Mild behavioral impairment domains are longitudinally associated with pTAU and metabolic biomarkers in dementia-free older adults.

BACKGROUND: The mechanisms linking mild behavioral impairment (MBI) and Alzheimer's disease (AD) have been insufficiently explored, with conflicting results regarding tau protein and few data on other metabolic markers. We aimed to evaluate the longitudinal association of the MBI domains and a spectrum of plasma biomarkers. METHODS: Our study is a secondary analysis of data from NOLAN. The longitudinal association of the MBI domains with plasma biomarkers, including pTau181, was tested using adjusted linear mixed-effects models. RESULTS: The sample comprised 359 participants (60% female, mean age: 78.3, standard deviation: 0.3 years). After 1 year, the MBI domain of abnormal perception was associated with steeper increases in plasma pTau181. Abnormal perception, decreased motivation, and impulse dyscontrol were associated with homocysteine or insulin dysregulation. DISCUSSION: Apart from the association with plasma pTau181, our results suggest that MBI might also represent metabolic dysregulation, probably contributing to dementia transition among older adults with subjective cognitive decline or mild cognitive impairment. HIGHLIGHTS: Mild behavioral impairment (MBI) psychosis was associated with steeper increases in plasma p. pTau could be a pharmacological target to treat agitation and psychosis symptoms. MBI domains were linked to metabolic dysregulation involving insulin and homocysteine.

Intervention of companion clowns in a special care unit: a 1-year pilot study.

AIMS: Our 1-year pilot study aims to compare Behavioral and Psychological Symptoms of Dementia (BPSDs): number and frequency, globally an in sub-domains, and distress, of 20 residents with dementia, during periods with companion clown intervention and BPSDs during periods without companion clown intervention. METHODS: A duo of accompanying clowns intervened 24 times for a total of 72 h (two interventions of 3 h each per week for 4 weeks, 3 months of the year spaced 13 weeks apart) in the Special Care Unit. This unit was dedicated to residents with severe BPSDs. BPSDs were measured monthly by Health Care Professional using Neuro-Psychiatric Inventory (NPI). RESULTS: Baseline NPI total score of the 20 residents (10 women, mean age 76.9 years; standard deviation, SD 8.1, 70.6% with Alzheimer's disease) was 37.5 (SD = ± 19.7). The total score of the NPI was not significantly different between the periods with the clowns (median total score at 63; 25p-75p = 57-67) and the periods without the clowns (59; 25p-75p = 43-76) (p = 0.08). Compared to the period without clowns, residents presented significantly fewer delusions, hallucinations, euphoria, aberrant motor behavior but significantly more depression, apathy, disinhibition and more appetite disorders (all p value < 0.05). No statistically significant difference was observed on the distress the symptoms caused on the HCP during periods with the clowns. CONCLUSION: Accompanying clowns may not significantly reduce the overall BPSD of the residents, but may have beneficial effects in some behavioral issues.

Agitation in Alzheimer's disease: Novel outcome measures reflecting the International Psychogeriatric Association (IPA) agitation criteria.

INTRODUCTION: The 2017 European Union-North American Clinical Trials in Alzheimer's Disease Task Force recommended development of clinician-rated primary outcome measures for Alzheimer's disease (AD) agitation trials, incorporating International Psychogeriatric Association (IPA) criteria. METHODS: In a modified Delphi process, Cohen-Mansfield Agitation Inventory (CMAI) and Neuropsychiatric Inventory-Clinician (NPI-C) items were mapped to IPA agitation domains generating novel instruments, CMAI-IPA and NPI-C-IPA. Validation in the Agitation and Aggression AD Cohort (A3C) assessed minimal clinically important differences (MCIDs), change sensitivity, and predictive validity. RESULTS: MCID was -17 (odds ratio [OR] = 14.9, 95% confidence interval [CI] = 6.8-32.6) for CMAI; -5 (OR = 9.3, 95% CI = 4.0-21.2) for CMAI-IPA; -3 (OR = 11.9, 95% CI = 4.1-34.8) for NPI-C-A+A; and -5 (OR = 7.8, 95% CI = 3.4-17.9) for NPI-C-IPA at 3 months. Areas under the curve suggested no scale better predicted global clinician ratings. Sensitivity to change for all measures was high. CONCLUSION: Internal consistency and reliability analyses demonstrated better accuracy for the NPI-C-IPA than for the CMAI-IPA and can be used for agitation clinical trial inclusion, and for response to intervention.

Health workers perception on telemedicine in management of neuropsychiatric symptoms in long-term care facilities: Two years follow-up.

The management of neuropsychiatric symptoms is a challenge in long-term care facilities. Our objective was to assess the perception of telemedicine, as a useful tool to connect staff to specialized units. In this multicenter prospective study, 90 patients from ten facilities benefited from 180 sessions over two years. The primary outcome was the perception of telemedicine evaluated through semi-structured interviews at baseline and two years later. Our results revealed positive perceptions of telemedicine, confirmed after two years of real-life experience with its use. Not only do staff members believe that telemedicine is not a downgraded version of medicine, but they also believe that it could improve the quality of care. They expressed a very positive sense of recognition of their professional qualifications and indicated their need to be involved in change processes to ensure successful implementation and better adherence to telemedicine as a service.

Potentially modifiable factors associated with agitation and aggression in Alzheimer's disease: results of the ICTUS study.

OBJECTIVES: To study potentially modifiable factors associated with the severity of agitation or aggression (A/A) symptoms among Alzheimer's disease (AD) patients. DESIGN: Data from the Impact of Cholinergic Treatment Use (ICTUS) study, European longitudinal prospective observational study. SETTING: Community dwelling outpatients included in 29 European memory clinics. PARTICIPANTS: 1375 participants with probable AD (Mini-Mental State Examination score of 10-26) with an informal caregiver. MEASUREMENTS: At baseline and twice yearly over the two-year follow-up, patients underwent comprehensive clinical and neuropsychological assessments: sociodemographic data, cognitive status, functional impairment, and assessment of neuropsychiatric symptoms based on Neuro-Psychiatric Inventory (NPI). The ZARIT scale assessed the caregiver's burden. The variable of interest was the severity of the item of A/A of the NPI. To study factors associated to the severity of A/A symptoms six months later, a multivariate mixed regression model was used. RESULTS: Frequency of A/A symptom varied from 30% to 34% at each visit. Two factors were found to be independently associated with the severity of A/A: (1) the presence of affective disorder (anxiety, depression, and/or irritability) that increased the severity of the A/A by 0.89 point (coefficient:0.89; 95% Confidence Interval (CI) = [0.48,1.30], p < 0.001), and (2) a severe caregiver burden that increased the severity of the A/A by 1.08 point (coefficient:1.08; 95% CI = [0.69,1.47], p < 0.001). CONCLUSION: Research should evaluate whether the identification and treatment of an affective disorder along with the evaluation and optimal management of the caregiver would have a positive impact on the course of A/A in mild to moderate AD patients.

Coronavirus Disease-2019 in Older People with Cognitive Impairment.

Patients with cognitive impairment have paid a heavy price for the coronavirus disease 2019 pandemic. Their clinical characteristics and their place of life made them particularly exposed to being infected and suffering from severe forms. The repercussions of the isolation measures also had significant repercussions on the expression of their neuropsychiatric symptoms and the burden on families and health care professionals.

Antidepressant Use and Progression of Mild to Moderate Alzheimer's Disease: Results from the European ICTUS Cohort.

OBJECTIVES: Neuropsychiatric symptoms (NPS) are a core and troubling feature among patients with Alzheimer disease (AD). Because of growing safety warnings against antipsychotics, the use of antidepressants (ATD) in AD has increased extensively. We investigated the potential long-term associations between ATD exposure and functional and cognitive progression in patients with mild to moderate AD. DESIGN: Two-year prospective multicenter cohort ICTUS (Impact of Cholinergic Treatment USe) study with biannual assessments. SETTING: Twenty-nine memory clinics from 12 European countries. PARTICIPANTS: Community-dwelling patients with mild to moderate AD. METHODS: Global cognitive function was measured using the Mini Mental State Examination (MMSE) and the Alzheimer's Disease Assessment Scale-Cognitive Subscale (ADAS-Cog). Functional impairment was measured using the Activities of Daily Living (ADL). Assessments were performed biannually for 2 years. Antidepressant exposure was defined by an ATD prescription for a minimum period of 6 months. Linear mixed models were used to study the associations between ATD exposure and cognitive and functional progression. RESULTS: Antidepressant exposure was not associated with cognitive decline [MMSE: ß-coefficients of the linear mixed models (Coef) = 0.06, 95% confidence interval (CI) -0.65 to 0.76, P = .87; ADAS-Cog: Coef = -13.9, 95% CI -34.80 to 7.03, P = .19] or with functional decline (ADL: Coef = -0.05, 95% CI -0.21 to 0.09, P = .48) at 2-year follow-up. Antipsychotic exposure at baseline was associated with a greater functional decline in the ADL score (Coef = -0.39, 95% CI - 0.68 to 0.10, P < .01). CONCLUSIONS AND IMPLICATIONS: Antidepressant exposure was not associated with a faster rate of cognitive or functional decline in patients with mild to moderate AD. Antidepressants might be appropriate alternatives to antipsychotics in the management of NPS in mild to moderate AD.

Depression in People With Dementia and Caregiver Outcomes: Results From the European Right Time Place Care Study.

OBJECTIVE: To investigate the cross-sectional associations between depression in people with dementia and both caregiver burden and quality of life in 8 European countries, and to test these associations compared with the presence of other neuropsychiatric symptoms. DESIGN: Cross-sectional study. SETTING AND PARTICIPANTS: In total, 1223 dyads comprised of informal caregivers and people with dementia living in a community-dwelling setting, recruited from the Right Time Place Care study, a cohort survey from 8 European countries. MEASURES: To test the associations between depression (according to the Cornell Scale for Depression in Dementia) and informal caregiver burden (defined by the Zarit scale and hours of supervision in terms of Resource Utilization in Dementia), distress (defined by the Neuropsychiatric Inventory Questionnaire distress score), and quality of life (according to the visual analogue scale and 12-item General Health Questionnaire). RESULTS: Linear regressions showed an association between depression and main outcomes (Zarit scale: ß 3.7; P = .001; hours of supervision: ß 1.7; P = .004; Neuropsychiatric Inventory Questionnaire distress score: ß 1.2; P = .002). A similar association was found concerning psychological and overall well-being (12-item General Health Questionnaire: ß 1.8; P < .001; Euroqol Visual Analogue Scale: ß -4.1; P = .003). Both associations remained significant despite the presence of other NPS and after adjusting for confounders. CONCLUSIONS AND IMPLICATIONS: Further studies are needed to assess whether providing tailored strategies for optimizing diagnosis and managing of depression in people with dementia might improve caregiver quality of life and reduce their burden in the community-dwelling setting.

Neuropsychiatric Symptoms and Risk of Progression to Alzheimer's Disease Among Mild Cognitive Impairment Subjects.

BACKGROUND: Neuropsychiatric symptoms (NPS) are prevalent in mild cognitive impairment (MCI), but we do not know much about their role in progression to dementia. OBJECTIVE: To investigate NPS and the risk of progression to probable Alzheimer's disease dementia (AD) among subjects with MCI. METHODS: 96 MCI participants were followed for 4 years. Progression to probable AD was defined by the change of CDR total score from 0.5 to ≥1, reviewed by an expert consensus panel. NPS were determined using the Neuropsychiatric Inventory (NPI) 12-items. This study analyzed prognostic value of each NPI item and 5 sub-syndromes of NPS (apathy, psychosis, affective, hyperactivity, and vegetative) for prediction of progression to probable AD. A Cox proportional hazard model was used; hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated with time dependent variable to compare the incidence of progression considering presence/absence of any NPS or sub-syndromes throughout the study. RESULTS: The presence of symptoms "agitation/aggression", "delusions", and "aberrant motor behavior" significantly increased the risk of probable AD (HR = 3.9; 95% CI = 1.9-8.2; HR = 13.9; 95% CI = 4.1-48.9; HR = 4.3; 95% CI = 1.7-10.3, respectively). The presence of sub-syndromes "psychosis" and "hyperactivity" were also predictors of progression (HR = 14.0; 95% CI = 4.4-44.5; HR = 2.0; 95% CI = 1.1-3.7, respectively). These results did not change after adjusting by potential confounders. CONCLUSION: Presence of delusions, agitation/aggression, and aberrant motor behavior is predictor of progression to probable AD.

Telemedicine for the management of neuropsychiatric symptoms in long-term care facilities: the DETECT study, methods of a cluster randomised controlled trial to assess feasibility.

INTRODUCTION: Neuropsychiatric symptoms (NPSs) in elderly patients with dementia are frequent in long-term care facilities (LTCFs) and are associated with adverse events. Telemedicine is an emerging way to provide consultation and care to dependent LTCF residents who may not have easy access to specialty services. Several studies have evaluated telemedicine for dementia care but to date, no study has evaluated its impact in the management of NPS in patients with dementia living in LTCF. METHODS AND ANALYSIS: The Dementia in long-term care facilities: Telemedicine for the management of neuropsychiatric symptoms (DETECT) study is a 24-month multicentre prospective cluster randomised controlled study with two arms: a control arm (usual care) and an intervention arm (telemedicine consultation) for NPSs management. DETECT enrolled 20 LTCFs. The primary outcome is based on the acceptability of the telemedicine among the LTCF staff which will be assessed in the intervention group by quantitative and qualitative indicators. The rate of unscheduled hospitalisations and/or consultations due to disruptive NPSs, psychotropic drug use and health costs will be described in both groups. Approximately, 200 patients are expected to be recruited. ETHICS AND DISSEMINATION: The study protocol was approved and sponsored by the French Ministry of Health. The study received ethical approval from the Toulouse University Hospital Institutional Review Board. We will communicate the final results to the public via conferences and results will also be submitted for publication in international peer-reviewed scientific journals. TRIAL REGISTRATION NUMBER: NCT02472015.

Costs of Care of Agitation Associated With Dementia in 8 European Countries: Results From the RightTimePlaceCare Study.

OBJECTIVE: To estimate the additional societal costs for people living with dementia (PwD) with agitation in home care (HC) and institutional long-term care (ILTC) settings in 8 European countries. DESIGN: Cross-sectional data from the RightTimePlaceCare cohort. SETTING: HC and ILTC settings from 8 European countries (Estonia, Finland, France, Germany, Netherlands, Spain, Sweden, and England). PARTICIPANTS: A total of 1997 PwD (1217 in HC group and 780 lived in an ILTC) and their caregivers. MAIN OUTCOME MEASURES: Medical care, community care, and informal care were recorded using the Resource Utilization in Dementia (RUD) questionnaire. Agitation was assessed based on the agitation symptoms cluster defined by the presence of agitation and/or irritability and/or disinhibition and/or aberrant motor behavior items of the Neuropsychiatric Inventory Questionnaire (NPI-Q). RESULTS: Total monthly mean cost differences due to agitation were 445€ in the HC setting and 561€ in the ILTC setting (P = .01 and .02, respectively). Informal care costs were the main driver in the HC group (73% of total costs) and institutional care costs were the main driver in the ILTC group (53% of total costs). After adjustments, the log link generalized linear mixed model showed an association between agitation symptoms and an increase of informal care costs by 17% per month in HC setting (P < .05). CONCLUSION: This study found that agitation symptoms have a substantial impact on informal care costs in the community care setting. Future research is needed to evaluate which strategies may be efficient by improving the cost-effectiveness ratio and reducing the burden associated with informal care in the management of agitation in PwD.

Associated factors with antipsychotic use in long-term institutional care in eight European countries: Results from the RightTimePlaceCare study.

OBJECTIVES: To determine factors associated with the antipsychotic (AP) prescription for people with dementia (PwD) recently admitted to institutional long-term care facilities (LTCFs) and to ascertain differences in the use of this medication in 8 European countries. DESIGN: An exploratory cross-sectional study. SETTING: LTCFs from 8 European countries (Estonia, Finland, France, Germany, The Netherlands, Spain, Sweden, and England). PARTICIPANTS: A total of 791 PwD recently admitted to an LTCF and their caregivers. MEASUREMENTS: Baseline data from RightTimePlaceCare survey was used. Patients' medical conditions, neuropsychiatric symptoms, physical and cognitive status, and medications were recorded. Multiple logistic regression models were used to assess associations with the AP use. RESULTS: A group of 296 patients (37.4%) of 791 patients recently admitted received AP medication. The prevalence of the use of 1 or more APs varied between study countries, ranging from 12% in Sweden to 54% in Spain. Factors independently associated with the AP use were living in Sweden [odds ratio (OR) 0.12, 95% confidence interval (CI) 0.05-0.30], Finland (OR 0.26, 95% CI 0.14-0.48), Germany (OR 2.75, 95% CI 1.55-4.86) and Estonia (OR 6.79, 95% CI 3.84-12.0). The odds of AP use decreased with the presence of a dementia specific unit in the LTCF (OR 0.60, 95% CI 0.39-0.92), but was higher among residents with a hyperactivity behavior (OR 2.12, 95% CI 1.41-3.18). CONCLUSION: The current study shows that more than one-third of the residents recently admitted received APs and that prescription frequency across countries varied significantly. This study raises the possibility that the presence of a dementia-specific unit might play a role in the AP use. Further studies should investigate this association and seek better understanding of what will achieve optimal quality of AP use among newly admitted residents in LTCF.