Search

Background: The kidney-brain crosstalk has been involved in Alzheimer's disease (AD) with the mechanism remaining unclear. The anti-aging factor Klotho was reported to attenuate both kidney injury and AD pathologies. Objective: To investigate whether plasma Klotho participated in kidney-brain crosstalk in AD. Methods: We enrolled 33 PiB-PET-positive AD patients and 33 amyloid-β (Aβ)-negative age- and sex-matched cognitively normal (CN) controls from the Chongqing Ageing & Dementia Study (CADS). The levels of plasma Klotho, Aβ, and tau in the cerebrospinal fluid (CSF) were measured by enzyme-linked immunosorbent assay. Results: We found higher plasma Klotho and lower estimated glomerular filtration rate (eGFR) levels in AD patients compared with CN. The eGFR was positively associated with Aβ42, Aβ40 levels in CSF and negatively associated with CSF T-tau levels. Plasma Klotho levels were both negatively correlated with CSF Aβ42 and eGFR. Mediation analysis showed that plasma Klotho mediated 24.96% of the association between eGFR and CSF Aβ42. Conclusion: Renal function impacts brain Aβ metabolism via the kidney-brain crosstalk, in which the plasma Klotho may be involved as a mediator. Targeting Klotho to regulate the kidney-brain crosstalk provides potential therapeutic approaches for AD. [ABSTRACT FROM AUTHOR]

Objectives: To evaluate changes in health outcomes between years 2 and 3 after discharge following COVID-19 and to identify risk factors for poor health 3-year post-discharge., Design: This is a multicentre observational cohort study., Setting: This study was conducted in two centres from Wuhan, China., Participants: Eligibility screening has been performed in 3988 discharged laboratory-confirmed adult COVID-19 patients. Exclusion criteria were refusal to participate, inability to contact and death before follow-up. The WHO COVID-19 guidelines on defining disease severity were adopted., Results: 1594 patients participated in the 1-year, 2-year and 3-year follow-ups, including 796 (49.9%) male patients, and 422 (26.5%) patients were classified in the severe disease group. 3 years after discharge, 182 (11.4%) patients still complained of at least one symptom. The most common symptoms were fatigue, myalgia, chest tightness, cough, anxiety, shortness of breath and expectoration. Fatigue or myalgia, the most common symptom cluster, frequently coexisted with chest symptoms and anxiety. Symptom persistence between years 2 and 3 was reported in 70 patients (4.4%) for which intensive care unit (ICU) admission was a risk factor (p=0.038). Of the 1586 patients who completed the chronic obstructive pulmonary disease assessment test (CAT), 97 (6.1%) scored ≥10, with older age being associated with CAT ≥10 (p=0.007)., Conclusions: Between years 2 and 3 after SARS-CoV-2 infection, most patients returned to an asymptomatic state, and only a few were still symptomatic. ICU admission was a risk factor for symptom persistence., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)