Parkinson's disease and diabetes mellitus: common mechanisms and treatment repurposing.

In the last decade, attention has become greater to the relationship between neurodegeneration and abnormal insulin signaling in the central nervous system, as insulin in the brain is implicated in neuronal survival, plasticity, oxidative stress and neuroinflammation. Diabetes mellitus and Parkinson's disease are both aging-associated diseases that are turning into epidemics worldwide. Diabetes mellitus and insulin resistance not only increase the possibility of developing Parkinson's disease but can also determine the prognosis and progression of Parkinsonian symptoms. Today, there are no available curative or disease modifying treatments for Parkinson's disease, but the role of insulin and antidiabetic medications in neurodegeneration opens a door to treatment repurposing to fight against Parkinson's disease, both in diabetic and nondiabetic Parkinsonian patients. Furthermore, it is essential to comprehend how a frequent and treatable disease such as diabetes can influence the progression of neurodegeneration in a challenging disease such as Parkinson's disease. Here, we review the present evidence on the connection between Parkinson's disease and diabetes and the consequential implications of the existing antidiabetic molecules in the severity and development of Parkinsonism, with a particular focus on glucagon-like peptide-1 receptor agonists.

Oral Anticoagulation and Risk of Symptomatic Hemorrhagic Transformation in Stroke Patients Treated With Mechanical Thrombectomy: Data From the Nordictus Registry.

Introduction: We aimed to evaluate if prior oral anticoagulation (OAC) and its type determines a greater risk of symptomatic hemorrhagic transformation in patients with acute ischemic stroke (AIS) subjected to mechanical thrombectomy. Materials and Methods: Consecutive patients with AIS included in the prospective reperfusion registry NORDICTUS, a network of tertiary stroke centers in Northern Spain, from January 2017 to December 2019 were included. Prior use of oral anticoagulants, baseline variables, and international normalized ratio (INR) on admission were recorded. Symptomatic intracranial hemorrhage (sICH) was the primary outcome measure. Secondary outcome was the relation between INR and sICH, and we evaluated mortality and functional outcome at 3 months by modified Rankin scale. We compared patients with and without previous OAC and also considered the type of oral anticoagulants. Results: About 1.455 AIS patients were included, of whom 274 (19%) were on OAC, 193 (70%) on vitamin K antagonists (VKA), and 81 (30%) on direct oral anticoagulants (DOACs). Anticoagulated patients were older and had more comorbidities. Eighty-one (5.6%) developed sICH, which was more frequent in the VKA group, but not in DOAC group. OAC with VKA emerged as a predictor of sICH in a multivariate regression model (OR, 1.89 [95% CI, 1.01-3.51], p = 0.04) and was not related to INR level on admission. Prior VKA use was not associated with worse outcome in the multivariate regression model nor with mortality at 3 months. Conclusions: OAC with VKA, but not with DOACs, was an independent predictor of sICH after mechanical thrombectomy. This excess risk was associated neither with INR value by the time thrombectomy was performed, nor with a worse functional outcome or mortality at 3 months.