Background: Knowledge about sleep complaints of caregivers of patients with Alzheimer's disease (AD) and Parkinson's disease (PD) is limited, and we lack information about the relationship between ...caregivers’ sleep problems and their quality of life (QoL).
Methods: We evaluated subjective sleep quality and its relationship to QoL in a group of 80 caregivers of patients with AD (ADCG, n = 40) and PD (PDCG, n = 40), and in 150 controls. Information about night-time complaints was collected using the Pittsburgh Sleep Quality Index (PSQI). QoL was measured using the McGill QoL Questionnaire.
Results: Eighteen ADCG (45%), 22 PDCG (55%), and 45 (30%) controls reported poor sleep quality. Mean global PSQI score of PDCG (6.25 ± 3.9) was not significantly different from that of ADCG (5.8 ± 3.5; p = 0.67). However, both PDCG and ADCG scored significantly higher than control group (4.3 ± 3.1; p < 0.01). ADCG frequently reported difficulties falling asleep (72.5%) and disturbed sleep (100%). PDCG reported reduced subjective sleep quality (80%) and increased sleep disturbances (100%). Poor sleep quality was associated with depressive symptoms and correlated with QoL in caregivers of both groups, particularly the psychological symptoms domain.
Conclusions: Among caregivers of patients with AD and PD, poor sleep quality is frequent and significantly linked to QoL and depressive symptoms. Identifying the nature of sleep disturbances not only in patients but also in their caregivers is important as appropriate treatment may lead to a better management of the needs of families coping with these patients.
IMPORTANCE: The evaluation of therapeutic choices is needed after 24 doses of natalizumab in patients with multiple sclerosis (MS). OBJECTIVE: To evaluate the effect of therapeutic choices on the ...mean annualized relapse rate and on magnetic resonance imaging MS activity after 24 doses of natalizumab in patients with relapsing-remitting MS. DESIGN, SETTING, AND PARTICIPANTS: The TY-STOP study, which recruited participants between October 22, 2010, and October 22, 2012, at 8 Italian MS centers (secondary care outpatient clinics) among 124 adult patients who demonstrated no clinical or magnetic resonance imaging MS activity after 24 doses of natalizumab. INTERVENTIONS: Natalizumab, no treatment, interferon beta, glatiramer acetate, or fingolimod. MAIN OUTCOMES AND MEASURES: The primary end point was the mean annualized relapse rate. Statistical analyses were performed in 124 patients with complete follow-up data among 130 patients who were recruited and stratified into study groups. In the intent-to-treat group, the decision was made to continue or interrupt natalizumab after 24 doses. In the as-treated group, natalizumab continuers received natalizumab, natalizumab switchers changed to different therapies, and natalizumab quitters discontinued natalizumab during the study year. RESULTS: No significant differences in demographic or baseline clinical characteristics were found among the study participants. In the intent-to-treat group (n = 124), clinical (P = .004) and radiologic (P = .02) MS activity was significantly lower in patients continuing natalizumab (n = 43) than in patients interrupting natalizumab (n = 81), with a protective effect of natalizumab continuation on both outcomes (odds ratio OR, 0.33; 95% CI, 0.15-0.70 for clinical activity and OR, 0.35; 95% CI, 0.15-0.79 for radiologic activity). In the as-treated group (n = 124), clinical (P = .003) and radiologic (P = .03) MS activity was significantly lower in natalizumab continuers than in natalizumab switchers or quitters, confirming a protective effect of natalizumab on the risk of relapse in natalizumab continuers compared with natalizumab quitters (OR, 4.40; 95% CI, 1.72-11.23) and natalizumab switchers (OR, 3.28; 95% CI, 0.99-10.79). No disease rebound was observed in natalizumab quitters. After natalizumab discontinuation, 1 patient developed progressive multifocal leukoencephalopathy during the observation period, with complete recovery. CONCLUSIONS AND RELEVANCE: This study provides class III evidence of an increased risk of MS activity resumption after natalizumab discontinuation. Therapy discontinuation after 24 doses in natalizumab-responding patients should be considered only if the risk of progressive multifocal leukoencephalopathy is high and outweighs the benefits of continuing the drug. TRIAL REGISTRATION: Osservatorio Nazionale Sulla Sperimentazione Clinica dei Medicinali No. 131/2010.
Background
Autonomic symptoms and sleep disorders are common non-motor symptoms of Parkinson disease (PD), which are correlated with poor quality of life for patients.
Purpose
To assess the frequency ...of autonomic symptoms in a consecutive series of PD patients and to correlate them with other motor and non-motor symptoms.
Methods
All consecutive non-demented PD patients who underwent an extensive evaluation including Hoehn and Yahr staging, Unified Parkinson’s Disease Rating Scale, Beck’s Depression Inventory, Neuropsychiatric Inventory, PDQ-39 Scale, the Parkinson’s diseases Sleep Scale, the Epworth Sleepiness Scale and SCOPA-AUT scale were enrolled. Comorbidity has been also considered. Supine to standing position blood pressure and cardiac frequency changes were also measured.
Results
135 PD patients were included (mean age at interview 67.7; mean disease duration: 5.3 years). Patients were stratified according to mean SCOPA-AUT scale score (13.1). Those with higher SCOPA-AUT scale score were significantly older, had longer disease duration, worse disease stage, worse quality of sleep, were more severely affected, and were also taking a higher dosage of levodopa. At multivariate analysis, older age, longer disease duration, and worse quality of sleep were independently associated with higher SCOPA-AUT scale scores.
Conclusions
Our results remark the role of autonomic symptoms in PD. In our patient population, characterized by mild to moderate disease severity, most of the patients complained of autonomic nervous system involvement (84 %). A significant association between autonomic symptoms and sleep disorders was also observed.
Low vitamin D levels have been recognised as an important risk factor for autoimmune diseases, including multiple sclerosis (MS). MS is a multifactorial disease, the pathogenesis of which contributes ...both to genetic and environmental factors. Polymorphisms in genes codifying molecules involved in vitamin D homeostasis have been associated with hypovitaminosis D. However, the influence of polymorphisms of Klotho, which codify a protein with a pivotal role in vitamin D metabolism, have never been investigated. The aim of this study was to evaluate the association among genetic variants of Klotho, namely rs1207568 and rs9536314, serum 25(OH)D
levels, and multiple sclerosis (both risk and disease progression).
107 patients with MS and 133 healthy controls were enrolled in this study. Serum 25(OH)D
levels and genotyping of Klotho SNPs were evaluated in all participants by high-performance liquid chromatography and real-time polymerase chain reaction, respectively.
Allelic and genotypic frequencies did not differ between patients and controls. Concerning rs1207568, we found a trend toward lower serum 25(OH)D
levels in MS patients with A allele (mutant), both in heterozygosis (AG) and in homozygosis (AA), in comparison to MS patients with G allele in homozygosis (GG) (AG + AA 20.5 ±6.3 µg/l; GG 22.5 ±7.5 µg/l,
= 0.07).
Our findings did not identify a role of Klotho in the genetic susceptibility to MS.
Introduction
Natalizumab (NTZ) discontinuation can be followed by multiple sclerosis (MS) disease reactivation. Currently no disease-modifying drug (DMD) has been shown to be able to abolish disease ...reactivation. The aims of the current study were: (1) to determine the frequency of MS reactivation after NTZ discontinuation; (2) to evaluate predictors of reactivation risk, and (3) to compare the effect of different treatments in reducing this risk.
Methods
Data from 132 patients with MS followed-up for 2 years before NTZ treatment and 1 year after interruption were collected from two Italian MS centers and retrospectively evaluated.
Results
Overall, 72 of 132 patients (54.5%) had relapses after NTZ discontinuation and 60 of 125 patients (48%), who had magnetic resonance imaging, had radiological reactivation. Rebound was observed in 28 of 132 patients (21.2%). A higher number of relapses in the 2 years before NTZ treatment, a longer washout period, and a lower number NTZ infusions correlated with reactivation and rebound. Untreated patients (
n
= 37) had higher clinical and radiological activity and rebound in comparison to patients receiving DMDs. Moreover, a lower risk of relapses was found in patients treated with second-line therapies (NTZ and fingolimod) than in those treated with first-line therapies (interferon beta, glatiramer acetate, teriflunomide, azathioprine). Interestingly, no disease reactivation in off-label treatment (rituximab, autologous hematopoietic stem cell transplantation) was observed.
Conclusion
NTZ discontinuation is a risk for MS reactivation and rebound. An alternative treatment should be promptly resumed mainly in patients with a previous very active disease course and with a shorter NTZ therapy. Second-line therapies demonstrate superiority in preventing relapses after NTZ discontinuation.
Studies reporting an inverse association between Alzheimer's disease (AD) and cancer are scant. Available data are mostly based on ancillary findings of mortality data or obtained from studies ...evaluating frequency of neoplasms in AD patients independently if they occurred before or after AD. Moreover, some studies estimated frequencies of neoplasms in demented individuals, who were not necessarily AD patients. We estimated frequency of tumors preceding the onset of AD in AD patients and compared it to that of age- and gender-matched AD-free individuals. Occurrence of tumors preceding AD onset was assessed through a semi-structured questionnaire. Tumors were categorized as benign, malignant, or of uncertain classification and as endocrine-related or not. Odds ratios (OR), used as measure of the association between the two diseases, were adjusted for tumor categories and known risk factors for AD and tumors. We included 126 AD patients and 252 matched controls. Tumor frequency before AD onset was 18.2% among cases and 24.2% among controls. There was a suggestive trend of an overall inverse association between the two diseases (adjusted OR 0.6; 95% CI 0.4-1.1; p = 0.11). Risk for neoplasms was significantly reduced only for women (adjusted OR, 0.5; 95% CI 0.3-0.9; p = 0.03) and for endocrine related tumors (adjusted OR, 0.5; 95% CI 0.2-1; p = 0.04). Our study confirms the inverse association reported in previous epidemiological studies. Though our findings might be explained by processes playing an opposite role in tumors development and neurodegeneration, they are also suggestive for a possible role of estrogen.
We describe a patient with frontotemporal dementia (FTD), a tauopathy, who also showed clinical and polysomnographic features of REM sleep behavior disorder (RBD). The patient is a 78-year-old male ...with a 1 year history of behavioral dysfunction involving emotion, character and social functioning. Brain imaging and the results of neuropsychological testing were consistent with a diagnosis of FTD. Sleep symptom onset occurred some years before the behavioral changes, and consisted of unpleasant dreams, vocalization, and prominent motor behaviors. A polysomnography confirmed the diagnosis of RBD. Our findings support the hypothesis that RBD, although more frequent in synucleinopathies, might be a pathological stage in the development of almost every neurodegenerative disorder in which the pathological process involves the cerebral structures that regulate muscle tone during REM sleep.
•PM2.5, PM10 and NO2 are risk factors for Covid-19 pneumonia among MS patients.•We studied the joint exposure to the three pollutants as an environmental mixture.•The most dangerous pollutants within ...the mixture were NO2 and PM2.5.
Many studies investigated the association between air pollution and Covid-19 severity but the only study focusing on patients with Multiple Sclerosis (MS) exclusively evaluated exposure to PM2.5. We aim to study, in a sample of MS patients, the impact of long-term exposure to PM2.5, PM10 and NO2 on Covid-19 severity, described as occurrence of pneumonia.
A 1:2 ratio case-control study was designed, differentiating cases and controls based on Covid-19 pneumonia. Associations between pollutants and outcome were studied using logistic regression. Weighted quantile sum (WQS) logistic regression was used to identify the individual contribution of each pollutant within the mixture; Least Absolute Shrinkage and Selection Operator (LASSO) penalized regression was performed to confirm the variable selection from WQS. All the analyses were adjusted for confounders selected a priori.
Of the 615 eligible patients, 491 patients provided detailed place of exposure and were included in the principal analysis. Higher concentrations of air pollutants were associated with increased odds of developing Covid-19 pneumonia (PM2.5: 3rd vs 1st tercile OR(95% CI)=2.26(1.29;3.96); PM10: 3rd vs 1st tercile OR(95% CI)=2.12(1.22;3.68); NO2: 3rd vs 1st tercile OR(95% CI)=2.12(1.21;3.69)). Pollutants were highly correlated with each other; WQS index was associated to an increased risk of pneumonia (β=0.44; p-value=0.004) and the main contributors to this association were NO2 (41%) and PM2.5 (34%). Consistently, Lasso method selected PM2.5 and NO2.
Higher long-term exposure to PM2.5, PM10 and NO2 increased the odds of Covid-19 pneumonia among MS patients and the most dangerous pollutants were NO2 and PM2.5.
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