Alzheimer’s disease is the most common type of dementia, reaching 60–80% of case totals, and is one of the major global causes of the elderly population’s decline in functionality concerning daily life activities. Epidemiological research has already indicated that, in addition to several others metabolic factors, diabetes mellitus type 2 is a risk factor of Alzheimer’s disease. Many molecular pathways have been described, and at the same time, there are clues that suggest the connection between type 2 diabetes mellitus and Alzheimer’s disease, through specific genes, autophagy, and even inflammatory pathways. A systematic review with meta-analysis was conducted, and its main goal was to reveal the multilevel connection between these diseases.

Background: Chronic subdural hematoma (cSDH) is a common neurosurgical condition, particularly among elderly patients. Middle meningeal artery (MMA) embolization has emerged as a minimally invasive adjunctive treatment aimed at reducing recurrence. However, its comparative efficacy and safety remain under investigation. Methods: In this systematic review and meta-analysis, randomized-controlled clinical trial (RCT) data evaluating MMA embolization combined with best medical therapy (BMT) versus BMT alone in adult patients with symptomatic cSDH were pooled. The primary efficacy outcome was recurrence or progression of hematoma at follow-up. Secondary efficacy outcomes included good functional outcome [modified Rankin Scale (mRS) score ≤ 2], independent ambulation (mRS score ≤ 3), and hematoma thickness at follow-up. The primary safety outcome was all-cause mortality. Procedure-related complications were assessed as a secondary safety outcome. Results: Six RCTs were included, comprising 760 patients treated with MMA embolization and 788 patients treated with BMT alone. MMA embolization significantly reduced recurrence compared to BMT alone (RR: 0.50; 95% CI: 0.37–0.69; six studies; I² = 0%; number-needed-to-treat = 13). No significant differences were observed in good functional outcome (RR: 1.01; 95% CI: 0.97–1.05; three studies; I² = 0%), independent ambulation (RR: 1.01; 95% CI: 0.99–1.04; three studies; I² = 0%), or hematoma thickness at follow-up (SMD: −0.1; 95% CI: −0.3 to 0; four studies; I² = 42%). All-cause mortality was similar between the two groups (RR: 1.01; 95% CI: 0.42–2.40; five studies; I² = 44%). The pooled rate of procedure-related adverse events in the MMA embolization-group was 1% (95% CI: 0–3%; two studies; I² = 35%). Conclusions: MMA embolization significantly reduced cSDH recurrence when used as an adjunct to BMT. However, it did not demonstrate a significant impact on functional outcomes or mortality in this meta-analysis. Further research is needed to identify patient subgroups that benefit most from MMA embolization and to evaluate its impact on cognitive function and quality of life using longer follow-up periods.

Endovascular treatment (EVT) is the standard of care for acute ischemic stroke (AIS) due to large vessel occlusions, but its efficacy and safety in medium or distal vessel occlusions (MDVOs) remain uncertain. This systematic review and meta-analysis evaluated EVT plus best medical treatment (BMT) vs BMT alone in patients with MDVO-AIS. MEDLINE, Scopus, and ClinicalTrials.gov were searched through February 2025 for randomized-controlled clinical trial (RCT) data and observational evidence comparing EVT plus BMT vs BMT alone in adults with MDVO-AIS. The primary efficacy outcome was 3-month excellent functional outcome (modified Rankin Scale [mRS]-score 0-1), while good functional outcome (mRS score 0-2), reduced disability (mRS shift analysis), and pooled rates of successful recanalization were assessed as secondary outcomes. The primary safety outcome was symptomatic intracranial hemorrhage (sICH), while any ICH, 3-month all-cause mortality, and procedure-related complications were also evaluated. Thirty-eight studies (3 RCTs, 1 post hoc RCT analysis, 1 RCT individual patient data meta-analysis, and 33 observational studies) were included comprising 4,584 EVT-treated patients (mean age 71 years; 46% females) and 5,468 BMT-only patients (mean age 72; 46% females). Patients receiving EVT had similar rates of 3-month excellent functional outcome compared with BMT alone (risk ratio [RR] 1.02; 95% CI 0.93-1.12; p = 0.676; 30 studies; I² = 67%). The 2 groups did not differ in good functional outcome (RR 1.00; 95% CI 0.94-1.07; p = 0.933; 36 studies; I² = 71%) or reduced disability (common odds ratio 0.92; 95% CI 0.80-1.07; p = 0.290; 10 studies; I² = 20%). The pooled rate of successful recanalization in the EVT arm was 78% (95% CI 75%-82%; 25 studies; I² = 82%). EVT was associated with higher rates of sICH (RR 1.54; 95% CI 1.18-2.01; p = 0.002; 29 studies; I² = 24%), any ICH (RR 1.62; 95% CI 1.38-1.92; p < 0.001; 17 studies; I² = 40%), and 3-month all-cause mortality (RR 1.26; 95% CI 1.05-1.50; p = 0.012; 29 studies; I² = 27%). The pooled rate of procedure-related complications was 8% (95% CI 5%-12%; 8 studies; I² = 76%). No significant subgroup differences emerged when stratified for study design or NIH Stroke Scale strata. In this comprehensive synthesis of available evidence, EVT did not improve functional outcomes compared with BMT in MDVO-AIS, while it increased the risk of hemorrhagic complications and mortality. These findings argue against the routine use of EVT for MDVO-AIS. A key limitation is the predominance of observational data, underscoring the need for further RCTs to refine patient selection. The prespecified protocol of the present systematic review and meta-analysis has been registered in the International Prospective Register of Ongoing Systematic Reviews PROSPERO (registration ID: CRD42025651283).

Stroke is ranked as the second leading cause of death worldwide and a major cause of long-term disability. A potential therapeutic target that could offer favorable outcomes in stroke is the mammalian target of rapamycin (mTOR) pathway. mTOR is a serine/threonine kinase that composes two protein complexes, mTOR complex 1 (mTORC1) and mTOR complex 2 (mTORC2), and is regulated by other proteins such as the tuberous sclerosis complex. Through a significant number of signaling pathways, the mTOR pathway can modulate the processes of post-ischemic inflammation and autophagy, both of which play an integral part in the pathophysiological cascade of stroke. Promoting or inhibiting such processes under ischemic conditions can lead to apoptosis or instead sustained viability of neurons. The purpose of this review is to examine the pathophysiological role of mTOR in acute ischemic stroke, while highlighting promising neuroprotective agents such as hamartin for therapeutic modulation of this pathway. The therapeutic potential of mTOR is also discussed, with emphasis on implicated molecules and pathway steps that warrant further elucidation in order for their neuroprotective properties to be efficiently tested in future clinical trials.

Background and purpose: Sporadic cerebral amyloid angiopathy (CAA) is a small vessel disease, resulting from progressive amyloid-β deposition in the media/adventitia of cortical and leptomeningeal arterioles. We sought to assess the prevalence of baseline characteristics, clinical and radiological findings, as well as outcomes among patients with CAA, in the largest study to date conducted in Greece. Methods: Sixty-eight patients fulfilling the Boston Criteria v1.5 for probable/possible CAA were enrolled and followed for at least twelve months. Magnetic Resonance Imaging was used to assess specific neuroimaging markers. Data regarding cerebrospinal fluid biomarker profile and Apolipoprotein-E genotype were collected. Multiple logistic regression analyses were performed to identify predictors of clinical phenotypes. Cox-proportional hazard regression models were used to calculate associations with the risk of recurrent intracerebral hemorrhage (ICH). Results: Focal neurological deficits (75%), cognitive decline (57%), and transient focal neurological episodes (TFNEs; 21%) were the most common clinical manifestations. Hemorrhagic lesions, including lobar cerebral microbleeds (CMBs; 93%), cortical superficial siderosis (cSS; 48%), and lobar ICH (43%) were the most prevalent neuroimaging findings. cSS was independently associated with the likelihood of TFNEs at presentation (OR: 4.504, 95%CI:1.258–19.088), while multiple (>10) lobar CMBs were independently associated with cognitive decline at presentation (OR:5.418, 95%CI:1.316–28.497). cSS emerged as the only risk factor of recurrent ICH (HR:4.238, 95%CI:1.509–11.900) during a median follow-up of 20 months. Conclusions: cSS was independently associated with TFNEs at presentation and ICH recurrence at follow-up, while a higher burden of lobar CMBs with cognitive decline at baseline. These findings highlight the prognostic value of neuroimaging markers, which may influence clinical decision-making.

Background/Objectives: Cognitive impairment represents a core and prodromal clinical feature of cerebral amyloid angiopathy (CAA). We sought to assess specific cognitive domains which are mainly affected among patients with CAA and to investigate probable associations with neuroimaging markers and Cerebrospinal Fluid (CSF) biomarkers. Methods: Thirty-five patients fulfilling the Boston Criteria v1.5 or v2.0 for the diagnosis of probable/possible CAA were enrolled in this prospective cohort study. Brain Magnetic Resonance Imaging and CSF biomarker data were collected. Every eligible participant underwent a comprehensive neurocognitive assessment. Spearman’s rank correlation tests were used to identify possible relationships between the Addenbrooke’s Cognitive Examination—Revised (ACE-R) sub-scores and other neurocognitive test scores and the CSF biomarker and neuroimaging parameters among CAA patients. Moreover, linear regression analyses were used to investigate the effects of CSF biomarkers on the ACE-R total score and Mini-Mental State Examination (MMSE) score, based on the outcomes of univariate analyses. Results: Cognitive impairment was detected in 80% of patients, and 60% had a coexistent Alzheimer’s disease (AD) pathology based on CSF biomarker profiles. Notable correlations were identified between increased levels of total tau (t-tau) and phosphorylated tau (p-tau) and diminished performance in terms of overall cognitive function, especially memory. In contrast, neuroimaging indicators, including lobar cerebral microbleeds and superficial siderosis, had no significant associations with cognitive scores. Among the CAA patients, those without AD had superior neurocognitive test performance, with significant differences observed in their ACE-R total scores and memory sub-scores. Conclusions: The significance of tauopathy in cognitive impairment associated with CAA may be greater than previously imagined, underscoring the necessity for additional exploration of the non-hemorrhagic facets of the disease and new neuroimaging markers.