Cholinesterase inhibitors and memantine are associated with a reduced mortality in nursing home residents with dementia: a longitudinal observational study.

BACKGROUND: A large proportion of nursing home (NH) residents suffer from dementia and effects of conventional anti-dementia drugs on their health is poorly known. We aimed to investigate the associations between exposure to anti-dementia drugs and mortality among NH residents. METHODS: This retrospective longitudinal observational study involved 329 French NH and the residents admitted in these facilities since 2014 and having major neurocognitive disorder. From their electronic health records, we obtained their age, sex, level of dependency, Charlson comorbidity index, and Mini mental examination score at admission. Exposure to anti-dementia drugs was determined using their prescription into 4 categories: none, exposure to acetylcholinesterase inhibitors (AChEI) alone, exposure to memantine alone, exposure to AChEI and memantine. Survival until the end of 2019 was studied in the entire cohort by Cox proportional hazards. To alleviate bias related to prescription of anti-dementia drugs, we formed propensity-score matched cohorts for each type of anti-dementia drug exposure, and studied survival by the same method. RESULTS: We studied 25,358 NH residents with major neurocognitive disorder. Their age at admission was 87.1 + 7.1 years and 69.8% of them were women. Exposure to anti-dementia drugs occurred in 2,550 (10.1%) for AChEI alone, in 2,055 (8.1%) for memantine alone, in 460 (0.2%) for AChEI plus memantine, whereas 20,293 (80.0%) had no exposure to anti-dementia drugs. Adjusted hazard ratios for mortality were significantly reduced for these three groups exposed to anti-dementia drugs, as compared to reference group: HR: 0.826, 95%CI 0.769 to 0.888 for AChEI; 0.857, 95%CI 0.795 to 0.923 for memantine; 0.742, 95%CI 0.640 to 0.861 for AChEI plus memantine. Results were consistent in propensity-score matched cohorts. CONCLUSION: The use of conventional anti-dementia drugs is associated with a lower mortality in nursing home residents with dementia and should be widely used in this population.

Clinical impact of an individualised clinical pharmacy programme into the memory care pathway of older people: an observational study.

BACKGROUND: In older patients, medication exposure [i.e. polypharmacy, potentially inappropriate medications (PIMs), medications with anticholinergic and/or sedative properties] is a modifiable risk factor associated with cognitive iatrogenic risk and dementia. AIM: To assess the potential clinical impact of the implementation of an individualised clinical pharmacy programme at the initiation of the Memory care pathway in older patients with a cognitive complaint. METHOD: This prospective observational study included older patients with high-risk of adverse drug event (HR) admitted in a French geriatric university hospital to explore the cognitive complaint or the cognitive disorder between January and November 2021. Drug-related problems (DRPs) were identified during a medication review performed in HR patients, and pharmaceutical interventions (PIs) notified in the patient's hospitalisation report were collected. The clinical impact of PIs was assessed by an expert panel (geriatricians and clinical pharmacists) using the Clinical, Economic, and Organisational (CLEO) tool. RESULTS: Overall, 326 patients were eligible and 207 (63.5%) were considered as HR patients. Among HR patients, 88.9% (n = 184) were treated using at least 5 medications (polypharmacy), and 36.7% (n = 76) received at least one PIM with cognitive iatrogenic risk. During the medication review, 490 PIs were provided and their clinical impact was rated as minor for 57.3% (n = 281), moderate for 26.7% (n = 131), and major for 2.5% (n = 12). CONCLUSION: The integration of clinical pharmacist secured the Memory care pathway of older patients with a cognitive complaint by identifying an important number of DRPs and PIMs with potential cognitive iatrogenic risk.

Anodal transcranial direct current stimulation does not enhance the effects of motor imagery training of a sequential finger-tapping task in young adults.

When applied over the primary motor cortex (M1), anodal transcranial direct current stimulation (a-tDCS) could enhance the effects of a single motor imagery training (MIt) session on the learning of a sequential finger-tapping task (SFTT). This study aimed to investigate the effect of a-tDCS on the learning of an SFTT during multiple MIt sessions. Two groups of 16 healthy young adults participated in three consecutive MIt sessions over 3 days, followed by a retention test 1 week later. They received active or sham a-tDCS during a MIt session in which they mentally rehearsed an eight-item complex finger sequence with their left hand. Before and after each session, and during the retention test, they physically repeated the sequence as quickly and accurately as possible. Both groups (i) improved their performance during the first two sessions, showing online learning; (ii) stabilised the level they reached during all training sessions, reflecting offline consolidation; and (iii) maintained their performance level one week later, showing retention. However, no significant difference was found between the groups, regardless of the MSL stage. These results emphasise the importance of performing several MIt sessions to maximise performance gains, but they do not support the additional effects of a-tDCS.

Medication exposure of the dyad patient-caregiver in Alzheimer's disease and related dementias: a cross-sectional study.

BACKGROUND: Patients with Alzheimer's disease and related dementias and their caregivers can be defined as people with higher risk of developing medication-related problems due to aging and polypharmacy. AIM: To assess the medication exposure of patient with Alzheimer's disease and related dementias and their caregivers. METHOD: Ancillary cross-sectional study based on baseline medication data of the PHARMAID RCT. The PHARMAID study was a multi-center RCT assessing an integrated pharmaceutical care at a psychosocial program. Older outpatients with Alzheimer's disease and related dementias and their older caregivers were eligible for inclusion. Baseline medication data were used to assess the medication exposure, illustrated by the number of medications, the prevalence of potentially inappropriate medications (PIMs) using the EU(7)-PIM list and the Medication Regimen Complexity Index (MRCI). RESULTS: Seventy-three dyads were included in this ancillary study. The mean numbers (SD) of medications used by patients was 6.8 (2.6) and by caregivers was 4.7 (3.7). Overall, 60.3% of patients used at least one PIM and 47.9% of caregivers. Regarding the medication regimen complexity, the mean MRCI was 16.3(8.1) for patients and 11.3(10.5) for caregivers. CONCLUSION: The results of this study confirm the relevance of carrying out medication review with patients, but also with their caregivers who can be considered as hidden patients.

Dementia and comorbidities in primary care: a scoping review.

BACKGROUND: People with dementia (PwD) are known to have more chronic conditions compared to those without dementia, which can impact the clinical presentation of dementia, complicate clinical management and reduce overall quality of life. While primary care providers (PCPs) are integral to dementia care, it is currently unclear how PCPs adapt dementia care practices to account for comorbidities. This scoping review maps recent literature that describes the role for PCPs in the prevention, detection/diagnosis and management of dementia in the context of comorbidities, identifies critical knowledge gaps and proposes potential avenues for future research. METHODS: We searched for peer-reviewed literature published between 2017-2022 in MEDLINE, Cochrane Library, and Scopus using key terms related to dementia, primary care, and comorbidity. The literature was screened for relevance by title-abstract screening and subsequent full-text screening. The prioritized papers were categorized as either 'Risk Assessment and Prevention', 'Screening, Detection, and Diagnosis' or 'Management' and were further labelled as either 'Tools and Technologies', 'Recommendations for Clinical Practice' or 'Programs and Initiatives'. RESULTS: We identified 1,058 unique records in our search and respectively excluded 800 and 230 publications during title-abstract and full-text screening. Twenty-eight articles were included in our review, where ~ 50% describe the development and testing of tools and technologies that use pre-existing conditions to assess dementia risk. Only one publication provides official dementia screening guidelines for PCPs in people with pre-existing conditions. About 30% of the articles discuss managing the care of PwD, where most were anchored around models of multidisciplinary care and mitigating potentially inappropriate prescribing. CONCLUSION: To our knowledge, this is the first scoping review that examines the role for PCPs in the prevention, detection/diagnosis and management of dementia in the context of comorbidities. Given our findings, we recommend that future studies: 1) further validate tools for risk assessment, timely detection and diagnosis that incorporate other health conditions; 2) provide additional guidance into how comorbidities could impact dementia care (including prescribing medication) in primary care settings; 3) incorporate comorbidities into primary care quality indicators for dementia; and 4) explore how to best incorporate dementia and comorbidities into models/frameworks of holistic, person-centred care.

Impact of pharmaceutical care integrated at a psychosocial intervention to reduce caregiver's burden in Alzheimer's disease or related dementias: Negative results at 18 months and difficulties to conduct PHARMAID RCT.

Background: Psychosocial interventions for caregivers of patients with Alzheimer disease and relative dementias (ADRD) reported a caregiver burden improvement. Multicomponent intervention integrating pharmaceutical care has not yet been evaluated while ADRD patients and their caregivers are exposed to high risk of drug-related problems. The PHARMAID study aimed to assess the impact of personalized pharmaceutical care integrated to a psychosocial program on the burden of ADRD caregivers at 18 months. Methods: The PHARMAID RCT was conducted between September 2016 and June 2020 [ClinicalTrials.gov: NCT02802371]. PHARMAID study planned to enroll 240 dyads, i.e. ADRD patients and caregivers, whose inclusion criteria were: outpatient with mild or major neurocognitive disorders due to ADRD, living at home, receiving support from a family caregiver. Three parallel groups compared a control group with two interventional groups: psychosocial intervention and integrated pharmaceutical care at a psychosocial intervention. The main outcome was the caregiver burden assessed by the Zarit Burden Index (ZBI, score range 0-88) at 18 months. Results: Overall, 77 dyads were included (32% of the expected sample size). At 18 months, the mean ZBI scores were 36.7 ± 16.8 in the control group, 30.3 ± 16.3 for the group with psychosocial intervention, and 28.8 ± 14.1 in group with integrated pharmaceutical care at psychosocial intervention. No significant difference was demonstrated between the three groups (p = 0.326). Conclusions: The findings suggest that PHARMAID program had no significant impact on caregiver burden at 18 months. Several limitations have been highlighted and discussed by the authors in order to formulate recommendations for further research.

Empowering general practitioners in dementia care: The ANTISTIGMA education intervention in Europe.

BACKGROUND: There is a well-documented lack or delay of diagnosis of dementia in all countries, including in Europe. Most general practitioners (GPs) have acquired adequate academic and scientific information about dementia but avoid using it in practice because of stigma. OBJECTIVES: To persuade GPs of their role in dementia detection, an Antistigma education intervention was designed, with teaching objectives focusing on "Why" and "How" to diagnosis and manage dementia, based on ethical and practical content, as opposed to classical training centered on teaching "What", with mainly academic content. METHODS: During the European Joint Action "ACT ON DEMENTIA", the Antistigma education intervention was implemented in four Universities: Lyon and Limoges (France), Sofia (Bulgaria) and Lublin (Poland). General data, including information about training and experience in dementia, was collected. Specific scales measured Dementia Negative Stereotypes DNS and Dementia Clinical Confidence D-CO before and after training. RESULTS: 134 GPs and 58 residents R completed the training. The participants were mainly women (74%), and the mean age was 42.8 ± 13.2. Before training, participants expressed difficulties in defining GPs role and worries about inflicting Stigma, Risks of diagnosis, Lack of benefit and Communication difficulties. Participants' D-CO was significantly higher for Diagnosis process (64%) than for other clinical situations. After training, total NS was reduced from 34.2% to 29.9% (p < 0.001), and stereotypes were improved: GPs' role (40.1% reduced to 35.9%; p < 0.001), Stigma (38.7% reduced to 35.5%; p < 0.001), Risks of diagnosis (39.0% reduced to 33.3%; p < 0.001), Lack of Benefit (29.3% reduced to 24.6%; p < 0.001) and Communication difficulties (19.9% reduced to 16.9%; p < 0.001). After training, D-CO was significantly increased in all the clinical situations (p < 0.001), but stayed highest for Diagnosis Process. There was no significant difference between the universities. Participants who benefited best from the Antistigma education intervention were those without training in Geriatrics and those working in nursing homes (who reduced the most D-NS), as well younger participants and those who managed less than five people living with dementia per week (who increased the most D-CO). CONCLUSION: The Antistigma program is based on the idea that most often GPs and R have acquired adequate academic and scientific information about dementia but avoid using it in practice because of stigma. These results outline the importance of addressing ethical issues and practical management situations in dementia education, to empower GPs in dementia care.

[Early management of presbycusis: recommendations from the French Society of Otorhinolaryngology and Head and Neck Surgery, the French Society of Audiology, and the French Society of Geriatrics and Gerontology]. / Recommandations de la Société française d'otorhinolaryngologie et de chirurgie de la face et du cou, la Société française d'audiologie et la Société française de gériatrie et gérontologie pour la prise en charge précoce de la presbyacousie.

INTRODUCTION: Presbycusis is the physiological decrease in hearing due to advancing age and begins well before the sixth decade. These recommendations recall the principles of early diagnosis of presbycusis and the means of optimal rehabilitation as soon as the first symptoms appear. MATERIAL AND METHODS: The recommendations are based on a systematic analysis of the literature carried out by a multidisciplinary group of doctors and audioprosthetists from all over France. They are graded A, B, C or expert opinion according to decreasing level of scientific evidence. RESULTS: The diagnosis of presbycusis is more difficult at the beginning of its evolution but a certain number of tools are available for its early diagnosis and its management in face-to-face or even distance learning. CONCLUSION: In case of a clinical profile suggestive of presbycusis in a young subject, especially if there are several family cases, it is recommended to propose a genetic investigation. It is recommended to perform free-field speech audiometry in noise to measure intelligibility in an environment as close as possible to reality. Questionnaires can be used in addition to audiometry to best assess the patient's disability. It is recommended that hearing rehabilitation with a hearing aid or cochlear implant may slow or prevent cognitive decline. Combined auditory and cognitive rehabilitation should be offered regardless of the time elapsed since the fitting. It is recommended to integrate programs accessible via smartphones, tablets or the Internet, integrating different training domains in addition to face-to-face sessions.

White matter hyperintensities in Alzheimer's disease: Beyond vascular contribution.

White matter hyperintensities (WMH), frequently seen in older adults, are usually considered vascular lesions, and participate in the vascular contribution to cognitive impairment and dementia. However, emerging evidence highlights the heterogeneity of WMH pathophysiology, suggesting that non-vascular mechanisms could also be involved, notably in Alzheimer's disease (AD). This led to the alternative hypothesis that in AD, part of WMH may be secondary to AD-related processes. The current perspective brings together the arguments from different fields of research, including neuropathology, neuroimaging and fluid biomarkers, and genetics, in favor of this alternative hypothesis. Possible underlying mechanisms leading to AD-related WMH, such as AD-related neurodegeneration or neuroinflammation, are discussed, as well as implications for diagnostic criteria and management of AD. We finally discuss ways to test this hypothesis and remaining challenges. Acknowledging the heterogeneity of WMH and the existence of AD-related WMH may improve personalized diagnosis and care of patients.

Potentially inappropriate medications and anticholinergic and sedative burden in older community-dwelling patients with advanced chronic kidney disease

Objective: Regarding older patients, multiple chronic conditions lead to the intake of multiple medications, involving a higher risk of adverse drug events. In older patients with advanced chronic kidney disease, the medication exposure was poorly explored. The aim of this study was to describe the use of potentially inappropriate medications and medications with anticholinergic and sedative properties in older community-dwelling patients with advanced chronic kidney disease. Methods: An observational study was conducted in a geriatric day-care unit. All patients aged over 65 years with advanced chronic kidney disease, defined by estimated glomerular filtration rate < 20 mL/min/1.73 m2 or estimated glomerular filtration rate > 20 mL/min/1.73 m2 with rapid progression, and referred by nephrologist for pretransplant comprehensive geriatric assessment, were included in the study. Potentially inappropriate medications were identified using the EU(7)-PIM list, and he anticholinergic and sedative drug exposure was measured using the Drug Burden Index. Results: Overall, 139 patients were included in the study (mean age 74.4 ± 3.3 years, 32.4% females, 61.9% on dialysis). Potentially inappropriate medications were used by 74.1% (103/139) of patients and were mainly represented by proton pump inhibitors, alpha-1-blockers and central antihypertensive drugs. Regarding anticholinergic and / or sedative medications, 79.9% (111/139) of older patients were exposed. Conclusion: In older community-dwelling patients with advanced chronic kidney disease, the prevalence of potentially inappropriate medication exposure and anticholinergic and sedative exposure was high. Interventions focusing on deprescription of these inappropriate medications should be conducted in this specific population.

Objectif: Chez le patient âgé, la polypathologie est souvent associée à la prise de plusieurs médicaments, impliquant un risque élevé d'iatrogénie médicamenteuse. L'exposition médicamenteuse a été peu explorée chez les patients âgés atteints d'insuffisance rénale chronique. L'objectif de cette étude est de décrire l'exposition aux médicaments potentiellement inappropriés et aux médicaments présentant des propriétés anticholinergiques et sédatives chez ces patients. Méthodes: Il s'agit d'une étude observationnelle conduite au sein d'un hôpital de jour gériatrique. Tous les patients âgés de plus de 65 ans avec une maladie rénale chronique avancée, définie par un débit de filtration glomérulaire estimé inférieur à 20 mL/min/1,73 m² ou supérieur à 20 mL/min/1,73 m² avec une progression rapide, et adressés par un néphrologue pour la réalisation d'une évaluation gériatrique standardisée pré-transplantation rénale, ont été inclus dans l'étude. Les médicaments potentiellement inappropriés ont été identifiés à partir de la liste EU(7)-PIM, et l'exposition aux médicaments anticholinergiques et sédatifs a été mesurée à partir du Drug Burden Index. Résultats: Un total de 139 patients a été inclus dans l'étude (74,4 ± 3,3 ans, 32,4 % de femmes, 61,9 % dialysés). Des médicaments potentiellement inappropriés ont été retrouvés chez 74,1 % (103/139) des patients. Ils étaient principalement représentés par les inhibiteurs de la pompe à protons, les alpha-1-bloquants et les antihypertenseurs centraux. Concernant les médicaments anticholinergiques et/ou sédatifs, 79,9 % (111/139) des patients âgés étaient exposés. Conclusion: L'étude montre que la prévalence de l'exposition aux médicaments potentiellement inappropriés et aux médicaments anticholinergiques et/ou sédatifs est élevée chez les patients âgés atteints de maladie rénale chronique avancée. Des interventions portant sur la déprescription de ces médicaments devraient être menées auprès de cette population spécifique.

Educational care for patients with Alzheimer's disease and their caregivers in France: A mapping proposal.

OBJECTIVES: To formalize a proposal for educational approach for patients with Alzheimer's disease and related dementias (ADRD) and caregivers across existing diagnosis/care organizations and structures. METHODS: Three steps:1/ identifying the existing organizations and structures that could be involved in educational care; 2/ identifying the main educational skills of interest for ADRD patients and caregivers; 3/ conducting a survey among these organizations and structures to achieve a mapping proposal of educational care. RESULTS: Nine organizations and structures, and 29 educational skills of interest were identified for the step 3 survey. Overall, 423 organizations/structures completed the step 3 survey. Twelve of 29 educational skills were covered by 50% of organizations/structures included. The most covered skills were "Maintaining autonomy in daily living activities", "coping with cognitive disorders", and "coping with behavioral disorders". CONCLUSIONS: A mapping of educational care that could be provided by the different structures and organizations involved in the ADRD care pathway was proposed regarding their missions and intervention place. PRACTICE IMPLICATIONS: Policy makers and funding bodies will need to invest in the healthcare professionals' training about educational approach and ADRD in order to extend educational care throughout the patient's care pathway.

Global estimates on the number of persons across the Alzheimer's disease continuum.

INTRODUCTION: Global estimates on numbers of persons in early stages of Alzheimer's disease (AD), including prodromal and preclinical, are lacking, yet are needed to inform policy decisions on preventive measures and planning for future therapies targeting AD pathology. METHODS: We synthesized the literature on prevalence across the AD continuum and derived a model estimating the number of persons, stratified by 5-year age groups, sex, and disease stage (AD dementia, prodromal AD, and preclinical AD). RESULTS: The global number of persons with AD dementia, prodromal AD, and preclinical AD were estimated at 32, 69, and 315 million, respectively. Together they constituted 416 million across the AD continuum, or 22% of all persons aged 50 and above. DISCUSSION: Considering predementia stages, the number of persons with AD is much larger than conveyed in available literature. Our estimates are uncertain, especially for predementia stages in low- and middle-income regions where biomarker studies are missing.

Associations among hypertension, dementia biomarkers, and cognition: The MEMENTO cohort.

INTRODUCTION: Approximately 40% of dementia cases could be delayed or prevented acting on modifiable risk factors including hypertension. However, the mechanisms underlying the hypertension-dementia association are still poorly understood. METHODS: We conducted a cross-sectional analysis in 2048 patients from the MEMENTO cohort, a French multicenter clinic-based study of outpatients with either isolated cognitive complaints or mild cognitive impairment. Exposure to hypertension was defined as a combination of high blood pressure (BP) status and antihypertensive treatment intake. Pathway associations were examined through structural equation modeling integrating extensive collection of neuroimaging biomarkers and clinical data. RESULTS: Participants treated with high BP had significantly lower cognition compared to the others. This association was mediated by higher neurodegeneration and higher white matter hyperintensities load but not by Alzheimer's disease (AD) biomarkers. DISCUSSION: These results highlight the importance of controlling hypertension for prevention of cognitive decline and offer new insights on mechanisms underlying the hypertension-dementia association. HIGHLIGHTS: Paths of hypertension-cognition association were assessed by structural equation models. The hypertension-cognition association is not mediated by Alzheimer's disease biomarkers. The hypertension-cognition association is mediated by neurodegeneration and leukoaraiosis. Lower cognition was limited to participants treated with uncontrolled blood pressure. Blood pressure control could contribute to promote healthier brain aging.

Validity and Performance of Blood Biomarkers for Alzheimer Disease to Predict Dementia Risk in a Large Clinic-Based Cohort.

BACKGROUND AND OBJECTIVE: Blood biomarkers for Alzheimer disease (AD) have consistently proven to be associated with CSF or PET biomarkers and effectively discriminate AD from other neurodegenerative diseases. Our aim was to test their utility in clinical practice, from a multicentric unselected prospective cohort where patients presented with a large spectrum of cognitive deficits or complaints. METHODS: The MEMENTO cohort enrolled 2,323 outpatients with subjective cognitive complaint (SCC) or mild cognitive impairment (MCI) consulting in 26 French memory clinics. Participants had neuropsychological assessments, MRI, and blood sampling at baseline. CSF sampling and amyloid PET were optional. Baseline blood Aß42/40 ratio, total tau, p181-tau, and neurofilament light chain (NfL) were measured using a Simoa HD-X analyzer. An expert committee validated incident dementia cases during a 5-year follow-up period. RESULTS: Overall, 2,277 individuals had at least 1 baseline blood biomarker available (n = 357 for CSF subsample, n = 649 for PET subsample), among whom 257 were diagnosed with clinical AD/mixed dementia during follow-up. All blood biomarkers but total tau were mildly correlated with their equivalence in the CSF (r = 0.33 to 0.46, p < 0.0001) and were associated with amyloid-PET status (p < 0.0001). Blood p181-tau was the best blood biomarker to identify amyloid-PET positivity (area under the curve = 0.74 [95% CI = 0.69; 0.79]). Higher blood and CSF p181-tau and NfL concentrations were associated with accelerated time to AD dementia onset with similar incidence rates, whereas blood Aß42/40 was less efficient than CSF Aß42/40. Blood p181-tau alone was the best blood predictor of 5-year AD/mixed dementia risk (c-index = 0.73 [95% CI = 0.69; 0.77]); its accuracy was higher in patients with clinical dementia rating (CDR) = 0 (c-index = 0.83 [95% CI = 0.69; 0.97]) than in patients with CDR = 0.5 (c-index = 0.70 [95% CI = 0.66; 0.74]). A "clinical" reference model (combining demographics and neuropsychological assessment) predicted AD/mixed dementia risk with a c-index = 0.88 [95% CI = 0.86-0.91] and performance increased to 0.90 [95% CI = 0.88; 0.92] when adding blood p181-tau + Aß42/40. A "research" reference model (clinical model + apolipoprotein E genotype and AD signature on MRI) had a c-index = 0.91 [95% CI = 0.89-0.93] increasing to 0.92 [95% CI = 0.90; 0.93] when adding blood p181-tau + Aß42/40. Chronic kidney disease and vascular comorbidities did not affect predictive performances. DISCUSSION: In a clinic-based cohort of patients with SCC or MCI, blood biomarkers may be good hallmarks of underlying pathology but add little to 5-year dementia risk prediction models including traditional predictors.

Effect of reduction in brain amyloid levels on change in cognitive and functional decline in randomized clinical trials: An instrumental variable meta-analysis.

INTRODUCTION: Whether the reduction in brain amyloid beta (Aß) plaque alone may substantially slow cognitive and functional decline in patients with dementia or mild cognitive impairment due to Alzheimer's disease (AD) remains debated. METHODS: An instrumental variable meta-analysis was performed to infer the effect of change in positron emission tomography (PET)-measured Aß standardized uptake value ratio (SUVR) on cognitive and functional decline. RESULTS: Pooling data from 16 randomized trials demonstrates that each 0.1-unit decrease in PET Aß SUVR is associated with a reduction (95% confidence interval) by 0.09 (0.034-0.15), 0.33 (0.12-0.55), and 0.13 (0.017-0.24) point in the average change of the Clinical Dementia Rating-Sum of Boxes, the Alzheimer's Disease Assessment Scale-Cognitive Subscale, and the Mini-Mental State Examination, respectively. DISCUSSION: This meta-analysis provides statistically significant evidence of a likely causal relationship between a reduction in Aß plaque and a reduction in cognitive and functional decline in patients with AD. HIGHLIGHTS: A widely cited meta-analysis article concluded amyloid beta reduction does not substantially improve cognition. We identified data inconsistencies in the initial publication and found new trial data. We repeated the meta-analysis after correcting data inconsistencies and adding new trial data. Updated results suggested statistically significant clinical benefit of amyloid beta reduction. Amyloid beta is a viable biological target for the treatment and prevention of AD.

[Impact of animal-assisted therapy on well-being in patients with Alzheimer's disease (ELIAUT study)]. / Impact de la thérapie assistée par l'animal sur le bien être chez des patients présentant une maladie d'Alzheimer (étude ELIAUT).

The development of non-pharmacological interventions, including animal-assisted therapy (AAT), is an encouraging method for the care of people with Alzheimer's disease (AD). A single-center, randomized, single-blind, controlled intervention study was proposed to compare immediate well-being measured by a visual analog scale (EVIBE) as primary outcome between the intervention group (AAT combined with cognitive stimulation) and the control group (cognitive stimulation only) in AD patients. Secondary outcomes were explored, such as well-being after intervention (also with the EVIBE), cognitive performance (measured by Alzheimer's Disease Assessment Scale, cognitive part GRECO version), behavioral and psychological symptoms of dementia (with the Neuropsychiatric Inventory Behavioral Scale-Nursing Home Version), current depressive symptomatology (with the 30 items Geriatric Depression Scale [GDS 30]) and anxiety (by the State-Trait Anxiety Inventory). Forty-two patients were included, 22 in the intervention group and 20 in the control group. The mean age was 82.5 years and mean MMSE score 19.2 in the control group and 81.4 years and mean MMSE score 18.4 in the TAA group. The results show a significant effect of the intervention on well-being after four weeks (p = 0.048), but no significant effect on cognitive functioning, behavioral and psychological symptoms of dementia. This study shows a small effect of TAA on well-being four weeks after the end of the intervention. The assessment of well-being by another measurement tool and the collection of observations made by the care team could be explored in future studies, which could require a larger sample and a longer follow-up.

Anodal tDCS does not enhance the learning of the sequential finger-tapping task by motor imagery practice in healthy older adults.

Background: Motor imagery practice (MIP) and anodal transcranial direct current stimulation (a-tDCS) are innovative methods with independent positive influence on motor sequence learning (MSL) in older adults. Objective: The present study investigated the effect of MIP combined with a-tDCS over the primary motor cortex (M1) on the learning of a finger tapping sequence of the non-dominant hand in healthy older adults. Methods: Thirty participants participated in this double-blind sham-controlled study. They performed three MIP sessions, one session per day over three consecutive days and a retention test 1 week after the last training session. During training / MIP, participants had to mentally rehearse an 8-element finger tapping sequence with their left hand, concomitantly to either real (a-tDCS group) or sham stimulation (sham-tDCS group). Before and after MIP, as well as during the retention test, participants had to physically perform the same sequence as fast and accurately as possible. Results: Our main results showed that both groups (i) improved their performance during the first two training sessions, reflecting acquisition/on-line performance gains, (ii) stabilized their performance from one training day to another, reflecting off-line consolidation; as well as after 7 days without practice, reflecting retention, (iii) for all stages of MSL, there was no significant difference between the sham-tDCS and a-tDCS groups. Conclusion: This study highlights the usefulness of MIP in motor sequence learning for older adults. However, 1.5 mA a-tDCS did not enhance the beneficial effects of MIP, which adds to the inconsistency of results found in tDCS studies. Future work is needed to further explore the best conditions of use of tDCS to improve motor sequence learning with MIP.

Impaired Facial Emotion Recognition and Gaze Direction Detection in Mild Alzheimer's Disease: Results from the PACO Study.

BACKGROUND: Facial emotion recognition (FER) and gaze direction (GD) identification are core components of social cognition, possibly impaired in many psychiatric or neurological conditions. Regarding Alzheimer's disease (AD), current knowledge is controversial. OBJECTIVE: The aim of this study was to explore FER and GD identification in mild AD compared to healthy controls. METHODS: 180 participants with mild AD drawn from the PACO study and 74 healthy elderly controls were enrolled. Participants were asked to complete three socio-cognitive tasks: face sex identification, recognition of facial emotions (fear, happiness, anger, disgust) expressed at different intensities, and GD discrimination. Multivariate analyses were conducted to compare AD participants and healthy controls. RESULTS: Sex recognition was preserved. GD determination for subtle deviations was impaired in AD. Recognition of prototypically expressed facial emotions was preserved while recognition of degraded facial emotions was impacted in AD participants compared to controls. Use of multivariate analysis suggested significant alteration of low-expressed fear and disgust recognition in the AD group. CONCLUSION: Our results showed emotion recognition and GD identification in patients with early-stage AD compared to elderly controls. These impairments could be the object of specific therapeutic interventions such as social cognition remediation or raising awareness of primary caregivers to improve the quality of life of patients with early AD.

Practical management of frailty in older patients with heart failure: Statement from a panel of multidisciplinary experts on behalf the Heart Failure Working Group of the French Society of Cardiology and on behalf French Society of Geriatrics and Gerontology.

AIMS: The heart failure (HF) prognosis in older patients remains poor with a high 5-years mortality rate more frequently attributed to noncardiovascular causes. The complex interplay between frailty and heart failure contribute to poor health outcomes of older adults with HF independently of ejection fraction. The aim of this position paper is to propose a practical management of frailty in older patients with heart failure. METHODS: A panel of multidisciplinary experts on behalf the Heart Failure Working Group of the French Society of Cardiology and on behalf French Society of Geriatrics and Gerontology conducted a systematic literature search on the interlink between frailty and HF, met to propose an early frailty screening by non-geriatricians and to propose ways to implement management plan of frailty. Statements were agreed by expert consensus. RESULTS: Clinically relevant aspects of interlink between frailty and HF have been reported to identify the population eligible for screening and the most suitable screening test(s). The frailty screening program proposed focuses on frailty model defined by an accumulation of deficits including geriatric syndromes, comorbidities, for older patients with HF in different settings of care. The management plan of frailty includes optimization of HF pharmacological treatments and non-surgical device treatment as well as optimization of a global patient-centred biopsychosocial blended collaborative care pathway. CONCLUSION: The current manuscript provides practical recommendations on how to screen and optimize frailty management in older patients with heart failure.