Alzheimer’s disease (AD) is an escalating global challenge, with more than 40 million people affected, and this number is projected to increase to more than 100 million by 2050. While amyloid-targeting antibody treatments (lecanemab and donanemab) are a significant step forward, the benefits of these therapies remain limited. This highlights the necessity for safe and effective compounds that offer greater therapeutic benefits to the majority of individuals with or at risk of AD. Drug repurposing allows for a cost-effective, time-efficient strategy to accelerate the availability of treatments, owing to the availability of safety information. This study focuses on the third iteration of the Delphi consensus programme aimed at identifying new high-priority drug candidates for repurposing in AD. An international expert panel comprising academics, clinicians and industry representatives was convened. Through a combination of anonymized drug nominations, systemic evidence reviews, iterative consensus rankings, and lay advisory inputs, drug candidates were evaluated and ranked based on rational, non-clinical, and clinical evidence and overall safety profiles. Among the 80 candidates that were nominated by the expert panel, seven underwent review, with only three candidates meeting the following consensus criteria of relevant mechanisms for targeting neurodegenerative pathways, non-clinical efficacy, and tolerability in older individuals. The three agents were: [1] the live attenuated herpes zoster (HZ) vaccine (Zostavax) [2], sildenafil, a phosphodiesterase-5 (PDE-5) inhibitor, and [3] riluzole, a glutamate antagonist. The HZ vaccine additionally offers potential for population-level dementia risk reduction. This Delphi consensus identified three high-priority drug repurposing candidates for AD with favourable safety profiles and mechanistic plausibility, which are considered suitable for pragmatic clinical trials, including remote or hybrid designs. The PROTECT platform, which supports international cohorts in the UK, Norway, and Canada, offers a well-established means to conduct such trials effectively, thus helping to accelerate the evaluation and potential deployment of these drug candidates to benefit individuals with or at risk for AD.

Alzheimer’s disease psychosis (ADP) produces a significant burden for patients and their care partners, but at present there are no approved treatments for ADP. The lack of approved treatments may be due to the challenges of conducting clinical trials for this disease. This perspective article discusses distinct challenges and proposed solutions of conducting ADP trials involving seven key areas: (1) methods to reduce the variable and sometimes high rates of placebo response that occur for treatments of neuropsychiatric symptoms; (2) the use of combined or updated criteria that provide a precise, consensus definition of ADP; (3) the use of eligibility criteria to help recruit individuals representative of the larger ADP population and overcome the difficulty of recruiting patients with moderate-to-severe ADP; (4) consideration of multiple perspectives and implementation of technology to reduce the variability in the administration and scoring of neuropsychiatric symptom assessments; (5) the use of clinically appropriate, a priori–defined severity thresholds and responder cutoffs; (6) the use of statistical approaches that address absolute effect sizes and a three-tier approach to address the fluctuation of neuropsychiatric symptoms; and (7) the implementation of feasible diagnostic and target-engagement biomarkers as they become available. The goal of these proposed solutions is to improve the evaluation of potential ADP therapies, within the context of randomized, placebo-controlled trials with clinically meaningful endpoints and sustained treatment responses.

OBJECTIVES:This study aimed to determine the impact of the Covid-19 pandemic on neuropsychiatric symptoms and antipsychotic use in people with dementia living in nursing homes. METHODS:This was a comparative analysis of baseline data from two large nursing home studies, one conducted during (COVID-iWHELD study) and one prior (WHELD study) to the pandemic. It involves data from 69 and 149 nursing homes, and 1006 and 666 participants respectively. Participants were people with established dementia (score >1 on Clinical Dementia Rating Scale). Resident data included demographics, antipsychotic prescriptions and neuropsychiatric symptoms using the Neuropsychiatric Inventory Nursing Home version. Nursing home data collected were nursing home size and staffing information. RESULTS:Overall prevalence of neuropsychiatric symptoms was unchanged from pre-pandemic prevalence. Mean antipsychotic use across the sample was 32.0%, increased from 18% pre-pandemic (Fisher's exact test p < 0.0001). At a nursing home level, the medians for the low, medium and high tertiles for antipsychotic use were 7%, 20% and 59% respectively, showing a disproportionate rise in tertile three. Residents in these homes also showed a small but significant increase in agitation. CONCLUSION:There has been a significant increase in antipsychotic prescribing in nursing homes since the COVID-19 pandemic, with a disproportionate rise in one third of homes, where median prescription rates for antipsychotics were almost 60%. Strategies are urgently needed to identify these nursing homes and introduce pro-active support to bring antipsychotic prescription rates back to pre-pandemic levels.

New ministerial decree restricts driving motorized vehicles for patients with Alzheimer's disease and related disorders. Reisberg stage 3, threshold used to contraindicate driving, appears to correspond to a mild stage of major neurocognitive impairment. A single scale gives an idea of the level of risk but does not provide a holistic assessment. The aim of this consensus is to put forward recommendations from several French learned societies for individualized cognitive assessments to minimize the risks associated with driving and its cessation. Fitness to drive should be raised at the earliest stages of the diagnostic process, and regularly throughout the follow-up. Consult a registered doctor is recommended to all patients wishing to continue driving. All documents must be given to the patient only. An alternative must always be offered to patients who are recommended a modal shift.

The publication of the decree on the care of people with neurocognitive disorders brought to the fore the Reisberg's Global Deterioration Scale, a scale that only few clinicians use in memory centers or in geriatric. This scale has a number of limitations, not least of which is that it is obsolete, since it does not take into account disease advances in scientific knowledge with biomarkers. Consequently, the stages evoked no longer correspond to current descriptions. Moreover, it only concerns Alzheimer's disease, whereas in our practice we encounter other neurodegenerative pathologies. Even if we decide to use another global assessment scale, such as the Clinical Dementia Rating or the Functional Assessment Staging, they cannot replace a personalized assessment. Indeed, it is important to stress that this decree does not take into account the relevance of personalized assessments using, for example, neuropsychological tests to estimate driving ability. A personalized assessment accompanied by a real-life driving test would be preferable than a score on a global scale. This article therefore presents the Global Deterioration Scale, highlighting its unsuitability for assessing whether or not to continue driving.

OBJECTIVES:Nursing Home Placement (NHP) can prove to be the only solution to some dead-end situations in Alzheimer's disease (AD). The predictors of NHP are known and can be related to either the person with dementia or his/her caregiver. We aimed to identify predictors of NHP among people with AD over a 2-year follow-up period, with a particular interest in the modifiable predictors, notably those involving caregivers. METHODS:We studied data from the THERAD study, a French monocentric randomized controlled trial, involving 196 community-dwelling dyads, primarily assessing an educational intervention in AD. We performed a bivariate analysis followed by a multivariate Cox model, with a backward stepwise procedure. RESULTS:The mean age of the patients was 82 years old, 67.7% were women and 56.9% were living with a partner. The mean age of the caregivers was 65.8 years old, 64.6% were women and half were spouses of the patients with a moderate burden. During the follow-up, 23 patients died and 49 were institutionalized. The majority of NHPs occurred during the first year (35 NHP). The mean time to NHP was 27.77 months after the diagnosis. Five independent predictors of NHP were found: a higher patient education level (aHR 6.31; CI95% = 1.88-21.22), a high caregiver Burden (aHR 3.97; CI95% = 1.33-11.85), the caregiver being the offspring of the patient (aHR 2.92; CI95% = 1.43-5.95), loss of autonomy (aHR 2.75; CI95% = 1.13-6.65) and disinhibition as a behavioural and psychological symptoms of dementia (BPSD) (aHR 2.38; CI95% = 1.26-4.47). CONCLUSIONS:Our data are in accordance with the literature in identifying loss of autonomy, burden and BPSD (disinhibition) as risk factors of NHP. We also found high patient education level and status of offspring caregiver as additional factors. It is essential to take into account the caregiver status when designing psychoeducational trials aiming to delay NHP. Further studies need to take into account both the modifiable risk factors related to the patient (productive BPSD) and the needs of offspring caregivers (work-life balance, mental load).

Patients with dementia can experience hallucinations and delusions because of their underlying neurodegenerative condition, a syndrome known as dementia-related psychosis. Dementia-related psychosis contributes to morbidity and mortality among patients with dementia and increases the burden on caregivers and the health care system. With no pharmacological treatment currently approved in the United States for this condition, patients are often treated off-label with antipsychotics. Though typical and atypical antipsychotics have demonstrated variable to modest efficacy in dementia-related psychosis, serious safety concerns arise with their use. Accordingly, clinical and Centers for Medicare & Medicaid Services guidelines recommend trying antipsychotics only when other therapies have failed and encourage treatment discontinuation of antipsychotics after 4 months to assess whether ongoing therapy is needed. Discontinuation of effective antipsychotic treatment, however, may increase the risk for relapse of symptoms and the associated morbidities that accompany relapse. A randomized medication withdrawal clinical trial design allows assessment of relapse risk after discontinuation and can provide initial information on longer-term safety of therapy for dementia-related psychosis. Given the substantial unmet need in this condition, new, well-tolerated therapies that offer acute and sustained reduction of symptoms while also preventing recurrence of symptoms of psychosis are critically needed.

Background Although educational interventions are recommended in Alzheimer’s disease (AD), studies assessing the impact of interventions such as “therapeutic patient education” are scarce. Indeed, the intrinsic nature of the disease is considered a barrier to patients’ involvement in such approaches. We aimed to evaluate an intervention by using a “dyadic” approach (patient and caregiver) in both intervention and assessment. Methods THERAD is a monocentric, randomized, controlled trial assessing the effects of a 2-month educational programme in mild to moderately severe AD patients among 98 dyads (caregiver/patient) on caregiver-reported patient quality of life (QOL) at 2 months. Community-dwelling patients and their caregivers were recruited in ambulatory units of the French Toulouse University Hospital. Self-reported patient QOL, autonomy, behavioural and psychological symptoms and caregiver QOL and burden were collected at 2, 6 and 12 months. Linear mixed models were used in modified intention-to-treat populations. We also performed sensitivity analysis. Results A total of 196 dyads were included, 98 in each group. The mean age of the patients was 82 years, 67.7% were women, diagnosed with AD (+/- cerebrovascular component) (mean MMSE =17.6), and 56.9% lived with a partner. The mean age of the caregivers was 65.7 years, and 64.6% were women (52.3% offspring/42.6% spouses), with a moderate burden (mean Zarit score = 30.9). The mean caregiver-reported patient QOL was lower than the self-reported QOL (28.61 vs. 33.96). We did not identify any significant difference in caregiver-reported patients’ QOL ( p = 0.297) at 2 months, but there was a significant difference in self-reported patients’ QOL at 2 months ( p = 0.0483) or 6 months ( p = 0.0154). No significant difference was found for the secondary outcomes. The results were stable in the sensitivity analyses. Conclusions This randomized controlled trial assessing an educational intervention in 196 dyads (Alzheimer’s disease affected patient/caregiver) highlights the need to better consider the patient’s point of view, since only the self-reported QOL was improved. Additional studies using this dyadic approach are necessary in targeted subpopulations of caregivers (spouse vs. child, gender) and of patients (severity of cognitive impairment or behavioural disturbances) Trial registration THERAD study NCT01796314. Registered on February 19, 2013.

What the COVID pandemic entails for the management of patients with behavioral and psychological symptoms of dementia: experience in France. The behavioral and psychological symptoms of dementia (BPSD) are well-known in patients with major cognitive impairment(1). The Covid 19 pandemic calls into question the organization of Cognitive and Behavioral Units (CBU) specialized in the management of BPSD (2)(3) to limit the risk of contamination for hospitalized patients and staff. Moderate to severe cognitive disorders and BPSDs such as wandering and agitation explain patients’ lack of understanding of the basic protective measures against Covid and their difficulty in implementing them (4). It is also difficult to find the right balance between protective but coercive measures and respect for patients’ dignity. Another difficulty is how to streamline hospital procedures to reduce workload and limit the risk of mental and physical exhaustion.

Background: Evidence is lacking on the differences between hospitalisation of people with dementia living in nursing homes and those living in the community. The objectives of this study were: 1) to describe the frequency of hospital admission among people with dementia in eight European countries living in nursing homes or in the community, 2) to examine the factors associated with hospitalisation in each setting, and 3) to evaluate the costs associated with it. Methods: The present study is a secondary data analysis of the RightTimePlaceCare European project. A cross-sectional survey was conducted with data collected from people with dementia living at home or who had been admitted to a nursing home in the last three months, as well as from their caregivers. Data on hospital admissions at three months, cognitive and functional status, neuropsychiatric symptoms, comorbidity, polypharmacy, caregiver burden, nutritional status, and falls were assessed using validated instruments. Multivariate regression models were used to investigate the factors associated with hospital admission for each setting. Costs were estimated by multiplying quantities of resources used with the unit cost of each resource and inflated to the year 2019. Results : The study sample comprised 1,700 people with dementia living in the community and nursing homes. Within three months, 13.8% and 18.5% of people living in nursing homes and home care, respectively, experienced ≥1 hospital admission. In the nursing home setting, only polypharmacy was associated with a higher chance of hospital admission, while in the home care setting, unintentional weight loss, polypharmacy, falls, and more severe caregiver burden were associated with hospital admission. Overall, the estimated average costs per person with dementia/year among participants living in a nursing home were lower than those receiving home care. Conclusion: Admission to hospital is frequent among people with dementia, especially among those living in the community, and seems to impose a remarkable economic burden. The identification and establishment of an individualised care plan for those people with dementia with polypharmacy in nursing homes, and those with involuntary weight loss, accidental falls, polypharmacy and higher caregiver burden in the home care setting, might help preventing unnecessary hospital admissions.

Health care systems face an expansion in the number of older individuals with a high prevalence of neurodegenerative diseases and related behavioral and psychological symptoms of dementia (BPSDs). Health care providers are expected to develop innovative solutions to manage and follow up patients over time in the community. To date, we are unable to continuously and accurately monitor the nature, frequency, severity, impact, progression, and response to treatment of BPSDs after the initial assessment. Technology could address this need and provide more sensitive, less biased, and more ecologically valid measures. This could provide an opportunity to reevaluate therapeutic strategies more quickly and, in some cases, to treat earlier, when symptoms are still amenable to therapeutic solutions or even prevention. Several studies confirm the relationship between sensor-based data and cognition, mood, and behavior. Most scientific work on mental health and technologies supports digital biomarkers, not so much as diagnostic tools but rather as monitoring tools, an area where unmet needs are significant. In addition to the implications for clinical care, these real-time measurements could lead to the discovery of new early biomarkers in mental health. Many also consider digital biomarkers as a way to better understand disease processes and that they may contribute to more effective pharmaceutical research by (i) targeting the earliest stage, (ii) reducing sample size required, (iii) providing more objective measures of behaviors, (iv) allowing better monitoring of noncompliance, (v) and providing a better understanding of failures. Finally, communication technologies provide us with the opportunity to support and renew our clinical and research practices.

Dementia is a syndrome, with a wide range of symptoms. It is important to have a timely diagnosis during the disease course to reduce the risk of medication errors, enable future care planning for the patient and their relatives thereby optimizing quality of life (QoL). For this reason, it is important to avoid a diagnosis of dementia not otherwise specified (DNOS) and instead obtain a diagnosis that reflects the underlying pathology. The aim of this study was to investigate the prevalence and associated factors of DNOS in persons with dementia living at home or in a nursing home. This is a cross-sectional cohort study performed in eight European countries. Persons with dementia aged ≥65 years living at home (n = 1223) or in a nursing home (n = 790) were included. Data were collected through personal interviews with questionnaires based on standardised instruments. Specific factors investigated were sociodemographic factors, cognitive function, and mental health, physical health, QoL, resource utilization and medication. Bivariate and backward stepwise multivariate regression analyses were performed. The prevalence of DNOS in the eight participating European countries was 16% (range 1–30%) in persons living at home and 21% (range 1–43%) in persons living in a nursing home. These people are more often older compared to those with a specific dementia diagnosis. In both persons living at home and persons living in a nursing home, DNOS was associated with more severe neuropsychiatric symptoms and less use of anti-dementia medication. In addition, persons with DNOS living at home had more symptoms of depression and less use of antidepressant medication. The prevalence of DNOS diagnosis is common and seems to vary between European countries. People with DNOS are more often older with more severe neuropsychiatric symptoms and receive fewer anti-dementia medication, anxiolytics and antidepressants. This would support the suggestion that a proper and specific diagnosis of dementia could help the management of their disease.

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.

For the second time in the past 3 years, the EU-US CTAD Task Force addressed challenges related to designing clinical trials for agitation in dementia, which is one of the most disruptive aspects of the condition for both patients and caregivers. Six recommendations emerged from the Task Force meeting: 1 – Operationalizing agitation criteria established by the IPA; 2 – Combining clinician- and caregiver-derived outcomes as primary outcome measures; 3 – Using global ratings to define clinically meaningful effects and power studies; 4 – Improving the accuracy of caregiver reports by better training and education of caregivers; 5 – Employing emerging technologies to collect near real-time behavioral data; and 6 – Utilizing innovative trial designs and increasing the use of biomarkers to maximize the productivity of clinical trials for neuropsychiatric symptoms.

Objectives: to evaluate the frequency of potentially inappropriate medication (PIM) prescription among older people with dementia (PwD) from eight countries participating in the European study 'RightTimePlaceCare', and to evaluate factors and adverse outcomes associated with PIM prescription. Methods: survey of 2,004 PwD including a baseline assessment and follow-up after 3 months. Interviewers gathered data on age, sex, prescription of medication, cognitive status, functional status, comorbidity, setting and admission to hospital, fall-related injuries and mortality in the time between baseline and follow-up. The European Union(7)-PIM list was used to evaluate PIM prescription. Multivariate regression analysis was used to investigate factors and adverse outcomes associated with PIM prescription. Results: overall, 60% of the participants had at least one PIM prescription and 26.4% at least two. The PIM therapeutic subgroups most frequently prescribed were psycholeptics (26% of all PIM prescriptions) and 'drugs for acid-related disorders' (21%). PwD who were 80 years and older, lived in institutional long-term care settings, had higher comorbidity and were more functionally impaired were at higher risk of being prescribed two PIM or more. The prescription of two or more PIM was associated with higher chance of suffering from at least one fall-related injury and at least one episode of hospitalisation in the time between baseline and follow-up. Conclusions: PIM use among PwD is frequent and is associated with institutional long-term care, age, advanced morbidity and functional impairment. It also appears to be associated with adverse outcomes. Special attention should be paid to psycholeptics and drugs for acid-related disorders.

BackgroundHealth promotion programs could prevent and delay frailty and functional decline. However, in practice, the planning and establishment of such a program is a challenge for health care providers. We report an experimental model of screening and management for frail elderly conducted in Cugnaux, city of 16,638 inhabitants in France, by the Toulouse Gerontopole and the social care service of the Cugnaux City Hall.MethodsA frailty screening self-administered questionnaire (FiND questionnaire) was sent to communitydwelling residents of 70 years old and over of Cugnaux. The completed questionnaires were analyzed and the subjects were classed into three groups: robust, frail, mobility disability, based on their score. Frail subjects and those with mobility disability invited to undergo a frailty assessment in the premises of the town hall realized by a nurse in order to identify the causes of their frailty and propose them a personalized intervention plan (PIP).ResultsThe FiND questionnaire was sent to the residents of Cugnaux of 70 years old and over (n=2,003). After two mailings, 860 (42.9%) completed questionnaires were received. Mean age of the responders was 79.0 ± 6.2 years and 59.6% women (n= 511). According to the questionnaires analysis, 393 (45.7%) were robust, 212 (24.6%) frail, 240 (27.9%) had a mobility disability and 15 (1.7%) could not be classified due to missing data. 589 (68.5%) subjects accepted to be contacted by the Gerontopole nurse. The assessment by the nurse was proposed to frail subjects and those with mobility disability (n=313). Until 31 December 2016, 136 patients have been evaluated. The mean age was 80.1±5.4 and most patients were women (69.9%). The mean ADL score was 5.8±0.5 and the IADL showed a mean score of 6.9±1.7. According to Fried definition of frailty, 76 patients (55.9%) were pre-frail, and 35 (25.7%) frail. Concerning the frailty domains identified, 75 patients (55.1%) showed the alteration of physical performance, 70 (51.5%) thymic disorders and 46 (33.8%) sensory disorders. Preventive interventions proposed in the PIP were mostly physical interventions (86.8%, n=118) followed by cognitive (61.8%, n=84) and nutritional (39.7%, n=54) interventions.DiscussionThis project shows the feasibility to implement a care model in the community. It permitted a large identification of frail elderly people in the city population, insuring their assessment and clinical follow up to maintain their capacities and referring them to social services.

Objectives: To investigate informal caregivers' psychological well-being and predicted increase in psychological well-being, when caring for persons with dementia (PwDs) living at home, related to caregiver, PwD and formal care (FC) factors.Method: A cohort study at baseline and 3 months' follow-up in eight European countries. Caregivers included (n = 1223) were caring for PwDs aged >= 65 years at home. Data on caregivers, PwDs and FC were collected using standardized instruments. Regression analysis of factors associated with caregiver psychological well-being at baseline and 3 months later was performed.Results: Factors associated with caregiver psychological well-being at baseline were positive experience of caregiving, low caregiver burden, high quality of life (QoL) for caregivers, male gender of PwD, high QoL of PwD, few neuropsychiatric symptoms and depressive symptoms for the PwD. At follow-up, caregivers with increased psychological well-being experienced of quality of care (QoC) higher and were more often using dementia specific service. Predicting factors for caregivers' increased psychological well-being were less caregiver burden, positive experience of caregiving, less supervision of the PwD and higher caregiver QoL, if PwD were male, had higher QoL and less neuropsychiatric symptoms. Furthermore, higher QoC predicted increased caregivers' psychological well-being.Conclusion: Informal caregiving for PwDs living at home is a complex task. Our study shows that caregivers' psychological well-being was associated with, among other things, less caregiver burden and higher QoL. Professionals should be aware of PwD neuropsychiatric symptoms that might affect caregivers' psychological well-being, and provide proper care and treatment for caregivers and PwDs.

In European countries, knowledge about availability and utilization of support for informal caregivers caring for older persons (≥65 years) with dementia (PwD) is lacking. To be able to evaluate and develop the dementia support system for informal caregivers to PwD, a survey of European support systems and professionals involved is needed. The aim of this study was to explore support for informal caregivers to PwD in European countries. We investigated the availability and utilization of support in each of the participating countries, and the professional care providers involved, through the dementia disease.

Objectives: In European countries knowledge about availability and utilisation of support for informal caregivers caring for older person with dementia (PwD) is lacking. To be able to evaluate and ...

Objectives: To investigate persons with dementia and their informal caregivers’ views of inter-sectoral information, communication and collaboration throughout the trajectory of dementia care, in e ...