Background:
The risk factors for conversion from relapsing-remitting to secondary progressive multiple sclerosis remain highly contested.
Objective:
The aim of this study was to determine the ...demographic, clinical and paraclinical features that influence the risk of conversion to secondary progressive multiple sclerosis.
Methods:
Patients with adult-onset relapsing–remitting multiple sclerosis and at least four recorded disability scores were selected from MSBase, a global observational cohort. The risk of conversion to objectively defined secondary progressive multiple sclerosis was evaluated at multiple time points per patient using multivariable marginal Cox regression models. Sensitivity analyses were performed.
Results:
A total of 15,717 patients were included in the primary analysis. Older age (hazard ratio (HR) = 1.02, p < 0.001), longer disease duration (HR = 1.01, p = 0.038), a higher Expanded Disability Status Scale score (HR = 1.30, p < 0.001), more rapid disability trajectory (HR = 2.82, p < 0.001) and greater number of relapses in the previous year (HR = 1.07, p = 0.010) were independently associated with an increased risk of secondary progressive multiple sclerosis. Improving disability (HR = 0.62, p = 0.039) and disease-modifying therapy exposure (HR = 0.71, p = 0.007) were associated with a lower risk. Recent cerebral magnetic resonance imaging activity, evidence of spinal cord lesions and oligoclonal bands in the cerebrospinal fluid were not associated with the risk of conversion.
Conclusion:
Risk of secondary progressive multiple sclerosis increases with age, duration of illness and worsening disability and decreases with improving disability. Therapy may delay the onset of secondary progression.
IMPORTANCE: The role of inflammatory disease activity as a determinant of disability in progressive-onset multiple sclerosis (MS) remains contested. OBJECTIVE: To examine the association of ...superimposed relapses in progressive-onset MS on disease outcomes. DESIGN, SETTING, AND PARTICIPANTS: Observational cohort study from MSBase, a prospectively collected, international database. Data were collected between January 1995 and February 2017. Analyses began in February 2017. From 44 449 patients at time of extraction, 1419 eligible patients (31.9%) were identified for analysis. Inclusion criteria consisted of primary progressive MS (PPMS) or progressive-relapsing MS (PRMS), adult-onset disease, and minimum data set (including ≥3 visits with disability recorded, ≥3 months between second and last visit). Data were analyzed using multivariable regression models (Andersen-Gill) with mixed effects. Two sensitivity analyses to exclude both relapse-related disability progression and bout-onset progressive MS were performed. EXPOSURES: Grouped according to presence or absence of relapse, defined as an acute episode of clinical worsening. Quantifiable disability change or correlation on imaging was not required to confirm relapse. MAIN OUTCOMES AND MEASURES: Cumulative hazard of disability progression. RESULTS: Patients with PRMS were younger than those with PPMS (mean SD age, 46 15 vs 51 10 years, Cohen d = 0.40) and demonstrated a mean lower Expanded Disability Status Scale score (mean SD score, 4.0 3 vs 4.5 2.5, Cohen d = 0.28) at inclusion. The ratio of men to women was similar in the PRMS and PPMS groups (252:301 vs 394:472). The overall mean (SD) age was 48 (11) years for men and 50 (10) years for women. Likelihood of confirmed disability progression was lower in patients with superimposed relapses (hazard ratio HR, 0.83; 95% CI, 0.74-0.94; P = .003). Proportion of follow-up time spent on disease-modifying therapy significantly reduced the hazard of confirmed disability progression in the cohort with relapse (HR, 0.96; 95% CI, 0.94-0.99; P = .01) but not in those without relapse (HR, 1.02; 95% CI, 0.99-1.05; P = .26). When accounting for relapse-related progression, the association of disease-modifying therapy in the cohort with superimposed relapse was no longer observed (HR, 1.10; 95% CI, 0.96-1.24; P = .16). CONCLUSIONS AND RELEVANCE: In progressive-onset MS, superimposed relapses are associated with a lower risk of confirmed disability progression. This is most likely attributed to the association of disease-modifying therapy with the prevention of relapse-related disability accrual in patients with superimposed relapse. These findings suggest that inflammatory relapses are an important and modifiable determinant of disability accrual in progressive-onset disease.
In the 45 years since the first formalized international effort to protect cultural property, 2 significant and conflicting international rationales for protecting and regulating cultural property ...have emerged. One focuses on a global cooperative effort aimed at protecting the cultural heritage of all mankind. The other centers on a highly nationalistic, aggressive attempt by countries rich in historical artifacts to retain and seek the return of cultural items over which they claim rightful ownership. The result of these conflicting approaches thus far is a fractured, inconsistent, and ineffective system for dealing with an undeniably complex and serious dilemma. Attempts to resolve this heated debate must necessarily incorporate and reconcile both sets of competing interests. Traditional international law provided no remedy for recovering illegally exported property. The nature of cultural property and the effects of retentive policies are examined.
Genetic and environmental risk factors contribute to periodontal disease, but the underlying susceptibility pathways are not fully understood. Epigenetic mechanisms are malleable regulators of gene ...function that can change in response to genetic and environmental stimuli, thereby providing a potential mechanism for mediating risk effects in periodontitis. The aim of this study is to identify epigenetic changes across tissues that are associated with periodontal disease.
Self-reported gingival bleeding and history of gum disease, or tooth mobility, were used as indicators of periodontal disease. DNA methylation profiles were generated using the Infinium HumanMethylation450 BeadChip in whole blood, buccal, and adipose tissue samples from predominantly older female twins (mean age 58) from the TwinsUK cohort. Epigenome-wide association scans (EWAS) of gingival bleeding and tooth mobility were conducted in whole blood in 528 and 492 twins, respectively. Subsequently, targeted candidate gene analysis at 28 genomic regions was carried out testing for phenotype-methylation associations in 41 (tooth mobility) and 43 (gingival bleeding) buccal, and 501 (tooth mobility) and 556 (gingival bleeding) adipose DNA samples.
Epigenome-wide analyses in blood identified one CpG-site (cg21245277 in ZNF804A) associated with gingival bleeding (FDR = 0.03, nominal p value = 7.17e-8) and 58 sites associated with tooth mobility (FDR < 0.05) with the top signals in IQCE and XKR6. Epigenetic variation at 28 candidate regions (247 CpG-sites) for chronic periodontitis showed an enrichment for association with periodontal traits, and signals in eight genes (VDR, IL6ST, TMCO6, IL1RN, CD44, IL1B, WHAMM, and CXCL1) were significant in both traits. The methylation-phenotype association signals validated in buccal samples, and a subset (25%) also validated in adipose tissue.
Epigenome-wide analyses in adult female twins identified specific DNA methylation changes linked to self-reported periodontal disease. Future work will explore the environmental basis and functional impact of these results to infer potential for strategic personalized treatments and prevention of chronic periodontitis.
Optimal decision-making balances exploration for new information against exploitation of known rewards, a process mediated by the locus coeruleus and its norepinephrine projections. We predicted that ...an exploitation-bias that emerges in older adulthood would be associated with lower microstructural integrity of the locus coeruleus. Leveraging in vivo histological methods from quantitative MRI-magnetic transfer saturation-we provide evidence that older age is associated with lower locus coeruleus integrity. Critically, we demonstrate that an exploitation bias in older adulthood, assessed with a foraging task, is sensitive and specific to lower locus coeruleus integrity. Because the locus coeruleus is uniquely vulnerable to Alzheimer's disease pathology, our findings suggest that aging, and a presymptomatic trajectory of Alzheimer's related decline, may fundamentally alter decision-making abilities in later life.
Background
The COVID‐19 pandemic has impacted daily life worldwide, with possible negative consequences for cognitive health. Self‐reported cognitive symptoms are linked to the development of ...Alzheimer’s disease and related dementias (ADRDs). Identifying risk and protective factors for cognitive symptoms during the pandemic is an important step towards the development of ADRD prevention efforts. We aimed to examine correlates of cognitive symptoms among middle‐ and older‐age adults in Latin America before the availability of vaccines to prevent COVID‐19, including sociodemographic factors and changes in life.
Method
Spanish‐speaking adults ages 55‐95 (N = 2,382, Table 1) living in Latin America completed an online survey between May and December 2020. Cognitive symptoms were assessed via the 12‐item Everyday Cognition (ECog) questionnaire. Negative (e.g., economic difficulties, limited social activities) and positive (e.g., more quality time with close others, increased time in nature/outside) life changes associated with the pandemic were measured via a subset of items from the Epidemic‐Pandemic Impacts Inventory. Sociodemographic factors included age, years of education, gender, occupation and socioeconomic status (SES). Covariates included time since March 2020 (estimated onset of the pandemic in Latin America), country of survey completion, and having experienced COVID‐19 symptoms. Multivariable linear regression models were ran on ECog total scores including covariates and sociodemographic factors (Model 1), and then adding terms for negative and positive life changes and their interaction (Model 2).
Results
Model 1 showed female gender (p = .04), not currently working (p = .02) and lower SES (p<.001) were independently associated with more cognitive symptoms. Model 2 showed a significant interaction between negative and positive life changes (p<.001), indicating that negative life changes were significantly associated with more cognitive symptoms, but this association was weaker among participants who reported at least one positive life change during the pandemic (Figure 1).
Conclusion
Cognitive symptoms might be more common among certain segments of the Latin American population, including women, and those who are not working and have low SES. The experience of positive life changes during the pandemic might buffer the detrimental impact of negative life changes on cognitive symptoms. These risk and protective factors might be considered in ADRD prevention efforts.
Reviews of Books Moreno, María Paz; Bayo, Juan Carlos; Hughes, Robert D. ...
Bulletin of Spanish studies (2002),
9/13/2020, 2020-09-13, Letnik:
97, Številka:
8
Journal Article
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