Human-induced climate change has accelerated in recent decades, causing adverse health effects. However, the impact of the changing climate on neurological disorders in the older population is not well understood. We applied time-varying Cox proportional hazards models to estimate the associations between hospital admissions for dementia and the mean and variability of summer and winter temperatures in New England. We estimated seasonal temperatures for each New England zip code using a satellite-based prediction model. By characterizing spatial differences and temporal fluctuations in seasonal temperatures, we observed a lower risk of dementia-associated hospital admissions in years when local temperatures in either summer (hazard ration [HR] = 0.98; 95% confidence interval [CI]: 0.96, 1.00) or winter (HR = 0.97; 95% CI: 0.94, 0.99) were higher than average, and a greater risk of dementia-associated admissions for older adults living in zip codes with higher temperature variations. Effect modifications by sex, race, age, and dual eligibility were considered to examine vulnerability of population subgroups. Our results suggest that cooler-than-average temperatures and higher temperature variability increase the risk of dementia-associated hospital admissions. Thus, climate change may affect progression of dementia and associated hospitalization costs.

Galectin-3, a β-galactoside-binding lectin, is abnormally increased in cardiovascular disease. Plasma Galectin-3 receives a Class II recommendation for heart failure management and has been extensively studied for multiple cellular functions. The direct effects of Galectin-3 on platelet activation remain unclear. This study explores the direct effects of Galectin-3 on platelet activation and thrombosis. A strong positive correlation between plasma Galectin-3 concentration and platelet aggregation or whole blood thrombus formation was observed in patients with coronary artery disease (CAD). Multiple platelet function studies demonstrated that Galectin-3 directly potentiated platelet activation and in vivo thrombosis. Mechanistic studies using the Dectin-1 inhibitor, laminarin, and Dectin-1^−/− mice revealed that Galectin-3 bound to and activated Dectin-1, a receptor not previously reported in platelets, to phosphorylate spleen tyrosine kinase and thus increased Ca²⁺ influx, protein kinase C activation, and reactive oxygen species production to regulate platelet hyperreactivity. TD139, a Galectin-3 inhibitor in a Phase II clinical trial, concentration dependently suppressed Galectin-3-potentiated platelet activation and inhibited occlusive thrombosis without exacerbating haemorrhage in ApoE^−/− mice, which spontaneously developed increased plasma Galectin-3 levels. TD139 also suppressed microvascular thrombosis to protect the heart from myocardial ischaemia–reperfusion injury in ApoE^−/− mice. Galectin-3 is a novel positive regulator of platelet hyperreactivity and thrombus formation in CAD. As TD139 has potent antithrombotic effects without bleeding risk, Galectin-3 inhibitors may have therapeutic advantages as potential antiplatelet drugs for patients with high plasma Galectin-3 levels. Working model for plasma Galectin-3 directly potentiating platelet activation, and the platelet hyperreactivity suppressing effect of Galectin-3 inhibitor TD139 in coronary artery disease. Accumulated Galectin-3 in plasma directly activates Dectin-1 receptor to potentiate platelet activation (platelet aggregation and ATP release), which enhances in vivo thrombosis and myocardial ischaemia–reperfusion injury. Galectin-3 inhibitor TD139 specifically inhibits Galectin-3-induced platelet hyperreactivity to ameliorate atherothrombosis and myocardial infarction in coronary artery disease.