well correlated with NPI (r=0.716, **p<0.01) in 792 AD patients (age 78.6±7.0years, MMSE 19.0±5.9), and took a shorter time as only 56.8±38.8s (**p<0.01) than NPI score (132.7±94.0s) with 136 AD patients. A high inter-rater reliability was obtained (r=0.964, **p<0.01) with a little smaller score (0.877 time) of ABS in secondary than the main caregivers. ABS provides a new simple and quick test for BPSD assessment, with a good correlation to NPI but a shorter time, and with a high inter-rater reliability. Thus ABS is useful for evaluating BPSD for mild to moderate dementia patients.

Neuropsychiatric symptoms in patients with vascular dementia in mainland China.

BackgroundNeuropsychiatric deficits can induce marked disability in patients with dementia and increase caregiver distress. Several studies have found that neuropsychiatric symptoms are common both in patients with Alzheimer’s disease (AD) and patients with vascular dementia (VaD). However, there are few studies of the neuropsychiatric disturbances in large clinical samples of patients with mixed (cortical - subcortical) VaD from mainland China. This study aimed to investigate the neuropsychiatric symptoms in VaD patients in mainland China.MethodsEighty patients with mixed VaD for over 6 months duration, and their caregivers (VaD group), were recruited for interview in Zhongnan Hospital of Wuhan University, from June 2010 to June 2012. Eighty age- and sex-matched normal volunteers (control group) were interviewed at the same time. The Mini Mental State Examination (MMSE) and the Neuropsychiatric Inventory (NPI) were administered to the VaD patients, their caregivers, and normal volunteers. Group differences were analyzed using the unpaired t-test.ResultsThe total mean scores of the NPI in the VaD group were higher than in the control group (P < 0.01). The subscale scores of NPI, including delusions, hallucinations, depression, apathy, irritability, agitation, aberrant motor behavior, and change in appetite were significantly higher in the VaD group than in the control group (P < 0.05–0.01). Compared with the mild VaD subgroup, the NPI subscale scores of apathy, irritability and total scores were significantly higher in the moderate VaD subgroup (P < 0.05–0.01); the NPI subscale scores of anxiety, apathy, irritability, and total scores were significantly higher in the severe VaD subgroup (P < 0.01). Compared with the moderate VaD subgroup, the NPI subscale scores of anxiety and apathy were significantly higher in the severe VaD subgroup (P < 0.05–0.01).ConclusionsNeuropsychiatric symptoms, such as hallucination, anxiety, apathy, irritability and aberrant action behavior, are common in patients with mixed VaD from mainland China; anxiety and apathy were more pronounced in the subgroup of severe VaD patients.

A Comparison of Lamotrigine or Sodium Valproate on the Efficacy in Alzheimer’s disease with Behavioral and Psychological Symptoms of Dementia: A Retrospective Open-Label Study Running Title: Efficacy of Anticonvulsants for BPSD

Aim: We compared the clinical efficacy and subsequent changes in dosages of concomitantly used psychotropic drugs with lamotrigine and sodium valproate therapy in Alzheimer’s disease (AD) with Behavioral and Psychological Symptoms on Dementia (BPSD). Methods: This study was a 16-week, retrospective, open-label study. The 45 subjects were inpatients. The outcome measures assessed were BPSD and cognitive function. BPSD was assessed using the neuropsychiatric inventory (NPI) and cognitive function was assessed using the mini-mental examination (MMSE). The changes in the dosages of concomitant psychotropic drugs were also assessed. Results: Although the mean changes from baseline NPI scores and the two NPI subscales (agitation and irritability) decreased both in the lamotrigine therapy group and in the sodium valproate therapy group, no significant difference was found between the two groups. The mean decrease in diazepam-equivalent dose from baseline was significantly greater in the lamotrigine therapy group than that in the sodium valproate therapy group (p < 0.05). Furthermore, in the sodium valproate therapy group, the occurrence rates of somnolence, body tilt, and dizziness were all 30%. Conclusions: The results of this study suggested that while the administration of lamotrigine or sodium valproate might be effective in patients with severe AD with BPSD, special attention is required when using sodium valproate on a daily basis.

Neuropsychiatric symptoms in Parkinson's disease dementia are associated with increased caregiver burden.

ObjectiveNeuropsychiatric symptoms are common in Parkinson’s disease dementia (PDD). Frequent and severe neuropsychiatric symptoms create high levels of distress for patients and caregivers, decreasing their quality of life. The aim of this study was to investigate neuropsychiatric symptoms that may contribute to increased caregiver burden in PDD patients.MethodsForty-eight PDD patients were assessed using the 12-item Neuropsychiatric Inventory (NPI) to determine the frequency and severity of mental and behavioral problems. The Burden Interview and Caregiver Burden Inventory were used to evaluate caregiver burden.ResultsAll but one patient showed one or more neuropsychiatric symptoms. The three most frequent neuropsychiatric symptoms were apathy (70.8%) and anxiety (70.8%), followed by depression (68.7%). More severe neuropsychiatric symptoms were significantly correlated with increased caregiver burden. The domains of delusion, hallucination, agitation and aggression, anxiety, irritability and lability, and aberrant motor behavior were associated with caregiver stress. After controlling for age and other potential confounding variables, total NPI score was significantly associated with caregiver burden.ConclusionsThe results of this study confirm that neuropsychiatric symptoms are frequent and severe in patients with PDD and are associated with increased caregiver distress. A detailed evaluation and management of neuropsychiatric symptoms in PDD patients appears necessary to improve patient quality of life and reduce caregiver burden.

Efficacy and safety of galantamine treatment for patients with Alzheimer's disease: a meta-analysis of randomized controlled trials.

Cholinesterase inhibitors treatment is considered as a common therapeutic approach for Alzheimer's disease (AD) by numerous reported studies, but the role of currently available drugs for AD is still controversial. Our study aimed to evaluate the efficacy and safety of galantamine for the treatment of AD, and provide the basis and reference for clinical rational drug use. Randomized controlled trials (RCTs) of galantamine for AD published up to April 30, 2014 were searched. A random or fixed-effect model was used to analyze outcomes which were expressed as risk ratios (RRs) or mean difference (MD) with a 95 % confidence interval (CI). Heterogeneity was assessed by Q test and I(2) statistic. The outcome measurements were as follows: the changes of Alzheimer's Disease Assessment Scale-cognitive subscale (ADAS-cog), Mini-Mental State Examination (MMSE), Activities of Daily Living (ADL), Neuropsychiatric Inventory (NPI), Clinicians' Interview-Based Impression of Change with Caregiver's Input (CIBIC+), adverse effects and dropouts. Eleven articles with 4,074 participants were included. Administration of galantamine for 8-28 weeks (16-40 mg daily) led to significant improvements in ADAS-cog score [P < 0.00001, MD = -2.95, 95 % CI (-3.32, -2.57)], MMSE score [P = 0.003, MD = 2.50, 95 % CI (0.86, 4.15)], NPI score [P = 0.001, MD = -1.58, 95 % CI (-2.54, -0.62)], and CIBIC+ scale [P < 0.00001, RR = 1.26, 95 % CI (1.15, 1.39)], but not in ADL score [P = 0.43, MD = 0.71, 95 % CI (-1.07, 2.48)]. More adverse events and dropouts occurred in the galantamine group than that in the placebo group, the differences were statistically significant (all P < 0.05). Galantamine could significantly improve cognitive, behavioral, and global performances in patients with AD. In addition, we need to use it with caution in the clinical treatment.

Vascular Risk as a Predictor of Cognitive Decline in a Cohort of Elderly Patients with Mild to Moderate Dementia

Background/Aims: The purpose of our study was to evaluate vascular risk factors and other clinical variables as predictors of cognitive and functional decline in elderly patients with mild to moderate dementia. Methods: The clinical characteristics of 82 elderly patients (mean age 79.0 ± 5.9 years; 67.1% females) with mild to moderate dementia were obtained at baseline, including years of education, Framingham Coronary Heart Disease Risk score, Hachinski Ischemic Score (HIS), Clinical Dementia Rating (CDR), Mini-Mental State Examination (MMSE) score, Functional Activities Questionnaire (FAQ) score, Burden Interview Scale score, and Neuropsychiatric Inventory (NPI) score. Changes in MMSE and FAQ scores over time were assessed annually. The association between baseline clinical variables and cognitive and functional decline was investigated during 3 years of follow-up through the use of generalized linear mixed effects models. Results: A trend was found towards steeper cognitive decline in patients with less vascular burden according to the HIS (β = 0.056, p = 0.09), better cognitive performance according to the CDR score (β = 0.313, p = 0.06) and worse caregiver burden according to the Burden Interview Scale score (β = -0.012, p = 0.07) at baseline. Conclusion: Further studies with larger samples are necessary to confirm and expand our findings.

Serum homocysteine levels are correlated with behavioral and psychological symptoms of Alzheimer's disease.

PurposeHomocysteine has been associated with cognitive impairment and various psychiatric symptoms. This study was designed to clarify whether a relationship exists between the serum levels of homocysteine and the behavioral and psychological symptoms of dementia.MethodsPatients with Alzheimer’s disease (n=77) and control subjects (n=37) were included in this study. History taking, physical examination, and cognitive assessment were carried out as part of the investigation for the diagnosis of Alzheimer’s disease based on the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition. The Mini-Mental State Examination, Global Deterioration Scale, Clinical Dementia Rating, and the Korean version of the Neuropsychiatric Inventory were applied to all patients. The patients’ serum homocysteine, folate, and vitamin B12 levels were measured.ResultsPatients with Alzheimer’s disease had statistically significantly lower Mini-Mental State Examination scores and higher serum homocysteine levels compared to the control subjects. Mean serum folate and vitamin B12 concentration were significantly lower in patients with Alzheimer’s disease compared to control subjects. A statistically significant positive correlation was found between the serum homocysteine levels and the Neuropsychiatric Inventory subdomains, including delusion, agitation/aggression, depression/dysphoria, elation/euphoria, apathy/indifference, and disinhibition. No statistically significant correlation was found between the serum homocysteine concentration and the Mini-Mental State Examination, Global Deterioration Scale, or Clinical Dementia Rating.ConclusionAssociations between the serum homocysteine levels and behavioral and psychological symptoms of dementia were observed, raising the possibility of an etiological role. However, the correlations between the folate or vitamin B12 levels and the Neuropsychiatric Inventory scores were not significant. The pathophysiological mechanisms underlying these findings remain to be elucidated. This was a cross-sectional study and the findings should be confirmed by repetitive, prospective longitudinal studies in a larger group of patients with neurodegenerative disorders.

Neuropsychiatric symptoms in people screened positive for dementia in primary care.

Neuropsychiatric symptoms are major determinants for caregiver distress and institutionalization in dementia. Little is known about the prevalence of neuropsychiatric symptoms and their association with use of medication, caregiver distress, and resource utilization in primary care. We assessed frequency of neuropsychiatric symptoms in a sample retrieved from a primary care intervention study. Patients were screened for dementia by their primary care physicians. A study nurse assessed neuropsychiatric symptoms in 176 patients using the neuropsychiatric inventory (NPI) through face-to-face interviews by proxy during home visits. In addition, data on global cognition (MMSE), quality of life (QoL-AD), resource utilization in dementia (RUD), caregiver distress (BIS), and use of psychotropic medication in patients were obtained. We used linear mixed effect models taking into account the clustering of patients within general physician practices. Clinically relevant neuropsychiatric symptoms (NPI score ≥ 4) occurred in about 53% of the patients. Higher NPI scores were significantly associated with more severe cognitive impairment, higher caregiver distress, and higher utilization of caregiver resources by patients but not with a formal diagnosis of dementia from the primary care physician. Use of antipsychotics was associated with higher NPI scores, particularly in non-psychotic domains. Neuropsychiatric symptoms in a primary care cohort screened positive for dementia were associated with resource utilization and distress of caregivers. In contrast to guideline recommendations, the use of antipsychotics was associated with non-psychotic domains of behavioral symptoms. These findings underscore the relevance of neuropsychiatric symptoms for the design of future interventions in primary care.

Neuropsychiatric symptoms in dementia-a role for neuroinflammation?

Dementia is characterized by a progressive cognitive decline and neuropsychiatric symptoms (NPSD) such as agitation, apathy and sleeping problems. There is some evidence of activation of inflammatory pathways in the brain in dementia, but little research has been performed regarding the role of neuroinflammation in NPSD, which might represent a potential novel target for treatment. The aim of this study was to examine the possible association between NPSD and cerebrospinal fluid (CSF) levels of the cytokines IL-6, TNF-α and IL-10, and the cytokine receptor sIL-1RII, in patients with dementia and NPSD. Ninety-four patients (mean age 79±8; 67% female) with a score on the neuropsychiatric inventory (NPI) ≥10 points, were included. Clinical assessment included administration of NPI, the mini-mental state examination (MMSE) and the Cohen-Mansfield agitation inventory (CMAI). The cytokine levels in CSF samples were analysed by enzyme-linked immunosorbent assay. Correlations were statistically examined using Spearman's rank correlation coefficient (r), and simple- and multiple-linear regression. The anti-inflammatory cytokine IL-10 showed reverse correlations with total NPI score (NPI-total=-0.001, t(90)= 8.50, p=0.004) and NPI sub-items agitation (agitation=-0.007, t(90)=7.02, p=0.009) and night-time behaviour (night time behaviour=-0.006, t(90)=6.34, p=0.01). There was a trend towards reverse correlation between IL-10 and depression (depression=-0.004, t(90)=2.96, p=0.09). Also, the soluble cytokine receptor sIL-1RII showed a trend towards correlation with apathy (apathy=0.82, t(82)=3.62, p=0.06). The levels of IL-6 showed no significant correlations with NPSD. Levels of TNF-α were non-detectable. In Alzheimer's disease (AD) subjects (n=33), IL-6 showed reverse correlation with anxiety (r=-0.35, p=0.049). In mixed AD subjects (n=26), IL-10 showed reverse correlations with the total NPI score (r=-0.46, p=0.02) and depression (r=-0.45, p=0.02). The findings indicate a relationship between neuroinflammation and neuropsychiatric symptoms in AD in which anti-inflammatory signalling by IL-10 is beneficial from a mental health perspective.

A systematic review of the clinical effectiveness and cost-effectiveness of sensory, psychological and behavioural interventions for managing agitation in older adults with dementia.

Agitation is common, persistent and distressing in dementia and is linked with care breakdown. Psychotropic medication is often ineffective or harmful, but the evidence regarding non-pharmacological interventions is unclear. We systematically reviewed and synthesised the evidence for clinical effectiveness and cost-effectiveness of non-pharmacological interventions for reducing agitation in dementia, considering dementia severity, the setting, the person with whom the intervention is implemented, whether the effects are immediate or longer term, and cost-effectiveness. We searched twice using relevant search terms (9 August 2011 and 12 June 2012) in Web of Knowledge (incorporating MEDLINE); EMBASE; British Nursing Index; the Health Technology Assessment programme database; PsycINFO; NHS Evidence; System for Information on Grey Literature; The Stationery Office Official Documents website; The Stationery National Technical Information Service; Cumulative Index to Nursing and Allied Health Literature; and The Cochrane Library. We also searched Cochrane reviews of interventions for behaviour in dementia, included papers' references, and contacted authors about 'missed' studies. We included quantitative studies, evaluating non-pharmacological interventions for agitation in dementia, in all settings. We rated quality, prioritising higher-quality studies. We separated results by intervention type and agitation level. As we were unable to meta-analyse results except for light therapy, we present a qualitative evidence synthesis. In addition, we calculated standardised effect sizes (SESs) with available data, to compare heterogeneous interventions. In the health economic analysis, we reviewed economic studies, calculated the cost of effective interventions from the effectiveness review, calculated the incremental cost per unit improvement in agitation, used data from a cohort study to evaluate the relationship between health and social care costs and health-related quality of life (DEMQOL-Proxy-U scores) and developed a new cost-effectiveness model. We included 160 out of 1916 papers screened. Supervised person-centred care, communication skills (SES = -1.8 to -0.3) or modified dementia care mapping (DCM) with implementing plans (SES = -1.4 to -0.6) were all efficacious at reducing clinically significant agitation in care home residents, both immediately and up to 6 months afterwards. In care home residents, during interventions but not at follow-up, activities (SES = -0.8 to -0.6) and music therapy (SES = -0.8 to -0.5) by protocol reduced mean levels of agitation; sensory intervention (SES = -1.3 to -0.6) reduced mean and clinically significant symptoms. Advantages were not demonstrated with 'therapeutic touch' or individualised activity. Aromatherapy and light therapy did not show clinical effectiveness. Training family carers in behavioural or cognitive interventions did not decrease severe agitation. The few studies reporting activities of daily living or quality-of-life outcomes found no improvement, even when agitation had improved. We identified two health economic studies. Costs of interventions which significantly impacted on agitation were activities, £80-696; music therapy, £13-27; sensory interventions, £3-527; and training paid caregivers in person-centred care or communication skills with or without behavioural management training and DCM, £31-339. Among the 11 interventions that were evaluated using the Cohen-Mansfield Agitation Inventory (CMAI), the incremental cost per unit reduction in CMAI score ranged from £162 to £3480 for activities, £4 for music therapy, £24 to £143 for sensory interventions, and £6 to £62 for training paid caregivers in person-centred care or communication skills with or without behavioural management training and DCM. Health and social care costs ranged from around £7000 over 3 months in people without clinically significant agitation symptoms to around £15,000 at the most severe agitation levels. There is some evidence that DEMQOL-Proxy-U scores decline with Neuropsychiatric Inventory agitation scores. A multicomponent intervention in participants with mild to moderate dementia had a positive monetary net benefit and a 82.2% probability of being cost-effective at a maximum willingness to pay for a quality-adjusted life-year of £20,000 and a 83.18% probability at a value of £30,000. Although there were some high-quality studies, there were only 33 reasonably sized (> 45 participants) randomised controlled trials, and lack of evidence means that we cannot comment on many interventions' effectiveness. There were no hospital studies and few studies in people's homes. More health economic data are needed. Person-centred care, communication skills and DCM (all with supervision), sensory therapy activities, and structured music therapies reduce agitation in care-home dementia residents. Future interventions should change care home culture through staff training and permanently implement evidence-based treatments and evaluate health economics. There is a need for further work on interventions for agitation in people with dementia living in their own homes. The study was registered as PROSPERO no. CRD42011001370. The National Institute for Health Research Health Technology Assessment programme.

The Effects of an Uninterrupted Switch from Donepezil to Galantamine without Dose Titration on Behavioral and Psychological Symptoms of Dementia in Alzheimer's Disease

Aims: To elucidate the efficacy of galantamine on cognition and behavioral and psychological symptoms of dementia (BPSD) in outpatients with mild cognitive impairment (MCI) and Alzheimer's disease (AD) who have switched from donepezil to galantamine. Materials and Methods: We performed an uninterrupted switch from donepezil to galantamine without a washout period or dose titration in 44 ambulatory outpatients with amnestic MCI (n = 12) or mild-to-moderate AD (n = 32). Three months after the switch, the efficacy of galantamine was evaluated with the Mini-Mental State Examination (MMSE), and the Neuropsychiatric Inventory (NPI) and NPI Brief Questionnaire Form (NPI-Q), respectively, using the Wilcoxon signed-rank test. Results: NPI scores improved significantly on BPSD, especially on delusions, agitation and aberrant motor activity in AD patients (p = 0.027); improvement was remarkable in patients with moderate AD (MMSE score 10-19; p = 0.007), while insignificant in those with MCI (MMSE score ≥24; p = 0.648). The NPI-Q score also improved significantly regarding both the severity of the disease (p = 0.009) and caregiver distress (p = 0.012) in AD patients. MMSE scores hardly improved in either MCI (p = 0.394) or AD patients (p = 0.265). Conclusions: An uninterrupted switch from donepezil to galantamine could be a useful alternative treatment option for AD patients whose BPSD are unresponsive to donepezil, or whose caregivers are not satisfied with donepezil treatment.

The MOBID-2 pain scale: reliability and responsiveness to pain in patients with dementia.

BackgroundMobilization-Observation-Behavior-Intensity-Dementia-2 (MOBID-2) pain scale is a staff-administered pain tool for patients with dementia. This study explores MOBID-2's test–retest reliability, measurement error and responsiveness to change.MethodsAnalyses are based upon data from a cluster randomized trial including 352 patients with advanced dementia from 18 Norwegian nursing homes. Test–retest reliability between baseline and week 2 (n = 163), and weeks 2 and 4 (n = 159) was examined in patients not expected to change (controls), using intraclass correlation coefficient (ICC2.1), standard error of measurement (SEM) and smallest detectable change (SDC). Responsiveness was examined by testing six priori-formulated hypotheses about the association between change scores on MOBID-2 and other outcome measures.ResultsICCs of the total MOBID-2 scores were 0.81 (0–2 weeks) and 0.85 (2–4 weeks). SEM and SDC were 1.9 and 3.1 (0–2 weeks) and 1.4 and 2.3 (2–4 weeks), respectively. Five out of six hypotheses were confirmed: MOBID-2 discriminated (p < 0.001) between change in patients with and without a stepwise protocol for treatment of pain (SPTP). Moderate association (r = 0.35) was demonstrated with Cohen-Mansfield Agitation Inventory, and no association with Mini-Mental State Examination, Functional Assessment Staging and Activity of Daily Living. Expected associations between change scores of MOBID-2 and Neuropsychiatric Inventory – Nursing Home version were not confirmed.ConclusionThe SEM and SDC in connection with the MOBID-2 pain scale indicate that the instrument is responsive to a decrease in pain after a SPTP. Satisfactory test–retest reliability across test periods was demonstrated. Change scores ≥ 3 on total and subscales are clinically relevant and are beyond measurement error.

Multistimulation Group Therapy in Alzheimer’s Disease Promotes Changes in Brain Functioning

Background. The growing social emergency represented by Alzheimer’s disease (AD) and the lack of medical treatments able to modify the disease course have kindled the interest in nonpharmacological therapies. Objective. We introduced a novel nonpharmacological approach for people with AD (PWA) named Multidimensional Stimulation group Therapy (MST) to improve PWA condition in different disease domains: cognition, behavior, and motor functioning. Methods. Enrolling 60 PWA in a mild to moderate stage of the disease, we evaluated the efficacy of MST with a randomized-controlled study. Neuropsychological and neurobehavioral measures and functional magnetic resonance imaging (fMRI) data were considered as outcome measures. Results. The following significant intervention-related changes were observed: reduction in Neuropsychiatric Inventory scale score, improvement in language and memory subscales of Alzheimer’s Disease Assessment Scale–Cognitive subscale, and increased fMRI activations in temporal brain areas, right insular cortex, and thalamus. Conclusions. Cognitive-behavioral and fMRI results support the notion that MST has significant effects in improving PWA cognitive-behavioral status by restoring neural functioning.