A major goal of current clinical research in Parkinson's disease (PD) is the validation and standardization of biomarkers enabling early diagnosis, predicting outcomes, understanding PD ...pathophysiology, and demonstrating target engagement in clinical trials. Molecular imaging with specific dopamine-related tracers offers a practical indirect imaging biomarker of PD, serving as a powerful tool to assess the status of presynaptic nigrostriatal terminals. In this review we provide an update on the dopamine transporter (DAT) imaging in PD and translate recent findings to potentially valuable clinical practice applications. The role of DAT imaging as diagnostic, preclinical and predictive biomarker is discussed, especially in view of recent evidence questioning the incontrovertible correlation between striatal DAT binding and nigral cell or axon counts.
Background
Functional connectivity (FC) studies showed that pharmaco-resistant mesial temporal lobe epilepsy (MTLE) affects not only the limbic system, but also several extra-limbic regions, ...including areas belonging to resting state networks. Less is known about FC in subjects with benign MTLE (i.e., sensitive to antiseizure medication, bMTLE).
Aim and methods
We evaluated FC of hippocampus and amygdala in subjects with bMTLE, distinguished based on the epileptic focus lateralization. We enrolled 19 patients (10 with left and 9 with right bMTLE) and 10 age-matched healthy subjects. Connectivity was investigated at rest by using a seed-based regression analyses approach with four regions of interest (left and right hippocampus, left and right amygdala). Patients were also tested with a neuropsychological battery and their scores were correlated with fMRI data.
Results and conclusions
Our study documented an asymmetrical disruption of FC in bMTLE, in relation to the side of the focus. Right subjects only exhibited limited altered connections, while left subjects—who performed worse in verbal memory tests—showed a wide bilateral hypoconnectivity of hippocampus and amygdala with areas belonging to language and memory network. The strength of FC between left limbic areas and language and memory network correlated with better performances in verbal memory tests. Moreover, we observed an increased FC with areas of default mode network, more pronounced in left subjects, a possible attempt to compensate cognitive deficit but without effectiveness.
We believe that these findings could help to better characterize bMTLE, in which a dysfunction of limbic connectivity is detectable despite well-controlled epilepsy.
Postural abnormalities in Parkinson's disease (PD) form a spectrum of functional trunk misalignment, ranging from a "typical" parkinsonian stooped posture to progressively greater degrees of spine ...deviation.
To analyze the association between degree of postural abnormalities and disability and to determine cut-off values of trunk bending associated with limitations in activities of daily living (ADLs), motor impairment, falls, and back pain.
The study population was 283 PD patients with ≥5° of forward trunk bending (FTB), lateral trunk bending (LTB) or forward neck bending (FNB). The degrees were calculated using a wall goniometer (WG) and software-based measurements (SBM). Logistic regression models were used to identify the degree of bending associated with moderate/severe limitation in ADLs (Movement Disorders Society Unified PD Rating Scale MDS-UPDRS part II ≥17), moderate/severe motor impairment (MDS-UPDRS part III ≥33), history of falls (≥1), and moderate/severe back pain intensity (numeric rating scale ≥4). The optimal cut-off was identified using receiver operating characteristic (ROC) curves.
We found significant associations between modified Hoehn & Yahr stage, disease duration, sex, and limitation in ADLs, motor impairment, back pain intensity, and history of falls. Degree of trunk bending was associated only with motor impairment in LTB (odds ratio OR 1.12; 95% confidence interval CI, 1.03-1.22). ROC curves showed that patients with LTB of 10.5° (SBM, AUC 0.626) may have moderate/severe motor impairment.
The severity of trunk misalignment does not fully explain limitation in ADLs, motor impairment, falls, and back pain. Multiple factors possibly related to an aggressive PD phenotype may account for disability in PD patients with FTB, LTB, and FNB.
ABSTRACT
Introduction
The overall frequency of postural abnormalities (PA) in Parkinson's disease (PD) is unknown. We evaluated the overall prevalence of PA and assessed the association with ...demographic and clinical variables.
Methods
For this multicenter, cross‐sectional study, consecutive PD outpatients attending 7 tertiary Italian centers were enrolled. Patients were evaluated and compared for the presence of isolated PA such as camptocormia, Pisa syndrome, and anterocollis and for combined forms (ie, camptocormia + Pisa syndrome) together with demographic and clinical variables.
Results
Of the total 811 PD patients enrolled, 174 (21.5%; 95% confidence interval CI, 18.6%–24.3%) presented PA, 144 of which had isolated PA and 30 had combined PA. The prevalence of camptocormia was 11.2% (95% CI, 9%–13.3%), Pisa syndrome 8% (95% CI, 6.2%–9.9%), and anterocollis 6.5% (95% CI, 4.9%–8.3%). Patients with PA were more often male and older with longer disease duration, more advanced disease stage, more severe PD symptoms, a bradykinetic/rigid phenotype, and poorer quality of life. They were initially treated with levodopa, and more likely to be treated with a combination of levodopa and dopamine agonist, took a higher daily levodopa equivalent daily dose, and had more comorbidities. Falls and back pain were more frequent in PD patients with PA than in those without PA. Multiple logistic regression models confirmed an association between PA and male gender, older age, Hoehn and Yahr stage, and total Unified Parkinson's Disease Rating Scale score.
Conclusions
PA are frequent and disabling complications in PD, especially in the advanced disease stages.
The diagnosis of neurodegenerative diseases (NDDs) represents an increasing social burden, with the unsolved issue of disease-modifying therapies (DMTs). The failure of clinical trials treating ...Alzheimer's Disease (AD) so far highlighted the need for a different approach in drug design and patient selection. Identifying subjects in the prodromal or early symptomatic phase is critical to slow down neurodegeneration, but the implementation of screening programs with this aim will have an ethical and social aftermath. Novel minimally invasive candidate biomarkers (derived from blood, saliva, olfactory brush) or classical cerebrospinal fluid (CSF) biomarkers have been developed in research settings to stratify patients with NDDs. Misfolded protein accumulation, neuroinflammation, and synaptic loss are the pathophysiological hallmarks detected by these biomarkers to refine diagnosis, prognosis, and target engagement of drugs in clinical trials. We reviewed fluid biomarkers of NDDs, considering their potential role as screening, diagnostic, or prognostic tool, and their present-day use in clinical trials (phase II and III). A special focus will be dedicated to novel techniques for the detection of misfolded proteins. Eventually, an applicative diagnostic algorithm will be proposed to translate the research data in clinical practice and select prodromal or early patients to be enrolled in the appropriate DMTs trials for NDDs.
Background
If Parkinson’s Disease (PD) may represent a risk factor for Coronavirus disease 2019 (COVID-19) is debated and there are few data on the direct and indirect effects of this pandemic in PD ...patients.
Objective
In the current study we evaluated the prevalence, mortality and case-fatality of COVID-19 in a PD cohort, also exploring possible risk factors. We also aimed to investigate the effect of lockdown on motor/non-motor symptoms in PD patients as well as their acceptability/accessibility to telemedicine.
Method
A case-controlled survey about COVID-19 and other clinical features in PD patients living in Tuscany was conducted. In non-COVID-19 PD patients motor/non-motor symptoms subjective worsening during the lockdown as well as feasibility of telemedicine were explored.
Results
Out of 740 PD patients interviewed, 7 (0.9%) were affected by COVID-19, with 0.13% mortality and 14% case-fatality. COVID-19 PD patients presented a higher presence of hypertension (
p
< 0.001) and diabetes (
p
= 0.049) compared to non-COVID-19. In non-COVID-19 PD population (
n
= 733) about 70% did not experience a subjective worsening of motor symptoms or mood, anxiety or insomnia. In our population 75.2% of patients was favorable to use technology to perform scheduled visits, however facilities for telemedicine were available only for 51.2% of cases.
Conclusion
A higher prevalence of COVID-19 respect to prevalence in Tuscany and Italy was found in the PD population. Hypertension and diabetes, as for general population, were identified as risk factors for COVID-19 in PD. PD patients did not experience a subjective worsening of symptoms during lockdown period and they were also favorable to telemedicine, albeit we reported a reduced availability to perform it.
It has been speculated that stains are neuroprotective and are associated with a reduced risk of Parkinson's disease (PD), but only a few studies have investigated the influence of statins on the ...progression of PD.
To evaluate whether long-term statin use may affect motor progression in a large cohort of de novo patients with PD.
We conducted a 4-year retrospective observational cohort study to assess patients with PD. The patients were consecutively recruited from a single tertiary center between January 2015 and January 2017. Information on motor function was obtained using the MDS-Unified Parkinson Disease Rating Scale (UPDRS)-III and all subjects were extensively characterized, including information about lifestyle habits, cardiovascular risk factors and cholesterol blood levels.
Of the 181 participants included in the study, 104 patients were evaluated for eligibility (42 patients were exposed to statin therapies and 62 were not treated with statins). They presented similar scores in UPDRS III at baseline but the statin users had a lower motor impairment at 4 years compared to non-user PD patients. Additionally, statin treatment resulted in slower progression of the rigidity score of UPDRS over 4 years. No other significant differences were observed between PD patients with and without statins.
Early PD patients with long-term statin usage showed lower motor deterioration after 4 years of disease duration compared with patients not taking statins at diagnosis, suggesting a possible influence of statins on disease progression in PD. Further investigation is warranted to understand the potential beneficial effects of statin treatment on clinical symptoms in PD.
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