To Örebro University

Background: Atopic dermatitis is a chronic inflammatory skin disease and inflammation has been implicated in development of other chronic diseases, but few studies have examined the relationship with dementia.

Objectives: This study examines associations of atopic dermatitis (AD) and systemic inflammation in adolescence measured using erythrocyte sedimenta-tion rate (ESR), as well as AD diagnosed in adulthood, with dementia risk.

Methods: We used three Swedish register‐based cohorts. Cohort I (N= 795,680) comprised men, born in 1951–1968, who participated in themilitary conscription examinations with physician‐assessed AD and ESR; Cohort II (N= 1,757,600) included men and women, born in 1951–1968; and Cohort III (N= 3,988,783) included all individuals in Sweden, born in 1930–1968. We used Cox regression, estimating hazard ratios (HR), with thefollow‐up from 50 years of age to dementia diagnosis, date of emigration, death, or 31 December 2018, which ever occurred first. Further, we used asibling comparison design to adjust for unmeasured confounders shared among siblings.

Results: Cohort I: 1466 dementia events were accrued during follow‐up of 7.8 years, with a crude rate of 21.6 [95% confidence interval (CI): 20.6, 22.8] per 100,000 person‐years. Cohort II: 3549 dementia events were accrued duringfollow‐up of 7.4 years, with a crude rate of 23.7 (95% CI: 22.9, 24.5) per 100,000 person‐years. Cohort III: 120,303 dementia events were accrued during follow‐up of 23.7 years, with a crude rate of 180.3 (95% CI: 179.3, 181.3) per 100,000 person‐years. In multivariable analysis using Cohort I, there was no association between AD and dementia [HR 0.68 (95% CI 0.32, 1.43)], norwith moderate [HR 0.71 (95% CI: 0.46, 1.10)] or high [HR 1.23 (95% CI: 0.87, 1.75)] ESR. AD was not associated with dementia risk in Cohort II [HR 1.28(0.97, 1.71)] or Cohort III [HR 1.01 (0.92, 1.11)].

Conclusions: AD was not associated with dementia risk, neither was systemic inflammation measured by ESR in adolescence.

Serious infections may result in greater risk of Parkinson's disease. However, high-quality cohort studies focusing on a potential causal role of different types and sites of infection are lacking. Gastrointestinal infections are of a particular interest due to growing evidence implicating gut dysbiosis in Parkinson's disease aetiology. This population-based cohort study used the Swedish Total Population Register to identify individuals born during 1944-77 and resident in Sweden between 1990 and 2018 (N = 3 698 319). Hospital-treated infections at ages 21-30 and 31-40 years were identified from the National Patient Register. Participants were followed to identify Parkinson's disease diagnoses from age 41 years up to December 31, 2018, when the oldest individual reached 75 years. Cox regression with a sibling comparison design to tackle familial genetic and environmental confounding was used to derive hazard ratios and 95% confidence intervals for each infection site, type, or any infections at ages 21-30 and 31-40 years. During a median follow-up of 15.4 years, 8815 unique Parkinson's disease diagnoses were accrued, with a crude rate of 17.3 (95% confidence interval 17.0, 17.7) per 100 000 person-years. After controlling for shared familial factors, hospital-treated gastrointestinal and respiratory infections between 21 and 30 years of age were associated with a greater risk of Parkinson's disease [hazard ratios 1.35 (95% confidence interval: 1.05, 1.75) and 1.45 (95% confidence interval: 1.08, 1.95), respectively]; no association was found for any infections at age 31-40 [hazard ratio 1.05 (95% confidence interval: 0.93, 1.19)]. After adjustment, no statistically significant associations were observed for other sites including genitourinary and skin. These findings suggest that hospital-treated infections of the gastrointestinal tract and lungs, both of which may have an influence on the gut microbiome, by age 30 years may be risk factors for Parkinson's disease.

Background: Viral infections, particularly Epstein-Barr virus (EBV), have been linked with risk of multiple sclerosis (MS). Given the evidence that SARS- CoV-2 infection can have consequences for the central nervous system (CNS) and autoimmune disorders, it might increase risk of MS and other demyelinating diseases of the CNS.

Objectives: We aimed to assess whether SARS- CoV-2 infection is associated with subsequent diagnoses of non-MS demyelinating CNS diseases, MS, and infectious mononucleosis (IM) due to EBV—an important MS risk factor.

Methods: All residents of Sweden aged 3–100 years were followed between 1st January 2020 and 30th November 2022, excluding those with demyelinating disease prior to 2020, resulting in 9,981,915 individuals. Exposure was classified as SARS- Cov-2 uninfected or infected, the latter divided by severity, and mod-elled as a time-varying covariate (uninfected, infection without hospital admission and infected with hospital admission). Cox regression assessed the risk of three separate outcomes: hospital-diagnosed non-MS demyelinating diseases; MS; and IM due t oEBV, adjusting for sex, year of birth (age), Charlson comorbidity index, healthcare region and country of birth.

Results: Hospital admission for COVID-19 was associated with raised risk of subsequent non-MS demyelinating disease. Rates per 100 000 person years (and 95% confidence intervals [CI]) were 3.8 (3.6– 4.1) among those without a COVID-19 diagnosis and 9.0 (5.1–15.9) among those admitted to hospital for COVID-19, with an adjusted hazard ratio (aHR) and 95% CI of 2.31 (1.30– 4.10). Equivalent associations with MS were rates of 9.5 (9.1–9.9) and 21.0 (14.5–30.5) per 100,000, and an aHR of 2.48 (1.70–3.61). For subsequent IM due to EBV, hospital admission for COVID-19 was associated with a rate of 10.5 (6.2–17.8) per 100,000 compared with 4.7 (4.4–5.0) for those without COVID-19, and an aHR of 5.63 (3.29–9.66).

Conclusions: There was increased risk of CNS demyelinating diseases among people admitted to hospital for COVID-19. COVID-19 was also associated with a raised risk of IM due to EBV, an established risk factor for MS. It is possible that at least a proportion of these associations is due to surveillance or referral bias (due to a previous hospital admission for infection), so future research should continue to follow the population that had COVID-19 for development of MS and other demyelinating diseases, which can have long asymptomatic and prodromal phases.