Wearable sensors-based systems have emerged as a potential tool to continuously monitor Parkinson's Disease (PD) motor features in free-living environments.
To analyse the responsivity of wearable ...inertial sensor (WIS) measures (On/Off-Time, dyskinesia, freezing of gait (FoG) and gait parameters) after treatment adjustments. We also aim to study the ability of the sensor in the detection of MF, dyskinesia, FoG and the percentage of Off-Time, under ambulatory conditions of use.
We conducted an observational, open-label study. PD patients wore a validated WIS (STAT-ONTM) for one week (before treatment), and one week, three months after therapeutic changes. The patients were analyzed into two groups according to whether treatment changes had been indicated or not.
Thirty-nine PD patients were included in the study (PD duration 8 ± 3.5 years). Treatment changes were made in 29 patients (85%). When comparing the two groups (treatment intervention vs no intervention), the WIS detected significant changes in the mean percentage of Off-Time (p = 0.007), the mean percentage of On-Time (p = 0.002), the number of steps (p = 0.008) and the gait fluidity (p = 0.004). The mean percentage of Off-Time among the patients who decreased their Off-Time (79% of patients) was -7.54 ± 5.26. The mean percentage of On-Time among the patients that increased their On-Time (59% of patients) was 8.9 ± 6.46. The Spearman correlation between the mean fluidity of the stride and the UPDRS-III- Factor I was 0.6 (p = <0.001). The system detected motor fluctuations (MF) in thirty-seven patients (95%), whilst dyskinesia and FoG were detected in fifteen (41%), and nine PD patients (23%), respectively. However, the kappa agreement analysis between the UPDRS-IV/clinical interview and the sensor was 0.089 for MF, 0.318 for dyskinesia and 0.481 for FoG.
It's feasible to use this sensor for monitoring PD treatment under ambulatory conditions. This system could serve as a complementary tool to assess PD motor complications and treatment adjustments, although more studies are required.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Neuromelanin (NM) loss in substantia nigra pars compacta (SNc) and locus coeruleus (LC) reflects neuronal death in Parkinson's disease (PD). Since genetically-determined PD shows varied clinical ...expressivity, we wanted to accurately quantify and locate brainstem NM and iron, to discover whether specific MRI patterns are linked to Leucine-rich repeat kinase 2 G2019S PD (LRRK2-PD) or idiopathic Parkinson's disease (iPD). A 3D automated MRI atlas-based segmentation pipeline (3D-ABSP) for NM/iron-sensitive MRI images topographically characterized the SNc, LC, and red nucleus (RN) neuronal loss and calculated NM/iron contrast ratio (CR) and normalized volume (nVol). Left-side NM nVol was larger in all groups. PD had lower NM CR and nVol in ventral-caudal SNc, whereas iron increased in lateral, medial-rostral, and caudal SNc. The SNc NM CR reduction was associated with psychiatric symptoms. LC CR and nVol discriminated better among subgroups: LRRK2-PD had similar LC NM CR and nVol as that of controls, and larger LC NM nVol and RN iron CR than iPD. PD showed higher iron SNc nVol than controls, especially among LRRK2-PD. ROC analyses showed an AUC > 0.92 for most pairwise subgroup comparisons, with SNc NM being the best discriminator between HC and PD. NM measures maintained their discriminator power considering the subgroup of PD patients with less than 5 years of disease duration. The SNc iron CR and nVol increase was associated with longer disease duration in PD patients. The 3D-ABSP sensitively identified NM and iron MRI patterns strongly correlated with phenotypic PD features.
For specialists in charge of Parkinson's disease (PD), one of the most time-consuming tasks of the consultations is the assessment of symptoms and motor fluctuations. This task is complex and is ...usually based on the information provided by the patients themselves, which in most cases is complex and biased. In recent times, different tools have appeared on the market that allow automatic ambulatory monitoring. The MoMoPa-EC clinical trial (NCT04176302) investigates the effect of one of these tools-Sense4Care's STAT-ON-can have on routine clinical practice. In this sub-analysis the agreement between the Hauser diaries and the STAT-ON sensor is analyzed.
Eighty four patients from MoMoPa-EC cohort were included in this sub-analysis. The intraclass correlation coefficient was calculated between the patient diary entries and the sensor data.
The intraclass correlation coefficient of both methods was 0.57 (95% CI: 0.3-0.73) for the OFF time (%), 0.48 (95% CI: 0.17-0.68) for the time in ON (%), and 0.65 (95% CI%: 0.44-0.78) for the time with dyskinesias (%). Furthermore, the Spearman correlations with the UPDRS scale have been analyzed for different parameters of the two methods. The maximum correlation found was -0.63 (
< 0.001) between Mean Fluidity (one of the variables offered by the STAT-dON) and factor 1 of the UPDRS.
This sub-analysis shows a moderate concordance between the two tools, it is clearly appreciated that the correlation between the different UPDRS indices is better with the STAT-ON than with the Hauser diary.
https://clinicaltrials.gov/show/NCT04176302 (NCT04176302).
Abstract
Background
Neurodegenerative diseases are the most common age‐related pathologies, including Alzheimer’s disease (AD). Recent studies suggest that telomere attrition, the main trigger of ...cellular senescence, might contribute to brain dysfunction and neurodegeneration with age (Forero et al., 2016). Senescent brain cells have been found in AD patients (Musi et al., 2018), and studies in a transgenic mouse model of tauopathy have shown that the elimination of senescent cells led to an improvement in tau‐related neurodegeneration and cognitive decline (Bussian et al., 2018). However, little is known about the exact connection between senescent brain cells and neurodegenerative disorders on a cellular and molecular level. Here, we studied how brain senescence relates to the onset and progression of AD‐related tau pathology.
Method
We used a mouse model of senescence (TercKO), which is deficient for the RNA component of the telomerase, and presents telomere attrition and premature ageing with increasing generations (Blasco et al., 1997). We crossed it with the tauopathy mouse model Tau P301S (PS19), which carries the P301S mutant form of the human microtubule‐associated protein tau gene (MAPT), exhibiting tau pathology features observed in AD (Yoshiyama et al., 2007). By taking advantage of primary cultures, brain sections and brain extracts, and using biochemistry and molecular biology techniques, we examined the expression of tau neuropathological features in a senescent context. Furthermore, we evaluated the changes in classical and novel markers of senescence in a neurodegenerative context.
Result
We observed that telomere attrition induces several known senescence markers (i.e., senescence‐associated beta‐galactosidase or SA‐β‐gal activity, upregulation of interleukins IL‐1β and IL‐6, and cell cycle regulator p16) and this exacerbates tau phosphorylation in primary neurons and hippocampal tissue. Additionally, our results suggest that the senescent context might enhance tau‐induced neurodegeneration.
Conclusion
Our work indicates that senescence might be an upstream regulator of tau pathology, aggravating it and triggering tau‐related neurodegeneration. Our results further suggest that TercKO mice could be a useful animal model to study the pathological role of age‐associated brain senescence. Elucidating this process in more detail could lead to the identification of suitable intervention targets for AD treatment.
Neuroinflammation is a potential player in neurodegenerative conditions, particularly the aggressive ones, such as multiple system atrophy (MSA). Previous reports on cytokine levels in MSA using ...serum or cerebrospinal fluid (CSF) have been inconsistent, including small samples and a limited number of cytokines, often without comparison to Parkinson's disease (PD), a main MSA differential diagnosis.
Cross-sectional study of CSF levels of 38 cytokines using a multiplex assay in 73 participants: 39 MSA patients (19 with parkinsonian type MSAp, 20 with cerebellar type MSAc; 31 probable, 8 possible), 19 PD patients and 15 neurologically unimpaired controls. None of the participants was under non-steroidal anti-inflammatory drugs at the time of the lumbar puncture.
There were not significant differences in sex and age among participants. In global non-parametric comparisons FDR-corrected for multiple comparisons, CSF levels of 5 cytokines (FGF-2, IL-10, MCP-3, IL-12p40, MDC) differed among the three groups. In pair-wise FDR-corrected non-parametric comparisons 12 cytokines (FGF-2, eotaxin, fractalkine, IFN-α2, IL-10, MCP-3, IL-12p40, MDC, IL-17, IL-7, MIP-1β, TNF-α) were significantly higher in MSA vs. non-MSA cases (PD + controls pooled together). Of these, MCP-3 and MDC were the most significant ones, also differed in MSA vs. PD, and were significant MSA-predictors in binary logistic regression models and ROC curves adjusted for age. CSF levels of fractalkine and MIP-1α showed a strong and significant positive correlation with UMSARS-2 scores.
Increased CSF levels of cytokines such as MCP-3, MDC, fractalkine and MIP-1α deserve consideration as potential diagnostic or severity biomarkers of MSA.
•CSF levels of 12 cytokines were higher in MSA (n = 39) vs. PD + controls (n = 19 & 15).•Younger age and increasing CSF levels of MCP-3 and MDC were MSA predictors in adjusted models.•CSF levels of fractalkine and MIP-1α correlated with UMSARS-2 scores.•CSF levels of these cytokines might be diagnostic or severity MSA biomarkers.
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