Potential efficacy of T and B lymphocyte-targeted therapies on articular involvement of patients with rheumatoid arthritis and systemic sclerosis overlap syndrome. Results from a 2-centre series of 22 cases.

OBJECTIVES: To analyse in routine practice the efficacy of targeted therapies on joint involvement of patients with rheumatoid arthritis/systemic sclerosis (RA/SSc) overlap syndrome. METHODS: This was a retrospective analysis of medical records of two academic centres over a 10-year period. Joint response to targeted therapies was measured according to EULAR criteria based on Disease Activity Score (DAS)-28. In addition, changes in CRP level and glucocorticoid consumption were recorded. RESULTS: Nineteen patients were included. Methotrexate (n=11) and hydroxychloroquine (n=4) were the most used first-line treatments. Targeted therapies were frequently used (n=14). Tocilizumab was the most selected therapy (n=8), then rituximab (n=5), abatacept and anti-tumour necrosis factor (n=4). Twenty-one treatment sequences were assessed, including 18 with EULAR response criteria. Responses were "good" or "moderate" in 100% (4/4) of patients treated with abatacept, 80% (4/5) with rituximab, 40% (2/5) with tocilizumab, and 25% (1/4) with anti-TNF. T and B lymphocyte-targeted therapies (abatacept, rituximab) resulted more frequently in a "good" or "moderate" response compared to cytokine inhibitors (tocilizumab, etanercept, infliximab) with a significant decrease in DAS-28 at 6 months (-1.75; p=0.016) and a trend to a lower consumption of glucocorticoids. CCONCLUSIONS: In patients with RA/SSc overlap syndrome refractory to conventional synthetic-DMARDs, T and B lymphocyte-targeted therapies seem to be a promising therapeutic option to control joint activity.

Bone, cognitive, and anthropometric profiles and their relation to fracture sites in fallers: a cross-sectional study.

Risk factors involved in the different osteoporotic fracture locations are not well-known. The results of this study suggest that there is not one typical profile characterising a particular fracture site but that the occurrence of a fracture may result from the combination of different bone, cognitive, and anthropometrics characteristics. PURPOSE: Risk factors involved in the different osteoporotic fracture locations are not well-known. The aim of this study was to identify the differences in bone, cognitive, and anthropometric characteristics between different fracture sites, and to determine whether the site of a fall-related fracture is related to a specific profile. METHODS: One hundred six women aged 55 years and older with a recent fall-related fracture of the hip (n = 30), humerus (n = 28), wrist (n = 32), or ankle (n = 16) were included. Bone, cognitive, and anthropometric characteristics were first compared among the four fracture site groups. Then, a principal component analysis (PCA) was performed and a comparison was made between the four profiles identified by the first two PCA components. RESULTS: The four fracture site groups differed significantly in their education level, bone mineral density (BMD), body mass index (BMI), fear of falling, and number of errors in the Trail Making Test B, an executive function test. Each of the four fracture sites was found in each four PCA profiles, albeit with a different distribution. The profiles differed mainly by bone, cognitive, and anthropometric characteristics, but also by fear of falling. CONCLUSIONS: The fall-related fracture sites differ significantly in anthropometric and bone parameters, in fear of falling and in cognitive abilities. There is not one typical bone, cognitive, and anthropometric profile characterising a particular fall-related site, but rather several possible profiles for a given site. This suggests that the fracture site depends on a combination of several characteristics of the patient.

Clinical and ultrasonographic evaluation of the window of opportunity for retreatment with rituximab in rheumatoid arthritis patients from a multicentre real-life study.

OBJECTIVES: To determine a potential window of opportunity for retreatment with rituximab in patients with rheumatoid arthritis (RA) from a multicentre longitudinal real-life study based on tight monitoring with ultrasonography (US). METHODS: Thirty RA patients treated with rituximab were included. US parameters were collected at each time (8 visits) of the 18-month follow-up, notably the global score of power Doppler (PD) activity. Clinical relapse was defined as a DAS28 ESR of >3.2 after 6 months in responders while US relapse was defined as an increase of ≥20% of the global score of PD activity. The decision of retreatment was based exclusively on clinical findings. RESULTS: A total of 29 patients were analysed (mean (SD) age: 57.2 (12.2) years; female gender: 66%). The mean (SD) PD score decreased from 8.8 (5.2) at baseline to 4.9 (4.3) at 6 months (p <0.0001). A clinical response was observed at Month 4 or Month 6 for 93% of patients. A total of 19 patients had a first clinical relapse (with or without US relapse) after Month 6 (18 of them were retreated with rituximab). Among 10 patients without clinical relapse, 3 had US relapse (only one was retreated) and 7 had no US relapse (but 4 were retreated). CONCLUSIONS: This study highlights a great heterogeneity in terms of sequence of clinical relapse, US relapse and retreatment in RA patients receiving rituximab. Therefore, US monitoring does not seem to be relevant to determine the best time for retreatment with rituximab.

The diagnostic challenge of patients with anti-U1-RNP antibodies.

Anti-U1-RNP antibodies are necessary for the diagnosis of mixed connective tissue disease (MCTD), but they are also prevalent in other connective tissue diseases, especially systemic lupus erythematosus (SLE), from which distinction remains challenging. We aimed to describe the presentation and outcome of patients with anti-U1-RNP antibodies and to identify factors to distinguish MCTD from SLE. We retrospectively applied the criteria sets for MCTD, SLE, systemic sclerosis (SSc) and rheumatoid arthritis (RA) to all patients displaying anti-U1-RNP antibodies in the hospital of Caen from 2000 to 2020. Thirty-six patients were included in the analysis. Eighteen patients (50%) satisfied at least one of the MCTD classifications, 11 of whom (61%) also met 2019 ACR/EULAR criteria for SLE. Twelve other patients only met SLE without MCTD criteria, and a total of 23 patients (64%) met SLE criteria. The most frequent manifestations included Raynaud's phenomenon (RP, 91%) and arthralgia (67%). We compared the characteristics of patients meeting only the MCTD (n = 7), SLE (n = 12), or both (n = 11) criteria. Patients meeting the MCTD criteria were more likely to display SSc features, including sclerodactyly (p < 0.01), swollen hands (p < 0.01), RP (p = 0.04) and esophageal reflux (p < 0.01). The presence of scleroderma features (swollen hands, sclerodactyly, gastro-oesophageal reflux), was significantly associated with the diagnosis of MCTD. Conversely, the absence of those manifestations suggested the diagnosis of another definite connective tissue disease, especially SLE.

Osteogenesis Imperfecta: characterization of fractures during pregnancy and post-partum.

BACKGROUND: Pregnancy and breastfeeding are associated with bone density loss. Fracture occurrence during pregnancy and post-partum, and its determinants, remain poorly known in Osteogenesis Imperfecta (OI). The aim of this study was to characterize fractures that occurred during pregnancy and post-partum in OI patients. RESULTS: We conducted a retrospective multicentric study including a total of 50 previously pregnant OI women from 10 Bone Centers in France. Among these patients, 12 (24%) patients experienced fractures during pregnancy or in the 6 months following delivery, and 38 (76%) did not experience any fracture. The most frequent localizations were: proximal femur (25%), spine (25%), distal femur (12.5%), and pelvis (12.5%). Fractures during pregnancy occurred during the third trimester and post-partum fractures occurred with a mean delay of 2 months following delivery. No fractures occurred during childbirth. We next compared the 12 patients with pregnancy or post-partum fractures with the 38 patients without fractures. Mean age at pregnancy was 32.7 ± 3.1 years-old in the fractured group, vs 29.3 ± 5.0 years-old in the non-fractured group (p = 0.002). Breastfeeding was reported in 85.7% of patients in the fractured group, vs 47.1% in the non-fractured group (p = 0.03). All patients with post-partum fractures were breastfeeding. Bone mineral density was significantly lower in patients with pregnancy-related fractures compared with other patients: spine Z-score - 2.9 ± 1.6DS vs - 1.5 ± 1.7DS (p = 0.03), and total hip Z-score - 2.0 ± 0.7DS vs - 0.5 ± 1.4DS (p = 0.04). At least one osteoporosis-inducing risk factor or disease other than OI was identified in 81.8% vs 58.6% of fractured vs non-fractured patients (not significant). Fracture during pregnancy or post-partum was not associated with the severity of OI. Bisphosphonates before pregnancy were reported in 16.7% and 21.1% of patients with pregnancy-related fractures and non-fractured patients, respectively (not significant). CONCLUSIONS: OI management during pregnancy and post-partum should aim for optimal control of modifiable osteoporosis risk factors, particularly in patients with low BMD. Breastfeeding should be avoided.

Randomized Controlled Study of a Training Program for Knee and Shoulder Arthrocentesis on Procedural Simulators with Assessment on Cadavers.

OBJECTIVE: The study objective was to assess the efficacy of simulators in improving the competence of students in performing a knee and shoulder arthrocentesis on cadavers and to determine the minimum number of simulator training procedures needed to achieve competence in arthrocentesis. METHODS: Two groups of 15 medical students were each trained to perform a single joint arthrocentesis ("knee group" and "shoulder group") on a simulator to serve as a control for the other. The two groups received the same theoretical training (anatomy, arthrocentesis techniques, ultrasound, and hybrid simulation). Each student punctured the two joints on a cadaver. A student was considered "competent on the cadaver" if they succeeded at two or more arthrocentesis procedures out of the three tests on the joint on which they were trained. The minimum threshold value to be competent was calculated by a receiver operating characteristic curve and the Youden index. An assessment of theoretical knowledge and confidence level in joint arthrocentesis was carried out at the start and end of the study. RESULTS: Twenty-two out of 29 students (75.8%) achieved competence in arthrocentesis at the joint for which they were trained. Of the students in the knee group, 79% were competent on the cadaver's knee versus 60% of the students in the shoulder group (P = 0.43). Of students in the shoulder group, 74% were competent on the cadaver's shoulder versus 57% of students in the knee group (P = 0.45). Four training punctures on a simulator are necessary to achieve competence on a cadaver. The students' confidence level in arthrocentesis increased significantly during the study, as did the students' theoretical knowledge. CONCLUSION: Knee and shoulder arthrocentesis success rates were not statistically different between the two training groups. A minimum number of 4.0 training arthrocentesis on a simulator is needed to achieve competency on a cadaver.

Clinical phenotype and cytokine profile of adult IgA vasculitis with joint involvement.

OBJECTIVE: Joint involvement can be observed during the course of adult IgA vasculitis (IgAV). However, clinical picture, prognosis, or pathophysiological data associated with this condition have been overlooked. We aimed to describe the clinical characteristics and outcome of IgAV patients with joint involvement and look to a specific cytokine profile. METHODS: We analyzed clinical and biological data from a nationwide study that included adult IgAV patients. Presentation and outcomes of patients with or without joint involvement were compared at baseline and during follow-up. Plasma cytokine measurements of IgAV patients included in a prospective study were also analyzed using multiplex assays. RESULTS: Among 260 patients, 62% had joint involvement. Among them, rheumatological manifestations included arthralgia (100%) or arthritis (16%), mostly involving the knees and ankles. In multivariate analysis, patients with joint involvement, compared to those without, were younger (p = 0.002; OR 0.87; 95% CI 0.80-0.95) and showed more frequent gastrointestinal tract involvement (p = 0.012; OR = 2.08; 95% CI 1.18-3.67). However, no difference in terms of clinical response, relapse, end-stage renal disease, or death was observed between groups. Among 13 cytokines measured, plasma interleukin (IL)-1ß level was higher in patients with joint involvement compared to those without (mean ± SEM IL-1ß, 3.5 ± 1.2 vs. 0.47 ± 0.1 pg/ml; p = 0.024) or healthy controls (vs. 1.2 ± 0.5 pg/ml; p = 0.076). CONCLUSION: Joint involvement is frequent in adult IgAV and is associated with more frequent gastrointestinal involvement. Increased plasma IL-1ß levels raise the question of targeting this cytokine in patients with chronic and/or refractory joint involvement. Key Points • Joint involvement in adult IgAV is a frequent manifestation. • Joint involvement is associated with more frequent gastrointestinal manifestations. • Interleukin-1ß (IL-1ß) might orchestrate joint inflammation in adult IgAV. • IL-1ß might be a therapeutic target in patients with chronic and/or refractory joint involvement.

Description of Joint Alterations Observed in a Family Carrying p.Asn453Ser COMP Variant: Clinical Phenotypes, In Silico Prediction of Functional Impact on COMP Protein and Stability, and Review of the Literature.

The role of genetics in the development of osteoarthritis is well established but the molecular bases are not fully understood. Here, we describe a family carrying a germline mutation in COMP (Cartilage Oligomeric Matrix Protein) associated with three distinct phenotypes. The index case was enrolled for a familial form of idiopathic early-onset osteoarthritis. By screening potential causal genes for osteoarthritis, we identified a heterozygous missense mutation of COMP (c.1358C>T, p.Asn453Ser), absent from genome databases, located on a highly conserved residue and predicted to be deleterious. Molecular dynamics simulation suggests that the mutation destabilizes the overall COMP protein structure and consequently the calcium releases from neighboring calcium binding sites. This mutation was once reported in the literature as causal for severe multiple epiphyseal dysplasia (MED). However, no sign of dysplasia was present in the index case. The mutation was also identified in one of her brothers diagnosed with MED and secondary osteoarthritis, and in her sister affected by an atypical syndrome including peripheral inflammatory arthritis of unknown cause, without osteoarthritis nor dysplasia. This article suggests that this mutation of COMP is not only causal for idiopathic early-onset osteoarthritis or severe MED, but can also be associated to a broad phenotypic variability with always joint alterations.

Valvular and infection-associated risk factors as criteria to guide the use of echocardiography in patients with native joint infections.

BACKGROUND: Native joint and bone infections (NJBI) are associated with infective endocarditis (IE) in 15% of cases. There are no studies analyzing the use of cardiac imaging in cases of NJBI. The objective of this study was to identify factors associated with echocardiography suggestive of IE in patients with NJBI. METHODS: This medical records review was conducted in patients hospitalized for NJBI between 2007 and 2017 in Rheumatology and Infectious Diseases departments of 2 university hospitals. Patients included had a microbiologically proven NJBI during their hospitalization. RESULTS: In this cohort of 546 patients, median age 66 years, echocardiography was suggestive of IE in 66 (12%). In multivariate analysis, factors associated with echocardiography suggestive of IE were 2 or more positive blood cultures (OR 11.55 (CI95% 3.24-74.20)), cardiac conditions with a high risk of IE (OR 7.34 (CI95% 2.95-18.61)), unknown heart murmur (OR 4.59 (CI95% 1.79-11.74)), multifocal infection (OR 2.26 (CI95% 1.21-4.23)) and an infection due to S. bovis (OR 3.52 (CI95% 1.26-9.79)). The factor associated with the absence of an echocardiography evocative of IE was infection due to unconventional bacteria for IE (OR 0.13 (CI95% 0.01-0.76)). According to the factors associated with echocardiography evocative of IE, we propose the Normandy score based on three kinds of data: cardiac condition, bacterial strain and NJBI mechanism. Echocardiography should be realized when this score, whose negative predictive value is 100% CI95% (98-100%) for prescription of echocardiography, is more than zero. CONCLUSIONS: A score based on valvular condition, bacterial strain and NJBI mechanism could guide clinicians in prescribing echocardiography during NJBI with an excellent negative predictive value.

Epidemiology of Injuries in Elite Badminton Players: A Prospective Study.

OBJECTIVE: To determine the incidence and characteristics of injuries in elite badminton players over a competitive season. DESIGN: Prospective cohort study. SETTING: The French National Institute of Sport, Expertise, and Performance (INSEP). PARTICIPANTS: Twenty international elite badminton players. INDEPENDENT VARIABLES: The type, the location, the occurrence of the injury (match or training), the footwork type, the type of shot, and the perceived fatigue were collected. MAIN OUTCOME MEASURES: Injury incidence rates were calculated per 1000 hours of play (Hop). RESULTS: Thirty-five injuries were collected over 10 210 hours of player exposure with an overall incidence rate of 3.4 injuries per 1000 Hop, with higher incidence during matches than training (11.6 vs 2.08; P < 0.05). Lower-limb injuries (LLI) were the most frequent (54.3%) especially on the foot (22.9%), and upper-limb injury rate (37.1%) was higher compared with previous studies. The most common type was musculotendinous injuries (51.4%). The smash and the lunge were the most frequent causes of upper-limb injury and LLI, respectively. Injuries occurred mostly during the first third of play (46.2%). CONCLUSIONS: This is the first prospective study to investigate badminton injuries among international badminton players. Further studies are needed to confirm our results on larger samples.

Rhupus: a systematic literature review.

"Rhupus" or "rhupus syndrome" is a poorly described and underdiagnosed disease in which features of both rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE) appear in the same patient, most often sequentially. The SLE-related involvement is usually mild, dominated by hematological abnormalities and skin, serosal and renal involvement. The natural history of rhupus arthritis follows an RA-like pattern and can progress towards typical inflammatory erosions, deformations and disability. Despite the lack of consensus on the definition of rhupus and on its place in the spectrum of autoimmunity, a growing number of studies are pointing towards a true overlap between RA and SLE. However, the inclusion criteria employed in the literature during the last 4 decades are heterogeneous, making the already rare cohorts and case reports difficult to analyze. Because of this heterogeneity and due to the rarity of the disease, the prevalence, pathophysiology and natural history as well as the radiological and immunological profiles of rhupus are poorly described. Moreover, since there is no validated therapeutic strategy, treatment is based on clinicians' experience and on the results of a few studies. We herein present a systematic literature review to analyze the clinical and laboratory data of all reported rhupus patients and to provide up-to-date information about recent advances in the understanding of the pathophysiological mechanisms, diagnostic tools and treatment options.

Safety of surgery in patients with rheumatoid arthritis treated with tocilizumab: data from the French (REGistry -RoAcTEmra) Regate registry.

OBJECTIVES: To investigate the frequency and risk factors of postoperative complications in RA patients treated with tocilizumab (TCZ). METHODS: The French registry REGATE recruited 1496 RA patients receiving TCZ in routine care. Data from patients treated with TCZ who underwent surgery were reviewed. Frequency of post-surgery complications was collected and compared in patients with and without complications in order to identify factors associated with complications. Similar analysis was performed in patients with postoperative infection. RESULTS: We identified 167 patients who underwent 175 surgical procedures including 103 orthopaedic surgeries (58.9%). The patients were mainly women (84%) with a mean disease duration of 14.96±11.29 years. The mean delay between surgery and the last TCZ infusion was 4.94±1.74 weeks. Fifteen patients experienced 15 complications (8.6%) with 10 severe infections including 5 surgical site infections (33.3%). There was no significant difference between patients with and without complications. In multivariate analysis, previous treatment with rituximab in the previous year tended to be associated with postoperative complications (OR: 3.27, IC95% 0.92-11.49, p=0.06). Concerning postoperative infections, diabetes mellitus tended to be associated with this complication (OR: 3.73, IC95% 0.88-15.79, p=0.06) in multivariate analysis. CONCLUSIONS: In RA patients treated with TCZ in perfusion, the rate of surgical complications was low: 8.6%. The median time between surgery and last infusion was relatively short according to half-life of TCZ but did not influence the rate of postoperative complications.

Adverse Effects of Anticholinergic Drugs on Cognition and Mobility: Cutoff for Impairment in a Cross-Sectional Study in Young-Old and Old-Old Adults.

BACKGROUND: Drugs with anticholinergic properties are commonly prescribed in older adults despite growing evidence of their adverse outcomes. Several issues regarding these detrimental effects remain unresolved, such as the putative existence of a threshold above which anticholinergic drug consumption impairs cognitive or mobility performance. OBJECTIVES: We aimed to investigate the number of anticholinergic drugs and the anticholinergic burden that leads to mobility or cognitive impairment and compare the effects in community-dwelling older adults in two age groups ("young-old" 55-74 vs. "old-old" ≥ 75 years). METHODS: In a cross-sectional study, we identified drugs with anticholinergic (antimuscarinic) properties using the Anticholinergic Drug Scale. Cognition was assessed using the Mini Mental State Examination (MMSE) and the Trail Making Test (TMT-A and TMT-B), and mobility was assessed using the Timed Up and Go (TUG) test. RESULTS: The study population consisted of 177 volunteers, 114 of whom were classed as young-old and 63 were classed as old-old adults. Despite the lack of cutoff values for impaired outcomes in young-old adults, impaired MMSE were significantly more numerous in users than in nonusers of anticholinergic drugs. In old-old adults, receiver operating characteristic (ROC) curve analysis indicated that taking a single anticholinergic drug per day was associated with impaired TMT-B completion time, TMT difference score (B-A), and TUG scores. The cutoff for anticholinergic burden was also one for these same outcomes. Based on these cutoff values, multivariate logistic regressions in old-old adults showed that the increased risk of impaired cognition and mobility was independent of confounding factors, including comorbidities. They also suggested that anticholinergic drugs would affect mobility through executive functions. CONCLUSIONS: Drugs with anticholinergic (antimuscarinic) properties are associated with cognitive impairment in individuals as young as 55 years, and only one such drug per day, regardless of its anticholinergic burden, is associated with both impaired cognition and impaired mobility in old-old adults. Therefore, wherever possible, clinicians should avoid prescribing drugs with anticholinergic properties.

Knee replacement incidence and social deprivation: results from a French ecological study.

OBJECTIVES: Temporal and geographic variations in knee osteoarthritis (OA) incidence occur worldwide. Regional variations also exist for socioeconomic status. We analyzed the association between socioeconomic deprivation (SED) and knee replacement (KR) incidence and assessed the proportion of KR associated with affluence. METHODS: Patients aged 15 years and over hospitalized for KR in 2013 were included. We linked each patient to a municipality of residence. Municipalities were matched to the 2011 European Deprivation Index score for SED analysis. Poisson regression was performed to examine the association between KR incidence and EDI adjusted for age and sex. The Population Attributable Fraction (PAF) was measured to calculate the proportion of excess of KR associated with social affluence. RESULTS: We included 77 597 KR. KR incidence decreased with increasing SED index. The EDI was significantly associated with KR incidence (P < 0.0001). The risk of KR is 2.36 times higher for persons living in the most affluent area compared to those living in the most underprivileged area. The PAF was 28.3%. CONCLUSIONS: The French administrative municipalities with the highest SED have the lowest age- and sex-adjusted KR incidence. It cannot be excluded that patients living in more privileged areas are overtreated. Complementary studies are necessary to define all the individual factors that limit or increase the access to knee replacement.

Reduced gait and postural stability under challenging conditions in fallers with upper limb fracture.

BACKGROUND: While most fractures are caused by falls, not all falls result in fractures. Risk factors for falls are well established, but only weak associations have been demonstrated for risk factors for fractures. Conflicting results on the implication of bone mineral density (BMD) suggest that other risk factors should be studied, such as gait and balance disorders. AIMS: Gait and postural stability in challenging conditions were, therefore, compared between fallers with and without fracture. METHODS: We enrolled 80 adults aged 55 and older who fell in the previous year. We compared gait and posture after obstacle crossing between fallers with an upper-limb fracture (n = 38), and fallers without fracture (n = 42). Data on BMD, body mass index, handgrip strength, fear of falling, number of comorbidities, number of falls, global cognition, executive functioning and education level were collected. RESULTS: Compared to fallers without fracture, fallers with fracture had significant lower gait velocity (Likelihood-Ratio = 4.93; P = 0.03) and lower postural stability during stabilization after obstacle crossing (Likelihood-Ratio = 10.99; P < 0.001). In addition, fallers with fracture had lower handgrip strength (Likelihood-Ratio = 9.92; P = 0.002), lower education level (Likelihood-Ratio = 8.32; P = 0.004), poorer executive functions (Likelihood-Ratio = 5.81; P = 0.02, higher fear of falling (Likelihood-Ratio = 5.55; P = 0.02) and were more likely women (Likelihood-Ratio = 17.55; P < 0.001), compared to fallers without fracture. DISCUSSION: This study demonstrated that the main difference between fallers with upper-limb fracture and fallers without fracture is mobility in dynamic condition. Poor executive function and low muscular strength could also be involved. CONCLUSIONS: These factors should be taken into account when assessing risk factors for fracture and implementing preventive programs. CLINICAL TRIAL REGISTRATION: clinicaltrials.gov. NCT02292316.

Psychotropic Polypharmacy in Adults 55 Years or Older: A Risk for Impaired Global Cognition, Executive Function, and Mobility.

OBJECTIVES: With their broad spectrum of action, psychotropic drugs are among the most common medications prescribed to the elderly. Consequently, the number of older adults taking multiple psychotropic drugs has more than doubled over the last decade. To improve knowledge about the deleterious effects of psychotropic polypharmacy, we investigated whether there is a threshold number of psychotropic molecules that could lead to impairment of global cognition, executive function, or mobility. Furthermore, relationships between the number of psychotropic molecules and cognitive and mobility impairment were examined. DESIGN: Cross-sectional study. SETTING: University Hospital of Caen (France) and advertisements in medical offices. PARTICIPANTS: Community-dwelling older adults 55 years and older (n = 177; 69.8 ± 9.3 years; 81% women). MEASUREMENTS: Number of psychotropic molecules taken daily, global cognition assessed with the Mini Mental State Examination (MMSE) and the Montreal Cognitive Assessment (MoCA), processing speed with the Trail Making Test (TMT) A, executive function with the TMT B and TMT B-A, and mobility with the Time Up and Go (TUG). The threshold numbers of psychotropic molecules were determined by ROC curves analysis. Based on these threshold values, multinomial logistic regression adjusting for covariates was then performed. RESULTS: Logistic regressions showed that the threshold of two daily psychotropic molecules, identified by the ROC curves analysis, increases the risk of impaired executive function (p = .05 and.005 for the TMT B and TMT B-A, respectively), global cognition (p = .006 and.001 for the MMSE and MoCA, respectively), and mobility (p = .005 for the TUG), independent of confounding factors, including comorbidities. Furthermore, psychotropic polypharmacy would affect mobility through executive functions. CONCLUSION: Impairment of global cognition, executive function, and mobility when as few as two psychotropic molecules are consumed in relatively healthy young older adults should alert physicians when prescribing combinations of psychotropic medications.