Treatment Effect of the SGLT2 Inhibitor Empagliflozin on Chronic Syndrome of Inappropriate Antidiuresis: Results of a Randomized, Double-Blind, Placebo-Controlled, Crossover Trial.

BACKGROUND: The syndrome of inappropriate antidiuresis (SIAD) is characterized by a reduction of free water excretion with consecutive hypotonic hyponatremia and is therefore challenging to treat. The sodium-glucose cotransporter 2 (SGLT2) inhibitor empagliflozin promotes osmotic diuresis via urinary glucose excretion, likely leading to increased electrolyte free water clearance. METHODS: In this randomized, double-blind, placebo-controlled, crossover trial, we compared 4-week treatment with empagliflozin 25 mg/d to placebo in outpatients with chronic SIAD-induced hyponatremia. At baseline and after both treatment cycles, patients underwent different assessments including neurocognitive testing (Montreal Cognitive Assessment [MoCA]). The primary end point was the difference in serum sodium levels between treatments. RESULTS: Fourteen patients, 50% female, with a median age of 72 years (interquartile range [IQR], 65-77), completed the trial. Median serum sodium level at baseline was 131 mmol/L (IQR, 130-132). After treatment with empagliflozin, median serum sodium level rose to 134 mmol/L (IQR, 132-136), whereas no increase was seen with placebo (130 mmol/L; IQR, 128-132), corresponding to a serum sodium increase of 4.1 mmol/L (95% confidence interval [CI], 1.7 to 6.5; P =0.004). Exploratory analyses showed that treatment with empagliflozin led to improved neurocognitive function with an increase of 1.16 (95% CI, 0.05 to 2.26) in the MoCA score. Treatment was well tolerated; no serious adverse events were reported. CONCLUSION: The SGLT2 inhibitor empagliflozin is a promising new treatment option for chronic SIAD-induced hyponatremia, possibly improving neurocognitive function. Larger studies are needed to confirm the observed treatment effects. CLINICAL TRIAL REGISTRATION NUMBER: ClinicalTrials.gov NCT03202667. PODCAST: This article contains a podcast at.

Neural Correlates of Stepping in Healthy Elderly: Parietal and Prefrontal Cortex Activation Reflects Cognitive-Motor Interference Effects.

Gait analysis involving cognitive-motor dual task (DT) is a diagnostic tool in geriatrics. Cognitive-motor interference effects during DT, such as decreased walking speed and increased step-to-step variability, have a high predictive value for fall risk and cognitive decline. Previously we showed the feasibility of DT during functional magnetic resonance imaging (fMRI) using an MRI-compatible stepping device. Here, we improved the DT-fMRI protocol with respect to task difficulty and signal robustness, making it more suitable for individualized analysis to better understand the neuronal substrates of cognitive-motor interference effects. Thirty healthy elderly subjects performed cognitive and motor single tasks (ST; stepping or finger tapping), as well as combined cognitive-motor DT during fMRI. After whole brain group level analysis, a region-of-interest (ROI) analysis and the computation of dual task costs (DTC = activation difference ratio ST/DT) at individual level were performed. Activations in the primary (M1) and secondary motor as well as in parietal and prefrontal cortex were measured at the group level during DT. Motor areas showed decreased activation whereas parietal and prefrontal areas showed increased activation in DT vs. ST. Stepping yielded more distinctive activations in DT vs. ST than finger tapping. At the individual level, the most robust activations (based on occurrence probability and signal strength) were measured in the stepping condition, in M1, supplementary motor area (SMA) and superior parietal lobule/intraparietal sulcus (SPL/IPS). The distribution of individual DTC in SPL/IPS during stepping suggested a separation of subjects in groups with high vs. low DTC. This study proposes an improved cognitive-motor DT-fMRI protocol and a standardized analysis routine of functional neuronal markers for cognitive-motor interference at the individual level.

[Vitamin D Level in Employees of a Swiss University Geriatric Hospital]. / Vitamin-D-Status bei Mitarbeitenden eines universitären Schweizer Geriatriespitals.

Vitamin D Level in Employees of a Swiss University Geriatric Hospital Abstract. Vitamin D plays an important role in health. The aim of this study was to determine the vitamin D level in hospital employees from different age, sex and occupational groups. 281 employees took part in the investigation. Vitamin D (25-OH) was determined by serum sample analysis, the mean value was 59.5 nmol/l. 43.1 % of participants showed a vitamin D deficiency (<50 nmol/l). Low vitamin D levels significantly correlated with increased BMI. Women, physically active employees and those in occupations with medical content had significantly higher vitamin D levels. Sports activity and substitution were independent predictors of vitamin D level. The study illustrated that increased sun exposure and/or vitamin D supplementation are needed.

Validity of the German Version of the Continuous-Scale Physical Functional Performance 10 Test.

BACKGROUND: The Continuous-Scale Physical Functional Performance 10 Test (CS-PFP 10) quantitatively assesses physical functional performance in older adults who have a broad range of physical functional ability. This study assessed the validity and reliability of the CS-PFP 10 German version. METHODS: Forward-translations and backtranslations as well as cultural adaptions of the test were conducted. Participants were German-speaking Swiss community-dwelling adults aged 64 and older. Concurrent validity was assessed using Pearson correlation coefficients between CS-PFP 10 and gait velocity, Timed Up and Go Test, hand grip strength, SF-36 physical function domain, and Freiburger Physical Activity Questionnaire. Internal consistency was calculated by Cronbach's alpha. RESULTS: Backtranslation and cultural adaptions were accepted by the CS-PFP 10 developer. CS-PFP 10 total score and subscores (upper body strength, upper body flexibility, lower body strength, balance and coordination, and endurance) correlated significantly with all measures of physical function tested. Internal consistency was high (Cronbach's alpha 0.95-0.98). CONCLUSION: The CS-PFP 10 German version is valid and reliable for measuring physical functional performance in German-speaking Swiss community-dwelling older adults. Quantifying physical function is essential for clinical practice and research and provides meaningful insight into physical functional performance of older adults. This trial is registered with ClinicalTrials.gov NCT01539200.

Imaging gait analysis: An fMRI dual task study.

INTRODUCTION: In geriatric clinical diagnostics, gait analysis with cognitive-motor dual tasking is used to predict fall risk and cognitive decline. To date, the neural correlates of cognitive-motor dual tasking processes are not fully understood. To investigate these underlying neural mechanisms, we designed an fMRI paradigm to reproduce the gait analysis. METHODS: We tested the fMRI paradigm's feasibility in a substudy with fifteen young adults and assessed 31 healthy older adults in the main study. First, gait speed and variability were quantified using the GAITRite© electronic walkway. Then, participants lying in the MRI-scanner were stepping on pedals of an MRI-compatible stepping device used to imitate gait during functional imaging. In each session, participants performed cognitive and motor single tasks as well as cognitive-motor dual tasks. RESULTS: Behavioral results showed that the parameters of both gait analyses, GAITRite© and fMRI, were significantly positively correlated. FMRI results revealed significantly reduced brain activation during dual task compared to single task conditions. Functional ROI analysis showed that activation in the superior parietal lobe (SPL) decreased less from single to dual task condition than activation in primary motor cortex and in supplementary motor areas. Moreover, SPL activation was increased during dual tasks in subjects exhibiting lower stepping speed and lower executive control. CONCLUSION: We were able to simulate walking during functional imaging with valid results that reproduce those from the GAITRite© gait analysis. On the neural level, SPL seems to play a crucial role in cognitive-motor dual tasking and to be linked to divided attention processes, particularly when motor activity is involved.

Ginkgo biloba special extract LI 1370 improves dual-task walking in patients with MCI: a randomised, double-blind, placebo-controlled exploratory study.

BACKGROUND: In patients with mild cognitive impairment (MCI), gait instability, particularly in dual-task situations, has been associated with impaired executive function and an increased fall risk. Ginkgo biloba extract (GBE) could be an effective mean to improve gait stability. AIMS: This study investigated the effect of GBE on spatio-temporal gait parameters of MCI patients while walking under single and dual-task conditions. METHODS: Fifty patients aged 50-85 years with MCI and associated dual-task-related gait impairment participated in this randomised, double-blind, placebo-controlled, exploratory phase IV drug trial. Intervention group (IG) patients received GBE (Symfona® forte 120 mg) twice-daily for 6 months while control group (CG) patients received placebo capsules. A 6-month open-label phase with identical GBE dosage followed. Gait was quantified at months 0, 3, 6 and 12. RESULTS: After 6 months, dual-task-related cadence increased in the IG compared to the CG (p = 0.019, d = 0.71). No significant changes, but GBE-associated numerical non-significant trends were found after 6-month treatment for dual-task-related gait velocity and stride time variability. DISCUSSION: Findings suggest that 120 mg of GBE twice-daily for at least 6 months may improve dual-task-related gait performance in patients with MCI. CONCLUSIONS: The observed gait improvements add to the understanding of the self-reported unspecified improvements among MCI patients when treated with standardised GBE.

Dizziness and Unstable Gait in Old Age: Etiology, Diagnosis and Treatment.

BACKGROUND: Dizziness and unsteady gait are common in the elderly but are too often dismissed as supposedly nonspecific, inevitable accompaniments of normal aging. For many affected persons, the factors leading to dizziness and gait impairment in old age are never identified, yet some of these factors can be specifically detected and treated. METHODS: This review is based on publications (2005-2014) retrieved by a selective search in PubMed on the terms "aging," "dizziness," "elderly," "gait," "gait disorder," "geriatric," "locomotion," and "vertigo." RESULTS: Dizziness interferes with the everyday activities of 30% of persons over age 70 and is so severe that it constitutes a reason for consulting a physician. The more common causes of dizziness and unsteady gait in old age are sensory deficits, such as bilateral vestibular failure, polyneuropathy, and impaired visual acuity; benign paroxysmal positioning vertigo; and central disorders such as cerebellar ataxia and normal-pressure hydrocephalus. Further relevant factors include sedative or antihypertensive medication, loss of muscle mass (sarcopenia), and fear of falling. Many elderly persons have multiple factors at the same time. Benign paroxysmal positioning vertigo can be effectively treated with specific physical maneuvers. Sedating drugs are indicated only for the treatment of acute rotatory vertigo and are not suitable for long-term use. Sarcopenia can be treated with physical training. CONCLUSION: If a specific cause can be identified, dizziness and gait unsteadiness in old age can often be successfully treated. The common causes can be revealed by systematic clinical examination. Controlled clinical trials on the efficacy of treatments for elderly persons are urgently needed.

[Cognition and mobility]. / Kognition und Motorik.

Felix Platter Hospital, University Center for Medicine of Aging, Basel, Switzerland; There is a strong association between cognition and mobility. Older adults with gait deficits have an increased risk of developing cognitive deficits, even dementia. Cognitive deficits, on the other hand, are associated with worsening gait. Cognitive as well as mobility deficits are associated with an increased fall risk. Assessments of cognition, particularly the executive functions, and functional mobility should therefore be an integral part of every comprehensive geriatric assessment. Some quick screening tests for mobility disorders can be performed in a clinical praxis. If those assessments provide pathological results, then consider patient referral for an in-depth gait analysis. Gait analyses that utilize dual task paradigms (walking and simultaneously performing a second task) are particularly meaningful for early detection of mobility and cognitive deficits. Early detection permits timely implementation of targeted interventions to improve gait and brain function.

Motor cognitive dual tasking: early detection of gait impairment, fall risk and cognitive decline.

BACKGROUND: Gait and cognition are closely associated. Older adults with gait deficits have an increased risk of developing cognitive deficits and cognitive deficits are associated with worsened gait. Both gait and cognitive impairments are risk factors for falls in older adults. OBJECTIVES: The aims of this article are (1) to highlight the association between gait and cognition, particularly executive function, (2) to present motor cognitive dual tasking test paradigms and (3) to provide an algorithm for standardized mobility tests that can quickly and easily be performed in a private practice or on a hospital ward. MATERIALS AND METHODS: A Pubmed review of current literature on the topic as well as the personal experience and recommendations of the authors are presented. Assessments summarized: clock drawing test, stops walking when talking test, normal walking speed, timed up and go test, regular, as a dual task and imagined. RESULTS: It is recommended that at least two of the presented assessments should be performed at each clinical visit in all patients age 65 years or older. If one of the assessments presented provides abnormal results, patients should be referred to a gait specialist for an in-depth quantitative gait analysis. CONCLUSION: Assessments of functional mobility, fall risk and cognition should be an integral part of every comprehensive geriatric assessment. Quantitative gait analysis allows not only the early detection of gait deficits and fall risk, but also of cognitive deficits. Early detection allows for timely implementation of targeted interventions to improve gait and/or cognition.

Innovative diagnostic tools for early detection of Alzheimer's disease.

Current state-of-the-art diagnostic measures of Alzheimer's disease (AD) are invasive (cerebrospinal fluid analysis), expensive (neuroimaging) and time-consuming (neuropsychological assessment) and thus have limited accessibility as frontline screening and diagnostic tools for AD. Thus, there is an increasing need for additional noninvasive and/or cost-effective tools, allowing identification of subjects in the preclinical or early clinical stages of AD who could be suitable for further cognitive evaluation and dementia diagnostics. Implementation of such tests may facilitate early and potentially more effective therapeutic and preventative strategies for AD. Before applying them in clinical practice, these tools should be examined in ongoing large clinical trials. This review will summarize and highlight the most promising screening tools including neuropsychometric, clinical, blood, and neurophysiological tests.