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Background: Mutations in the LRRK2 gene are the most common genetic cause of Parkinson disease but are believed to play no significant role in Lewy body disease (LBD)., Objectives: As the frequency of G2019S LRRK2 mutation is extremely high in North African patients with Parkinson disease, we postulate that the high prevalence of LBD in North Africa might be due to the same mutation because LBD and Parkinson disease share many clinical, pathological, and genetic features., Methods: We screened patients with LBD or prodromal LBD for the G2019S mutation of LRRK2., Results: A total of 162 patients were tested for the mutation, which was present in 5 of the 47 patients with North African ancestors. This is a much higher prevalence (10.6%) than in healthy North African subjects (1.45%) but lower than in North African patients with Parkinson disease (36% to 39%). Carriers tended to develop more often orthostatic hypotension and swallowing problems., Conclusions: Where previous studies in European and North American patients found no link between LRRK2 mutations and LBD, we found an LRRK2 mutation associated with Lewy body disease, namely the G2019S mutation that might be restricted to patients with North African ancestors. Our study illustrates the need to introduce ethnic diversity as stratifying factor in the analysis of genetic causes of neurodegenerative disorders. The current development of disease-modifying drugs modulating LRRK2 kinase activity could justify to screen North African patients with LBD for the G2019S LRRK2 mutation., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

This scoping review was conducted to identify the outcomes and measurement tools used in IC intervention studies, as first step towards the development of a core outcome set (COS) for IC trials. PRISMA-ScR and COS-STAD were followed. The review considered randomized controlled trials targeting IC published in Medline, Scopus, Embase, Cochrane Central Register of Controlled Trials, and clinicaltrials.gov, until June 2023. Of 699 references, 534 studies were screened once duplicates were removed, 15 were assessed for eligibility, and 7 (4 articles and 3 protocols) met eligibility criteria. Twenty-eight outcomes were identified (19 related to IC and its domains and 9 unrelated). The most reported primary outcome was the change in IC levels postintervention (5 over 7 studies) and the most reported outcomes (either as primary and/or secondary) were the changes in physical performance and in depressive symptoms (6 over 7 studies). Fifty-five tools used to construct the domains' z-scores and/or assess the effect of interventions were identified (47 related to IC and its domains and 8 unrelated). The most reported tool was an IC Z-score, calculated by 4 domains' z-scores: locomotor, vitality, cognitive, and psychological (5 over 7 studies). The tools differed among studies (10 locomotor related, 6 vitality related, 16 cognitive related, 8 psychological related, 6 sensorial related, 8 unrelated tools). The vast heterogeneity (28 outcomes and 55 tools within 7 studies) highlighted the need of a COS. These outcomes and tools will be presented to experts in a future step, to select the ones that should be taken into consideration in IC trials., (© 2024. The Author(s).)

Objective: To determine whether the Geriatric Nutritional Risk Index (GNRI) on hospital admission was associated to an increased 14-day and 12-month mortality-risk in older inpatients with COVID-19., Methods: Cohort study of consecutive inpatients admitted with COVID-19 in a university hospital (20/03/2020-11/05/2021)., Inclusion Criteria: age over 65 years and positive polymerase chain reaction test., Exclusion Criteria: missing data for weight, height, and/or albumin, hospital-acquired COVID-19, or patients transferred to other health facilities., Outcome: all-cause mortality at 14-day and 12-month follow-up. GNRI [1.489 × albumin (g/L)] + [41.7 (weight/ideal body weight)] was assessed at admission; scores ≤98 indicated risk of malnutrition. Cox-proportional hazards models assessed the association between the admission GNRI and 14-day and 12-month mortality-risk, after adjusting by demographic and clinical variables, including inflammation (C-reactive protein)., Results: Of the 570 eligible patients, 224 (mean age 78 years; 52.2% women) met inclusion criteria and 151 (67.4%) were classified at risk of malnutrition. Twenty patients died during the 14-day and 42 during the 12-month follow-up. The risk of 14-day mortality was nearly 10 times higher in patients with GNRI scores ≤98 (HR = 9.6 [95%CI 1.3-71.6], P = 0.028); this association was marginally significant in the adjusted model (HR = 6.73 [95%CI 0.89-51.11], P = 0.065)]. No association between GNRI and the 12-month mortality-risk was found., Conclusions: The GNRI may play a role in the short-term prognosis of older inpatients with COVID-19. Further studies are required to confirm the short-term predictive validity of the GNRI within this population (Clinicaltrials.gov_NCT05276752)., Competing Interests: Declaration of competing interest Dolores Sánchez-Rodríguez serves as an Associated Editor of Clinical Nutrition ESPEN and as Senior Advisor to the World Health Organization (WHO) Collaborating Center for Epidemiology of Musculoskeletal Health and Aging, Division of Public Health, Epidemiology, and Health Economics, University of Liège, Liège, Belgium. The authors declare there are no actual or potential conflicts of interest related to this article., (Copyright © 2023 European Society for Clinical Nutrition and Metabolism. Published by Elsevier Ltd. All rights reserved.)

Only previous glucocorticoid use and rheumatoid arthritis were predictors of an early fracture (< 2 years after inclusion). A shorter 'time to first fracture' was not an independent clinical risk factor for imminent fractures., Purpose: Risk factors for fragility fractures independent of BMD were assessed in several prediction models. However, predictors of a shorter 'time to first fracture' and its impact on imminent fractures are unknown., Methods: We studied the concept of 'time to first fracture' in the FRISBEE ("Fracture RIsk Brussels Epidemiological Enquiry") cohort (3560 postmenopausal women). Validated fractures were divided into 3 groups: first fracture < 2 years, 2-5 years, and > 5 years after inclusion. Factors associated with first fracture risk were evaluated with uni- and multivariate analyses using Cox modeling. We examined 'time to first fracture' as a risk factor for imminent fractures in untreated subjects and in those receiving pharmacological treatment., Results: Classical risk factors (age, prior fracture, fall history and low BMD) were associated with first fracture in all groups. Previous glucocorticoids and rheumatoid arthritis (RA) were predictors for fracture < 2 years. Imminent fractures were similar in subjects with or without osteoporosis treatment, despite a higher estimated 10-year risk of fragility fracture in those treated, suggesting that treatment is efficient. 'Time to first fracture' was not an independent risk factor for imminent fractures., Conclusion: Among the risk factors considered, previous glucocorticoid use and RA were predictors for early fracture, consistent with the concept of very high risk. The 'time to first validated fracture' was not an independent risk factor for imminent fractures. Patients with a first osteoporotic fracture should thus be considered at very high risk for re-fracture, independent of the 'time to first fracture'., (© 2023. International Osteoporosis Foundation and Bone Health and Osteoporosis Foundation.)

Background and Purpose: The establishment of cognitive fluctuations is important when dementia with Lewy bodies (DLB) is suspected but can be especially difficult in the absence of a caregiver who lives with the patient. We examined the possibility of using fluctuating scores on a forward (FDS) and a backward digit span (BDS) test as a marker for cognitive fluctuation., Methods: Patients with DLB (21), other forms of dementia (14 with Alzheimer's disease, 8 with vascular dementia) and 20 controls were asked to perform an FDS and BDS twice, with an interval of 20 min., Results: Seventy percent of patients with DLB showed evidence of cognitive fluctuations for at least one test, while less than 10% of controls and patients with other dementias did. Evidence of cognitive fluctuations on at least one of both tests classified 83% of patients correctly (i.e. DLB or not), with a sensitivity of 70% and a specificity of 90%., Conclusions: Repeated forward and backward digit span tests seem a valid, short, easy and inexpensive bedside tool to detect cognitive fluctuations in the diagnostic work-up of DLB, even in the absence of a caregiver, which limits the use of questionnaires., (© 2023. The Author(s) under exclusive licence to Belgian Neurological Society.)

The Global Leadership Initiative on Malnutrition (GLIM) criteria were introduced in 2018 for the diagnosis of malnutrition in adults. This review was aimed at gathering the evidence about the association between malnutrition according to the GLIM criteria and mortality in older people, an emerging and clinically meaningful topic in the implementation of the GLIM criteria in geriatric healthcare settings. This scoping review considered meta-analyses, systematic reviews, cohort studies, and cross-sectional studies published in PubMed, Scopus, and the Cochrane Database for Systematic Reviews from the development of the GLIM criteria in 2018 to January 2023. Seventeen articles (15 cohort and 2 cross-sectional studies) were included. The association between GLIM criteria and mortality had been assessed in hospitalized (11 over the 17 articles) and community-dwelling older populations, and those in nursing homes. The review found a strong association between malnutrition according to GLIM criteria and mortality in hospitalized (1.2-fold to 7-fold higher mortality) and community-dwelling older people (1.6-fold to 4-fold higher mortality). These findings highlight the prognostic value of the GLIM criteria and support strategies towards the implementation of malnutrition evaluation according to the GLIM, in order to optimize comprehensive geriatric assessment and provide older people with the highest quality of nutritional care. Studies in nursing home populations were very scarce and may be urgently required.

Five-year fracture risk prediction from the Fracture Risk Brussels Epidemiological Enquiry (FRISBEE) models was externally tested in 9716 Canadian women and demonstrated good discrimination but consistently overestimated risk., Introduction: Five-year risk prediction models for all fractures, major osteoporotic fractures (MOFs) and central fractures (proximal to forearm and ankle) from the FRISBEE cohort demonstrated good performance in the original derivation cohort. Our aim was to externally validate the FRISBEE-based 5-year prediction models in routine practice., Methods: Using the population-based Manitoba Bone Mineral Density (BMD) registry, we identified women aged 60-85 years undergoing baseline BMD assessment from September 1, 2012 to March 31, 2018. Five-year probabilities of all fractures, MOFs and central fractures were calculated using the FRISBEE prediction models. We identified incident non-traumatic fractures up to 5 years from population-based healthcare data sources. Performance characteristics included area under the receiver operating characteristic curve (AUROC), gradient of risk (hazard ratio [HR] per SD increase and across risk tertiles) from Cox regression analysis, and calibration (ratio 5-year observed cumulative incidence to predicted fracture probability)., Results: We included 9716 women (mean age 70.7 + / - SD 5.3 years). During a mean observation time of 2.5 years, all fractures, MOFs and central fractures were identified in 377 (3.9%), 264 (2.7%) and 259 (2.7%) of the women. AUROC showed significant fracture risk stratification with the FRISBEE models (all fractures 0.69 [95%CI 0.67-0.72], MOFs 0.71 [95%CI 0.68-0.74], central fractures 0.72 [95%CI 0.69-0.75]). There was a strong gradient of risk for predicting fracture outcomes per SD increase (HRs from 1.98 to 2.26) and across risk tertiles (HRs for middle vs lowest from 2.25 to 2.41, HRs for highest vs lowest from 4.70 to 6.50). However, risk was overestimated for all fractures (calibration-in-the-large 0.63, calibration slope 0.63), MOF (calibration-in-the-large 0.51, calibration slope 0.57) and central fractures (calibration-in-the-large 0.55, calibration slope 0.60)., Conclusions: FRISBEE 5-year prediction models were externally validated to stratify fracture risk similar to the derivation cohort, but would need recalibration for Canada as risk was overestimated., (© 2022. International Osteoporosis Foundation and Bone Health and Osteoporosis Foundation.)

Context: Individualized fracture risk may help to select patients requiring a pharmacological treatment for osteoporosis. FRAX and the Garvan fracture risk calculators are the most used tools, although their external validation has shown significant differences in their risk prediction ability., Objective and Methods: Using data from the Fracture Risk Brussels Epidemiological Enquiry study, a cohort of 3560 postmenopausal women aged 60 to 85 years, we aimed to construct original 5-year fracture risk prediction models using validated clinical risk factors (CRFs). Three models of competing risk analysis were developed to predict major osteoporotic fractures (MOFs), all fractures, and central fractures (femoral neck, shoulder, clinical spine, pelvis, ribs, scapula, clavicle, sternum)., Results: Age, a history of fracture, and hip or spine BMD were predictors common to the 3 models. Excessive alcohol intake and the presence of comorbidities were specific additional CRFs for MOFs, a history of fall for all fractures, and rheumatoid arthritis for central fractures. Our models predicted the fracture probability at 5 years with an acceptable accuracy (Brier scores ≤ 0.1) and had a good discrimination power (area under the receiver operating curve of 0.73 for MOFs and 0.72 for central fractures) when internally validated by bootstrap. Three simple nomograms, integrating significant CRFs and the mortality risk, were constructed for different fracture sites. In conclusion, we derived 3 models predicting fractures with an acceptable accuracy, particularly for MOFs and central fractures. The models are based on a limited number of CRFs, and we constructed nomograms for use in clinical practice., (© The Author(s) 2022. Published by Oxford University Press on behalf of the Endocrine Society.)

Objective: We aimed at assessing the association between demographical and clinical data and the intrahospital mortality in older patients with COVID-19 in Belgium., Methods: Descriptive, retrospective study of consecutive patients admitted to Brugmann university hospital, Brussels (Belgium) due to COVID-19 (Mars-September-2020)., Inclusion Criteria: Patients aged ≥ 70 years admitted to acute care with a positive PCR-RT test, or a highly indicative computed tomography scan., Exclusion Criteria: Patients transferred to another institution during hospitalization., Outcome Measure: All-cause intrahospital mortality. Demographic, clinical data, presence of comordibidties and comprehensive geriatric assessment were collected. Adjusted and unadjusted logistic regression were performed., Results: From the 226 eligible patients, 160 (82.7 ± 6.5-year-old; 57.5 % females) met inclusion criteria, from which 67 (42 %) died during hospital stay. The adjusted logistic regression showed an association between intrahospital mortality and increasing age [OR = 1.09 per every year increase (95 % CI 1.02-1.16); p <0.001], type 2 diabetes [OR = 2.75 ( 1.17-6.46); p = 0.021], and acute respiratory distress syndrome (ARDS) [OR = 8.67 ( 3.48-21.61); p < 0.01]., Conclusions: A higher positive association between intrahospital mortality and increasing age, type 2 diabetes, and ARDS was found. The prognosis value of the comprehensive geriatric assessment in older people with COVID-19 in Belgium requires further studies.