Dataset Information

Peripheral immune biomarkers and neurodegenerative diseases: A prospective cohort study with 20 years of follow-up.

ABSTRACT:

Objective

To assess the associations of several blood immune biomarkers with the future risks of amyotrophic lateral sclerosis and Parkinson disease in a prospective cohort study with 20 years of follow-up.

Methods

The Swedish Apolipoprotein-Related Mortality Risk study is a longitudinal cohort study including 812,073 participants with repeated blood biomarker measurements between 1985 and 1996 and a follow-up until 2011. Using a Cox model, we first estimated hazard ratios of amyotrophic lateral sclerosis and Parkinson disease in relation to leukocytes, immunoglobulin G, haptoglobin, and uric acid. We further described the temporal changes of these biomarkers during the 20 years prior to the diagnosis of these diseases.

Results

A total of 585 incident cases of amyotrophic lateral sclerosis and 3,769 incident cases of Parkinson disease were identified during the follow-up. Increasing concentrations of leukocytes, haptoglobin, and uric acid were associated with a lower risk of Parkinson disease. No statistically significant association was, however, noted between the studied biomarkers and amyotrophic lateral sclerosis. Parkinson disease patients appeared to have lower levels of leukocytes and haptoglobin between 20 and 10 years before diagnosis and lower levels of uric acid during the 20 years before diagnosis, compared to controls, although statistically significant differences were only noted during parts of the respective time intervals after multivariable adjustment. No clear differences were noted between patients with amyotrophic lateral sclerosis and controls.

Interpretation

If verified in studies of independent populations, our findings may suggest a different role of systemic inflammation on the risk of Parkinson disease compared to amyotrophic lateral sclerosis. ANN NEUROL 2019;86:913-926.

SUBMITTER: Yazdani S

PROVIDER: S-EPMC7611591 | biostudies-literature |

REPOSITORIES: biostudies-literature

ACCESS DATA

Similar Datasets

Project description:BACKGROUND:Hereditary Haemorrhagic Telangiectasia (HHT) is an autosomal dominant genetic disorder with a wide variety of clinical manifestations due to the presence of multiple arteriovenous malformations in various tissues and organs. OBJECTIVE:To study the need for hospital admittance in a group of HHT patients and matched controls during a 20 years follow-up period commencing in 1995. METHODS:All HHT patients in the County of Funen, Denmark, were included. For each patient, three age and sex matched controls were identified at the time of enrolment. Data on all hospitalisations were extracted from the national health registers and compared with clinical records. The hospitalisations were grouped as HHT relevant or not HHT relevant based on the discharge diagnosis (International Classification of Diseases, ICD10) and with particular focus on infections, bleedings and thromboembolic events. Patients with HHT were compared with controls concerning the first time incidence of each discharge diagnosis. RESULTS:We included 73 HHT patients and 219 controls of which one control was lost to follow-up. HHT-patients had significantly more hospitalisations per person caused by infections in joints and bones, but not caused by infections in general. Bleeding episodes were, as expected, more frequent among the HHT-patients. The study revealed a similar incidence of abscesses and thromboembolisms, including in the central nervous system, among the HHT patients and controls. CONCLUSIONS:Based on this study Danish HHT patients had an increased comorbidity of infections in joints and bones and of bleeding episodes. However, the incidence of thromboembolisms, cerebral abscesses and other conditions commonly considered related to HHT was comparable between the patients and the controls. The patients included in this study were closely monitored at a highly specialised HHT Centre where they received relevant diagnostic evaluation, treatment and counselling. Since this is assumed to benefit the overall health of the patients, it may explain why these patients were less prone to comorbidity than other studies have suggested.

Project description:Plasma estrogen and androgen levels are positively associated with postmenopausal breast cancer risk, but how long a single blood measurement can predict risk and whether the associations vary by tumor hormone receptor status remain unclear. We conducted nested case-control analyses within the Nurses' Health Study. Blood samples were collected in 1989-1990 and again in 2000-2002. Among postmenopausal women not using postmenopausal hormones at blood collection, 707 cases were diagnosed through June 2010, with two matched controls per case. We used unconditional logistic regression analyses to estimate the relative risks controlling for other breast cancer risk factors. The intra-class correlation coefficients for two blood measurements collected 10 years apart ranged from 0.54 (dehydroepiandrosterone sulfate, DHEAS) to 0.74 (sex hormone-binding globulin, SHBG). Overall, women in the top (vs. bottom) 25 % of levels of estradiol, free estradiol, testosterone, free testosterone, and DHEAS were at a 50-110 % higher risk of breast cancer (p (trend) < 0.001). SHBG was inversely associated with risk (p (trend) = 0.004). RRs were similar when comparing cases diagnosed 1-10 versus 11-20 years (or 16-20 years) after blood collection (p (interaction) > 0.2). Except for DHEAS, the associations varied significantly by hormone receptor status (p (heterogeneity) ? 0.02). For example, the RRs (95 % CIs) comparing the highest versus lowest quartile were 2.8 (2.0-4.0; p (trend) < 0.001) for ER +/PR + tumors versus 1.1 (0.6-2.1; p (trend) = 0.98) for ER-/PR- tumors for estradiol, and 1.8 (1.3-2.5; p (trend) < 0.001) versus 0.6 (0.3-1.2; p (trend) = 0.35) for testosterone. One measure of circulating sex hormones in postmenopausal women can predict risk of hormone receptor positive breast cancer for up to 16-20 years.