Coronavirus disease 2019 (COVID-19) pandemic is quickly spreading, putting under heavy stress health systems worldwide and especially Intensive Care Units (ICU). Rehabilitation Units have a crucial ...role in reducing disability in order to reintroduce patients in the community.
The aim of this study is to characterize pulmonary function and disability status and to propose an early rehabilitation protocol in a cohort of post-acute COVID-19 patients admitted to an Italian Rehabilitation Unit.
Cross-sectional observational study.
Inpatients Rehabilitation Unit.
Post-acute COVID-19 patients.
Demographic, anamnestic and clinical characteristics, laboratory exams and medical imaging findings were collected for the entire cohort. Outcome measures evaluated at the admission in Rehabilitation Unit were: type of respiratory supports needed, fraction of inspired oxygen (FiO2), partial pressure of oxygen (PaO2), FiO2/PaO2, Barthel Index (BI), modified Medical Research Council (mMRC) Dyspnoea Scale, and 6-Minute Walking Test (6-MWT). Furthermore, we proposed an early rehabilitation protocol for COVID-19 patients based on baseline FiO2.
We included 32 post-acute COVID-19 patients (22 male and 10 female), mean aged 72.6±10.9 years. BI was 45.2±27.6, with patients in need of higher FiO2 (≥40%) showing lower values: 39.6±25.7 vs. 53.3±29.3. All patients had grade 4 or 5 on the mMRC Dyspnea Scale. Only 14 COVID-19 patients were able to walk (43.7%). 6-MWT was feasible in 6 (18.8%) patients with a mean distance of 45.0±100.6 meters.
Taken together, our findings suggest that post-acute COVID-19 patients suffered from dyspnea and shortness of breath even for minimal activities, with a resulting severe disability, and only a few of them were able to perform 6-MWT with poor results. An early rehabilitation protocol was proposed according to the baseline conditions of the patients.
This study could provide an accurate description of COVID-19 sub-acute patients admitted to a Rehabilitation Unit along with a proposal of treatment to help physicians to tailor the best possible rehabilitative treatment.
Confabulations, also known as false memories, have been associated with various diseases involving mainly the frontal areas, such as Wernicke–Korsakoff syndrome or frontal epilepsy. The ...neuropsychological dysfunctions underlying mechanisms of confabulation are not well known. We describe two patients with memory impairment and confabulations at the onset speculating about neuropsychological correlates of confabulations and self-awareness. Both patients, a 77-year-old woman and a 57-years-old man, exhibited confabulations as first symptom of cognitive decline. She later developed memory impairment without awareness of her memory deficits and her cognitive and imaging profile suggested an amnesic mild cognitive impairment due to Alzheimer’s disease (AD). Unlike her, he developed a prevalent involvement of frontal functions despite a clear consciousness of his cognitive deficits. However, the clinical diagnostic hypothesis of behavioral variant of frontotemporal dementia was not supported by imaging findings, which suggested AD. Both patients underwent neuropsychological evaluation including the Confabulation Battery. Despite that the exact anatomical correlation of confabulations is still not defined, imaging data shown by our patients is consistent with recent theories according to which at the origin of confabulatory tendency in AD there is an impairment of the connections between crucial hubs in frontal and mediotemporal areas, mainly involving the right hemisphere. Besides, it would be reasonable to hypothesize that self-awareness and confabulations should not be considered as necessarily associated dimensions.
Neurodegenerative disorders (NDs) are characterized by abnormal accumulation/misfolding of specific proteins, primarily α-synuclein (α-syn), β-amyloid
(Aβ
) and tau, in both brain and peripheral ...tissues. In addition to oligomers, the role of the interactions of α-syn with Aβ or tau has gradually emerged. Nevertheless, despite intensive research, NDs have no accepted peripheral markers for biochemical diagnosis. In this respect, Red Blood Cells (RBCs) are emerging as a valid peripheral model for the study of aging-related pathologies. Herein, a small cohort (
= 28) of patients affected by Parkinson's disease (PD) and age-matched controls were enrolled to detect the content of α-syn (total and oligomeric), Aβ
and tau (total and phosphorylated) in RBCs. Moreover, the presence of α-syn association with tau and Aβ
was explored by co-immunoprecipitation/western blotting in the same cells, and quantitatively confirmed by immunoenzymatic assays. For the first time, PD patients were demonstrated to exhibit α-syn heterocomplexes with Aβ
and tau in peripheral tissues; interestingly, α-syn-Aβ
concentrations were increased in PD subjects with respect to healthy controls (HC), and directly correlated with disease severity and motor deficits. Moreover, total-α-syn levels were decreased in PD subjects and inversely related to their motor deficits. Finally, an increase of oligomeric-α-syn and phosphorylated-tau was observed in RBCs of the enrolled patients. The combination of three parameters (total-α-syn, phosphorylated-tau and α-syn-Aβ
concentrations) provided the best fitting predictive index for discriminating PD patients from controls. Nevertheless further investigations should be required, overall, these data suggest α-syn hetero-aggregates in RBCs as a putative tool for the diagnosis of PD.
The impact of reperfusion therapies on cognition has been poorly explored and little knowledge exists. We explored the influence of endovascular treatment (EVT) on cognitive outcome in patients with ...anterior circulation ischemic stroke. Patients presenting with ischemic stroke due to anterior large vessel occlusion who underwent intravenous thrombolysis (IVT) alone or EVT plus IVT were recruited. Cognitive abilities were evaluated at 6 months from stroke through a neuropsychological test battery. A total of 88 patients with a mean age of 66.3 ± 12.9 years were included, of which 38 treated with IVT alone and 50 with IVT plus EVT. Compared to patients treated with IVT alone, patients who received EVT plus IVT performed significantly better at the neuropsychological tests exploring executive functions, attention, abstract reasoning, visuospatial ability, visual and verbal and memory. At multivariable regression analysis, the EVT was independently associated with the 6-month cognitive performance after the adjustment for age, sex, admission National Institutes of Health Stroke Scale score, systolic blood pressure, glucose level, Alberta Stroke Program Early CT score, side of stroke, site of occlusion, and Back Depression Inventory score Stroop Test Word Reading:
β = 13.99, 95% confidence interval (CI) 8.47-19.50, p < 0.001; Stroop Test Colour Naming:
β = 6.63, 95% CI 2.46-10.81, p = 0.002; Trail Making Test-A:
β = - 92.98, 95% CI - 153.76 to - 32.20, p = 0.003; Trail Making Test-B:
β = - 181.12, 95% CI - 266.09 to - 96.15; p < 0.001; Digit Span Test Forward:
β = 1.44, 95% CI 0.77-2.10, p < 0.001; Digit Span Test Backward:
β = 1.10, 95% CI 0.42-1.77, p = 0.002; Coloured Progressive Matrices:
β = 5.82, 95% CI 2.71-8.93, p < 0.001; Rey Complex Figure Test-Copy:
β = 6.02, 95% CI 2.74-9.30, p < 0.001; Rey Complex Figure Test-Immediate recall:
β = 6.00, 95% CI 2.34-9.66, p = 0.002; Rey Complex Figure Test-Delayed recall:
β = 5.73, 95% CI 1.95-9.51, p = 0.003; Rey Auditory Verbal Learning Test-Immediate recall:
β = 12.60, 95% CI 6.69-18.52, p < 0.001; Rey Auditory Verbal Learning Test-Delayed recall:
β = 1.85, 95% CI 0.24-3.45, p = 0.025. Patients treated with EVT plus IVT had better cognitive performance than patients treated with IVT alone at 6 months from anterior circulation ischemic stroke.
Altered mitochondrial DNA (mtDNA) methylation has been detected in several human pathologies, although little attention has been given to neurodegenerative diseases. Recently, altered methylation ...levels of the mitochondrial displacement loop (D-loop) region, which regulates mtDNA replication, were observed in peripheral blood cells of Alzheimer’s disease and amyotrophic lateral sclerosis patients. However, nothing is yet known about D-loop region methylation levels in peripheral blood of Parkinson’s disease (PD) patients. In the current study, we investigated D-loop methylation levels and mtDNA copy number in peripheral blood of 30 PD patients and 30 age- and sex-matched control subjects. DNA methylation analyses have been performed by means of methylation-sensitive high-resolution melting (MS-HRM) and pyrosequencing techniques, while mtDNA copy number was analyzed by quantitative PCR. MS-HRM and pyrosequencing analyses provided very similar D-loop methylation levels in PD patients and control subjects, and no differences between the two groups have been observed. Treatment with L-dopa and duration of the disease had no effect on D-loop methylation levels in PD patients. Additionally, mtDNA copy number did not differ between PD patients and control subjects. Current results suggest that D-loop methylation levels are not altered in peripheral blood of PD patients nor influenced by dopaminergic treatment.
: Tau protein misfolding and accumulation in toxic species is a critical pathophysiological process of Alzheimer's disease (AD) and other neurodegenerative disorders (NDDs). Tau biomarkers, namely ...cerebrospinal fluid (CSF) total-tau (t-tau), 181-phosphorylated tau (p-tau), and tau-PET tracers, have been recently embedded in the diagnostic criteria for AD. Nevertheless, the role of tau as a diagnostic and prognostic biomarker for other NDDs remains controversial.
: We performed a systematical PubMed-based review of the most recent advances in tau-related biomarkers for NDDs. We focused on papers published from 2015 to 2020 assessing the diagnostic or prognostic value of each biomarker.
: The assessment of tau biomarkers in alternative easily accessible matrices, through the development of ultrasensitive techniques, represents the most significant perspective for AD-biomarker research. In NDDs, novel tau isoforms (e.g. p-tau217) or proteolytic fragments (e.g. N-terminal fragments) may represent candidate diagnostic and prognostic biomarkers and may help monitoring disease progression. Protein misfolding amplification assays, allowing the identification of different tau strains (e.g. 3 R-
. 4 R-tau) in CSF, may constitute a breakthrough for the in vivo stratification of NDDs. Tau-PET may help tracking the spatial-temporal evolution of tau pathophysiology in AD but its application outside the AD-spectrum deserves further studies.
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.
In the present study, we aimed to better investigate attention system profile of Parkinson's disease-Mild Cognitive Impairment (PD-MCI) patients and to determine if specific attentional deficits are ...associated with 123I-FP-CIT SPECT.
A total of 44 de novo drug-naïve PD patients (27) with normal cognition (PD-NC) and 17 with MCI (PD-MCI), 23 MCI patients and 23 individuals with subjective cognitive impairment (SCI) were recruited at the Clinical Neurology Unit of Santa Chiara hospital (Pisa University Medical School, Italy). They were assessed by a wide neuropsychological battery, including Visual Search Test (VST) measuring selective attention. Performances among groups were compared by non-parametric tests (i.e., Kruskal-Wallis and Mann-Whitney, Bonferroni corrected). Further, Spearman's rank correlations were performed to explore the association between neuropsychological variables and 123I-FP-CIT SPECT data in PD subgroup.
PD-MCI patients performed worse on VST than patients with PD-NC (
= 0.002), patients with MCI and individuals with SCI (
< 0.001). The performance of PD-MCI patients on VST significantly correlated with caudate nucleus 123I-FP-CIT SPECT uptake (rho = 0.582,
< 0.05), whereas a negative correlation between such test and 123I-FP-CIT SPECT uptake in the left putamen (rho = -0.529,
< 0.05) was found in PD-NC patients.
We suggest that selective attention deficit might be a trigger of cognitive decay in de novo PD-MCI patients. The VST should be routinely used to detect attentional deficits in hospital clinical practice, in the light of its closely association with dopamine depletion of basal ganglia in mildly impaired PD patients.
A healthy lifestyle plays a strategic role in the prevention of BC. The aim of our prospective study is to evaluate the effects of a lifestyle interventions program based on special exercise and ...nutrition education on weight, psycho-physical well-being, blood lipid and hormonal profile among BC patients who underwent primary surgery. From January 2014 to March 2017, a multidisciplinary group of oncologists, dieticians, physiatrists and an exercise specialist evaluated 98 adult BC female patients at baseline and at different time points. The patients had at least one of the following risk factors: BMI ≥ 25 kg/m2, high testosterone levels, high serum insulin levels or diagnosis of MS. Statistically significant differences are shown in terms of BMI variation with the lifestyle interventions program, as well as in waist circumference and blood glucose, insulin and testosterone levels. Moreover, a statistically significant difference was reported in variations of total Hospital Anxiety and Depression Scale (HADS) score, in the anxiety HADS score and improvement in joint pain. Our results suggested that promoting a healthy lifestyle in clinical practice reduces risk factors involved in BC recurrence and ensures psycho-physical well-being.
α-syn aggregates represent the pathological hallmark of synucleinopathies as well as a frequent copathology (almost 1/3 of cases) in AD. Recent research indicates a potential role of α-syn species, ...measured in CSF with conventional analytical techniques, in the differential diagnosis between AD and synucleinopathies (such as DLB). Pioneering studies report the detection of α-syn in blood, however, conclusive investigations are controversial. Ultrasensitive seed amplification techniques, enabling the selective quantification of α-syn seeds, may represent an effective solution to identify the α-syn component in AD and facilitate a biomarker-guided stratification.
We performed a PubMed-based review of the latest findings on α-syn-related biomarkers for AD, focusing on bodily fluids. A dissertation on the role of ultrasensitive seed amplification assays, detecting α-syn seeds from different biological samples, was conducted.
α-syn may contribute to progressive AD neurodegeneration through cross-seeding especially with tau protein. Ultrasensitive seed amplification techniques may support a biomarker-drug co-development pathway and may be a pathophysiological candidate biomarker for the evolving ATX(N) system to classify AD and the spectrum of primary NDDs. This would contribute to a precise approach to AD, aimed at implementing disease-modifying treatments.