Turning When Using Smartphone in Persons With and Those Without Neurologic Conditions: Observational Study

Background: Turning during walking is a relevant and common everyday movement and it depends on a correct top-down intersegmental coordination. This could be reduced in several conditions (en bloc turning), and an altered turning kinematics has been linked to increased risk of falls. Smartphone use has been associated with poorer balance and gait; however, its effect on turning-while-walking has not been investigated yet. This study explores turning intersegmental coordination during smartphone use in different age groups and neurologic conditions. Objective: This study aims to evaluate the effect of smartphone use on turning behavior in healthy individuals of different ages and those with various neurological diseases. Methods: Younger (aged 18-60 years) and older (aged >60 years) healthy individuals and those with Parkinson disease, multiple sclerosis, subacute stroke (<4 weeks), or lower-back pain performed turning-while-walking alone (single task [ST]) and while performing 2 different cognitive tasks of increasing complexity (dual task [DT]). The mobility task consisted of walking up and down a 5-m walkway at self-selected speed, thus including 180° turns. Cognitive tasks consisted of a simple reaction time test (simple DT [SDT]) and a numerical Stroop test (complex DT [CDT]). General (turn duration and the number of steps while turning), segmental (peak angular velocity), and intersegmental turning parameters (intersegmental turning onset latency and maximum intersegmental angle) were extracted for head, sternum, and pelvis using a motion capture system and a turning detection algorithm. Results: In total, 121 participants were enrolled. All participants, irrespective of age and neurologic disease, showed a reduced intersegmental turning onset latency and a reduced maximum intersegmental angle of both pelvis and sternum relative to head, thus indicating an en bloc turning behavior when using a smartphone. With regard to change from the ST to turning when using a smartphone, participants with Parkinson disease reduced their peak angular velocity the most, which was significantly different from lower-back pain relative to the head (P<.01). Participants with stroke showed en bloc turning already without smartphone use. Conclusions: Smartphone use during turning-while-walking may lead to en bloc turning and thus increase fall risk across age and neurologic disease groups. This behavior is probably particularly dangerous for those groups with the most pronounced changes in turning parameters during smartphone use and the highest fall risk, such as individuals with Parkinson disease. Moreover, the experimental paradigm presented here might be useful in differentiating individuals with lower-back pain without and those with early or prodromal Parkinson disease. In individuals with subacute stroke, en bloc turning could represent a compensative strategy to overcome the newly occurring mobility deficit. Considering the ubiquitous smartphone use in daily life, this study should stimulate future studies in the area of fall risk and neurological and orthopedic diseases

Gut Microbiome Signatures of Risk and Prodromal Markers of Parkinson Disease

Objective Alterations of the gut microbiome in Parkinson disease (PD) have been repeatedly demonstrated. However, little is known about whether such alterations precede disease onset and how they relate to risk and prodromal markers of PD. We investigated associations of these features with gut microbiome composition. Methods Established risk and prodromal markers of PD as well as factors related to diet/lifestyle, bowel function, and medication were studied in relation to bacterial alpha-/beta-diversity, enterotypes, and differential abundance in stool samples of 666 elderly TREND (Tubingen Evaluation of Risk Factors for Early Detection of Neurodegeneration) study participants. Results Among risk and prodromal markers, physical activity, occupational solvent exposure, and constipation showed associations with alpha-diversity. Physical activity, sex, constipation, possible rapid eye movement sleep behavior disorder (RBD), and smoking were associated with beta-diversity. Subthreshold parkinsonism and physical activity showed an interaction effect. Among other factors, age and urate-lowering medication were associated with alpha- and beta-diversity. Physical inactivity and constipation were highest in individuals with theFirmicutes-enriched enterotype. Constipation was lowest and subthreshold parkinsonism least frequent in individuals with thePrevotella-enriched enterotype. Differentially abundant taxa were linked to constipation, physical activity, possible RBD, smoking, and subthreshold parkinsonism. Substantia nigra hyperechogenicity, olfactory loss, depression, orthostatic hypotension, urinary/erectile dysfunction, PD family history, and the prodromal PD probability showed no significant microbiome associations. Interpretation Several risk and prodromal markers of PD are associated with gut microbiome composition. However, the impact of the gut microbiome on PD risk and potential microbiome-dependent subtypes in the prodrome of PD need further investigation based on prospective clinical and (multi)omics data in incident PD cases. ANN NEUROL 2020Peer reviewe

Adipose tissue ATGL modifies the cardiac lipidome in pressure-overload-induced left ventricular failure

Adipose tissue lipolysis occurs during the development of heart failure as a consequence of chronic adrenergic stimulation. However, the impact of enhanced adipose triacylglycerol hydrolysis mediated by adipose triglyceride lipase (ATGL) on cardiac function is unclear. To investigate the role of adipose tissue lipolysis during heart failure, we generated mice with tissue-specific deletion of ATGL (atATGL-KO). atATGL-KO mice were subjected to transverse aortic constriction (TAC) to induce pressure-mediated cardiac failure. The cardiac mouse lipidome and the human plasma lipidome from healthy controls (n = 10) and patients with systolic heart failure (HFrEF, n = 13) were analyzed by MS-based shotgun lipidomics. TAC-induced increases in left ventricular mass (LVM) and diastolic LV inner diameter were significantly attenuated in atATGL-KO mice compared to wild type (wt) -mice. More importantly, atATGL-KO mice were protected against TAC-induced systolic LV failure. Perturbation of lipolysis in the adipose tissue of atATGL-KO mice resulted in the prevention of the major cardiac lipidome changes observed after TAC in wt-mice. Profound changes occurred in the lipid class of phosphatidylethanolamines (PE) in which multiple PE-species were markedly induced in failing wt-hearts, which was attenuated in atATGL-KO hearts. Moreover, selected heart failure-induced PE species in mouse hearts were also induced in plasma samples from patients with chronic heart failure. TAC-induced cardiac PE induction resulted in decreased PC/PE-species ratios associated with increased apoptotic marker expression in failing wt-hearts, a process absent in atATGL-KO hearts. Perturbation of adipose tissue lipolysis by ATGL-deficiency ameliorated pressure-induced heart failure and the potentially deleterious cardiac lipidome changes that accompany this pathological process, namely the induction of specific PE species. Non-cardiac ATGL-mediated modulation of the cardiac lipidome may play an important role in the pathogenesis of chronic heart failure

Prodromal Markers in Parkinson's Disease:Limitations in Longitudinal Studies and Lessons Learned

A growing body of evidence supports a prodromal neurodegenerative process preceding the clinical onset of Parkinson's disease (PD). Studies have identified several different prodromal markers that may have the potential to predict the conversion from healthy to clinical PD but use considerably different approaches. We systematically reviewed 35 longitudinal studies reporting prodromal PD features and evaluated the methodological quality across 10 different predefined domains. We found limitations in the following domains: PD diagnosis (57% of studies), prodromal marker assessments (51%), temporal information on prodromal markers or PD diagnosis (34%), generalizability of results (17%), statistical methods (accounting for at least age as confounder; 17%), study design (14%), and sample size (9%). However, no limitations regarding drop-out (or bias investigation), or report of inclusion/exclusion criteria or prodromal marker associations were revealed. Lessons learned from these limitations and additional aspects of current prodromal marker studies in PD are discussed to provide a basis for the evaluation of findings and the improvement of future research in prodromal PD. The observed heterogeneity of studies, limitations and analyses might be addressed in future longitudinal studies using a, yet to be established, modular minimal set of assessments improving comparability of findings and enabling data sharing and combined analyses across studies

Insulin-Like Growth Factor 1 (IGF-1) in Parkinson's Disease: Potential as Trait-, Progression- and Prediction Marker and Confounding Factors

Introduction Biomarkers indicating trait, progression and prediction of pathology and symptoms in Parkinson's disease (PD) often lack specificity or reliability. Investigating biomarker variance between individuals and over time and the effect of confounding factors is essential for the evaluation of biomarkers in PD, such as insulin-like growth factor 1 (IGF-1). Materials and Methods IGF-1 serum levels were investigated in up to 8 biannual visits in 37 PD patients and 22 healthy controls (HC) in the longitudinal MODEP study. IGF-1 baseline levels and annual changes in IGF-1 were compared between PD patients and HC while accounting for baseline disease duration (19 early stage: 3.5 years; 18 moderate stage: >4 years), age, sex, body mass index (BMI) and common medical factors putatively modulating IGF-1. In addition, associations of baseline IGF-1 with annual changes of motor, cognitive and depressive symptoms and medication dose were investigated. Results PD patients in moderate (130±26 ng/mL; p = .004), but not early stages (115±19, p>.1), showed significantly increased baseline IGF-1 levels compared with HC (106±24 ng/mL; p = .017). Age had a significant negative correlation with IGF-1 levels in HC (r = -.47, p = .028) and no correlation in PD patients (r = -.06, p>.1). BMI was negatively correlated in the overall group (r = -.28, p = .034). The annual changes in IGF-1 did not differ significantly between groups and were not correlated with disease duration. Baseline IGF-1 levels were not associated with annual changes of clinical parameters. Discussion Elevated IGF-1 in serum might differentiate between patients in moderate PD stages and HC. However, the value of serum IGF-1 as a trait-, progression- and prediction marker in PD is limited as IGF-1 showed large inter- and intraindividual variability and may be modulated by several confounders

Corrigendum: White Matter Changes-Related Gait and Executive Function Deficits: Associations with Age and Parkinson's Disease.

[This corrects the article on p. 213 in vol. 9, PMID: 28713264.]

Progressive Gait Deficits in Parkinson’s Disease: A Wearable-Based Biannual 5-Year Prospective Study

Background: Gait changes occur during all Parkinson’s disease (PD) stages and wearable sensor-derived gait parameters may quantify PD progression. However, key aspects that may qualify quantitative gait parameters as progression markers in PD remain elusive.Objectives: Longitudinal changes in gait parameters from a lower-back sensor under convenient and challenging walking conditions in early- and mid-stage PD patients (E-PD, M-PD) compared to controls were investigated.Methods: Normal- and fast-pace parameters (step: number, time, velocity, variability) were assessed every 6 months for up to 5 years in 22 E-PD (<4 years baseline disease duration), 18 M-PD (>5 years) and 24 controls. Parameter trajectories and associations with MDS-UPDRS-III were tested using generalized estimating equations.Results: Normal-pace step number (annual change in E-PD: 2.1%, Time∗Group: p = 0.001) and step time variability (8.5%, p < 0.05) longitudinally increased in E-PD compared to controls (0.7%, -12%). For fast pace, no significant progression differences between groups were observed. Longitudinal changes in M-PD did not differ significantly from controls. MDS-UPDRS-III was largely associated with normal-pace parameters in M-PD.Conclusion: Wearables can quantify progressive gait deficits indicated by increasing step number and step time variability in E-PD. In M-PD, and for fast-pace, gait parameters possess limited potential as PD progression markers