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Introduction:Accurately assessing people’s gait, especially in real-world conditions and in case of impaired mobility, is still a challenge due to intrinsic and extrinsic factors resulting in gait complexity. To improve the estimation of gait-related digital mobility outcomes (DMOs) in real-world scenarios, this study presents a wearable multi-sensor system (INDIP), integrating complementary sensing approaches (two plantar pressure insoles, three inertial units and two distance sensors). Methods:The INDIP technical validity was assessed against stereophotogrammetry during a laboratory experimental protocol comprising structured tests (including continuous curvilinear and rectilinear walking and steps) and a simulation of daily-life activities (including intermittent gait and short walking bouts). To evaluate its performance on various gait patterns, data were collected on 128 participants from seven cohorts: healthy young and older adults, patients with Parkinson’s disease, multiple sclerosis, chronic obstructive pulmonary disease, congestive heart failure, and proximal femur fracture. Moreover, INDIP usability was evaluated by recording 2.5-h of real-world unsupervised activity. Results and discussion:Excellent absolute agreement (ICC >0.95) and very limited mean absolute errors were observed for all cohorts and digital mobility outcomes (cadence ≤0.61 steps/min, stride length ≤0.02m, walking speed ≤0.02m/s) in the structured tests. Larger, but limited, errors were observed during the daily-life simulation (cadence 2.72–4.87 steps/min, stride length 0.04–0.06m, walking speed 0.03–0.05m/s). Neither major technical nor usability issues were declared during the 2.5-h acquisitions. Therefore, the INDIP system can be considered a valid and feasible solution to collect reference data for analyzing gait in real-world conditions.

Background: Common genetic variance in apolipoprotein E (APOE), β‐glucocerebrosidase (GBA), microtubule‐associated protein tau (MAPT), and α‐synuclein (SNCA) has been linked to cognitive decline in Parkinson’s disease (PD), although studies have yielded mixed results. Objectives: To evaluate the effect of genetic variants in APOE, GBA, MAPT, and SNCA on cognitive decline and risk of dementia in a pooled analysis of six longitudinal, non‐selective, population‐based cohorts of newly diagnosed PD patients. Methods: 1002 PD patients, followed for up to 10 years (median 7.2 years), were genotyped for at least one of APOE ‐ε4, GBA mutations, MAPT H1/H2, or SNCA rs356219. We evaluated the effect of genotype on the rate of cognitive decline (Mini‐Mental State Examanation, MMSE) using linear mixed models and the development of dementia (diagnosed using standardized criteria) using Cox regression; multiple comparisons were accounted for using Benjamini−Hochberg corrections. Results: Carriers of APOE‐ε4 (n = 281, 29.7%) and GBA mutations (n = 100, 10.3%) had faster cognitive decline and were at higher risk of progression to dementia (APOE‐ε4, HR 3.57, P < 0.001; GBA mutations, HR 1.76, P = 0.001) than non‐carriers. The risk of cognitive decline and dementia (HR 5.19, P < 0.001) was further increased in carriers of both risk genotypes (n = 23). No significant effects were observed for MAPT or SNCA rs356219. Conclusions: GBA and APOE genotyping could improve the prediction of cognitive decline in PD, which is important to inform the clinical trial selection and potentially to enable personalized treatment © 2022 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society

Funder: GE Healthcare; Id: http://dx.doi.org/10.13039/100006775, Funder: Alzheimer's Research UK; Id: http://dx.doi.org/10.13039/501100002283, Funder: NIHR Newcastle Biomedical Research Centre; Id: http://dx.doi.org/10.13039/501100012295, Objectives: Autonomic symptoms are a common feature of the synucleinopathies, and may be a distinguishing feature of prodromal Lewy body disease. We aimed to assess whether the cognitive prodrome of dementia with Lewy bodies, mild cognitive impairment (MCI) with Lewy bodies (MCI‐LB), would have more severe reported autonomic symptoms than cognitively healthy older adults, with MCI due to Alzheimer's disease (MCI‐AD) also included for comparison. We also aimed to assess the utility of an autonomic symptom scale in differentiating MCI‐LB from MCI‐AD. Methods: Ninety‐three individuals with MCI and 33 healthy controls were assessed with the Composite Autonomic Symptom Score 31‐item scale (COMPASS). Mild cognitive impairment patients also underwent detailed clinical assessment and differential classification of MCI‐AD or MCI‐LB according to current consensus criteria. Differences in overall COMPASS score and individual symptom sub‐scales were assessed, controlling for age. Results: Age‐adjusted severity of overall autonomic symptomatology was greater in MCI‐LB (Ratio = 2.01, 95% CI: 1.37–2.96), with higher orthostatic intolerance and urinary symptom severity than controls, and greater risk of gastrointestinal and secretomotor symptoms. MCI‐AD did not have significantly higher autonomic symptom severity than controls overall. A cut‐off of 4/5 on the COMPASS was sensitive to MCI‐LB (92%) but not specific to this (42% specificity vs. MCI‐AD and 52% vs. healthy controls). Conclusions: Mild cognitive impairment with Lewy bodies had greater autonomic symptom severity than normal ageing and MCI‐AD, but such autonomic symptoms are not a specific finding. The COMPASS‐31 may therefore have value as a sensitive screening test for early‐stage Lewy body disease.

Funder: Academy of Medical Sciences; Id: http://dx.doi.org/10.13039/501100000691, Funder: American Parkinson Disease Association Center for Advanced Parkinson Research, Funder: BMA Doris Hillier award, Funder: Bupa Foundation; Id: http://dx.doi.org/10.13039/501100000355, Funder: Cure Parkinson's Trust, Funder: Erling‐Persson Foundation, Funder: European Research Council; Id: http://dx.doi.org/10.13039/501100000781, Funder: Hjärnfonden; Id: http://dx.doi.org/10.13039/501100003792, Funder: John and Lucille Van Geest Foundation; Id: http://dx.doi.org/10.13039/501100020410, Funder: Kempestiftelserna; Id: http://dx.doi.org/10.13039/501100007067, Funder: Knut och Alice Wallenbergs Stiftelse; Id: http://dx.doi.org/10.13039/501100004063, Funder: Konung Gustaf V:s och Drottning Victorias Frimurarestiftelse; Id: http://dx.doi.org/10.13039/501100006129, Funder: Lockhart Parkinson's Disease Research Fund, Funder: Medical Research Council; Id: http://dx.doi.org/10.13039/501100007155, Funder: Medicinska Forskningdet, Funder: NIHR Newcastle Biomedical Research Unit and Centre, Funder: NHS Grampian endowments, Funder: Norwegian Health Association; Id: http://dx.doi.org/10.13039/501100013263, Funder: Norwegian Parkinson's Research Foundation, Funder: Patrick Berthoud Trust, Funder: Rebergs Legacy, Funder: RS Macdonald Trust, Funder: SPRING; Id: http://dx.doi.org/10.13039/100001869, Funder: Swedish Parkinson Foundation, Funder: Umeå Universitet; Id: http://dx.doi.org/10.13039/501100004885, Funder: Västerbotten Läns Landsting; Id: http://dx.doi.org/10.13039/501100002960, Funder: Wellcome Trust; Id: http://dx.doi.org/10.13039/100010269, Background: Common genetic variance in apolipoprotein E (APOE), β‐glucocerebrosidase (GBA), microtubule‐associated protein tau (MAPT), and α‐synuclein (SNCA) has been linked to cognitive decline in Parkinson’s disease (PD), although studies have yielded mixed results. Objectives: To evaluate the effect of genetic variants in APOE, GBA, MAPT, and SNCA on cognitive decline and risk of dementia in a pooled analysis of six longitudinal, non‐selective, population‐based cohorts of newly diagnosed PD patients. Methods: 1002 PD patients, followed for up to 10 years (median 7.2 years), were genotyped for at least one of APOE ‐ε4, GBA mutations, MAPT H1/H2, or SNCA rs356219. We evaluated the effect of genotype on the rate of cognitive decline (Mini‐Mental State Examanation, MMSE) using linear mixed models and the development of dementia (diagnosed using standardized criteria) using Cox regression; multiple comparisons were accounted for using Benjamini−Hochberg corrections. Results: Carriers of APOE‐ε4 (n = 281, 29.7%) and GBA mutations (n = 100, 10.3%) had faster cognitive decline and were at higher risk of progression to dementia (APOE‐ε4, HR 3.57, P < 0.001; GBA mutations, HR 1.76, P = 0.001) than non‐carriers. The risk of cognitive decline and dementia (HR 5.19, P < 0.001) was further increased in carriers of both risk genotypes (n = 23). No significant effects were observed for MAPT or SNCA rs356219. Conclusions: GBA and APOE genotyping could improve the prediction of cognitive decline in PD, which is important to inform the clinical trial selection and potentially to enable personalized treatment © 2022 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society