J Am Med Dir Assoc

OBJECTIVES: Identifying risk factors for falls can improve outcomes in older patients without cognitive decline. Yet this has not been demonstrated in older people with mild cognitive impairment (MCI). We therefore sought to better identify risk factors for falls in this particular group. DESIGN: The analysis was conducted on the MEMENTO cohort, which is a large, French, prospective cohort. SETTING AND PARTICIPANTS: We included older people (>65 years old) with MCI (defined from neuropsychological scores) and a Short Physical Performance Battery (SPPB) score at baseline. METHODS: Fallers were defined as participants having fallen at least once during the study's 2-year follow-up period. We compared clinical, neuropsychological, and biological data at baseline in fallers vs nonfallers. Additional analyses were performed on the following subgroups: women, men, people aged ≥75 years. RESULTS: Of the 1416 people included in our study, 194 (13.5%) fell at least once. A bivariate analysis showed that fallers were older, predominantly women, less independent in activities of daily living, and more apathetic. Fallers performed less well in executive function, balance, and gait tests. In a multivariable analysis, only age, gender, the number of limitations in instrumental activities of daily living, and living alone were significantly associated with falls. In a multivariable analysis of the subgroup of oldest patients and of the subgroup of men, executive function was significantly worse in fallers than in nonfallers. CONCLUSION AND IMPLICATIONS: Our results demonstrate that easily attainable risk factors can be used to identify individuals with MCI with a higher risk of falls and for whom prevention could be beneficial. Future studies are needed to further evaluate the role of mild executive dysfunction in certain subgroups, such as men and oldest patients

A phase III randomized multicenter trial evaluating cognition in post-menopausal breast cancer patients receiving adjuvant hormonotherapy

International audienc

Twenty‐year trends in patient referrals throughout the creation and development of a regional memory clinic network

Introduction: Memory clinics (MCs) are the main model for dementia diagnosis and care. Following the development of a MC network in Northern France, our objectives were to assess its impact on patient characteristics over 20 years.Methods: The characteristics of new consultants were studied from 1997 to 2016.Results: New consultants increased from 774 per year in 1997 to 26258 per year in 2016, as the number of MCs increased from 12 to 29. Over time, patients were progressively older and less educated, and more were living alone. A greater proportion of patients were referred by specialists. Referral delay and home-to-MC distance kept decreasing. The oldest patients were referred at a progressively less-severe stage. The proportion of young patients kept increasing in the tertiary referral center.Discussions: The development of a region-wide MC network led to increased referral of vulnerable patients and differentiation of the tertiary referral center over time

Prévention des mécanismes de nucléation et propagation de tau par immunothérapie anti-tau ciblant un épitope central

Marie Albert, Georges Mairet-Coello, Luc Buée and Morvane Colin : these author contributed equally to this work.International audienceTauopathies are neurodegenerative diseases characterized by the intraneuronal accumulation of aggregated tau. The staging of this neurodegenerative process is well established for Alzheimer's disease as well as for other tauopathies. The stereotypical pattern of tau pathology in these diseases is consistent with the hypothesis that the tau protein can spread in a 'prion-like' manner. It proposes that extracellular pathological tau species can transmit pathology from cell to cell. Accordingly, by targeting these spreading species with therapeutic antibodies one should be able to slow or halt the progression of tau pathology. To be effective, antibodies should neutralize the pathological species present in Alzheimer's disease brains and block their cell-to-cell spread. To evaluate both aspects, tau antibody D, which recognizes an epitope in the central region of tau, and was selected for its outstanding ability to block tau seeding in cell based assays, was used in this study. Here, we addressed two fundamental questions: (i) can this anti-tau antibody neutralize the pathological species present in Alzheimer's disease brains; and (ii) can it block the cell-to-cell spread of tau seeds in vivo? First, antibody D effectively prevented the induction of tau pathology in the brains of transgenic mice that had been injected with human Alzheimer's disease brain extracts, showing that it could effectively neutralize the pathological species present in these extracts. Second, by using K18 P301L tau fibrils to induce pathology, we further demonstrated that antibody D was also capable of blocking the progression of tau pathology to distal brain regions. In contrast, an amino-terminal tau antibody, which was less effective at blocking tau seeding in vitro showed less efficacy in reducing Alzheimer's disease patient tau driven pathology in the transgenic mouse model. We did not address whether the same is true for a spectrum of other amino-terminal antibodies that were tested in vitro. These data highlight important differences between tau antibodies and, when taken together with other recently published data, suggest that epitope may be important for function

Characteristics and progression of patients with frontotemporal dementia in a regional memory clinic network

International audienceBackground: Due to heterogeneous clinical presentation, difficult differential diagnosis with Alzheimer’s disease (AD) and psychiatric disorders, and evolving clinical criteria, the epidemiology and natural history of frontotemporal lobar degeneration (FTD) remain elusive. In order to better characterize FTD patients, we relied on the database of a regional memory clinic network with standardized diagnostic procedures and chose AD patients as a comparator.Methods: Patients that were first referred to our network between January 2010 and December 2016 and whose last clinical diagnosis was degenerative or vascular dementia were included. Comparisons were conducted between FTD and AD as well as between the different FTD syndromes, divided into language variants (lvFTD), behavioral variant (bvFTD), and FTD with primarily motor symptoms (mFTD). Cognitive progression was estimated with the yearly decline in Mini Mental State Examination (MMSE).Results: Among the patients that were referred to our network in the 6-year time span, 690 were ultimately diagnosed with FTD and 18,831 with AD. Patients with FTD syndromes represented 2.6% of all-cause dementias. The age-standardized incidence was 2.90 per 100,000 person-year and incidence peaked between 75 and 79 years. Compared to AD, patients with FTD syndromes had a longer referral delay and delay to diagnosis. Patients with FTD syndromes had a higher MMSE score than AD at first referral while their progression was similar. mFTD patients had the shortest survival while survival in bvFTD, lvFTD, and AD did not significantly differ. FTD patients, especially those with the behavioral variant, received more antidepressants, anxiolytics, and antipsychotics than AD patients.Conclusions: FTD syndromes differ with AD in characteristics at baseline, progression rate, and treatment. Despite a broad use of the new diagnostic criteria in an organized memory clinic network, FTD syndromes are longer to diagnose and account for a low proportion of dementia cases, suggesting persistent underdiagnosis. Congruent with recent publications, the late peak of incidence warns against considering FTD as being exclusively a young-onset dementia