Anti-amyloid monoclonal antibodies have finally achieved their translational breakthrough after many years of unmet expectations. The FDA granted traditional approval to lecanemab in July 2023, and the European Medicines Agency approved it in late 2024 with specific genetic restrictions; meanwhile, donanemab received FDA approval in July 2024 and EMA marketing authorization just one month ago. These agents consistently clear cerebral amyloid and slow clinical decline modestly in early-stage, biomarker-confirmed Alzheimer’s disease (AD). On the other hand, they also create significant safety risks, including amyloid-related imaging abnormalities (ARIA) and substantial operational requirements for health systems that are already under pressure. Therefore, precise risk management based on APOE genotyping and the presence of cerebral amyloid angiopathy and cerebral microbleeds should be performed before therapy is initiated. The near-term agenda should prioritize the following areas of study: (1) biomarker-driven front-end triage (including emerging plasma assays); (2) ARIA-aware care pathways and shared decision making; (3) outcome-based coverage and rational pricing; (4) clinical trials that layer anti-amyloid therapy into combinatorial strategies targeting tau protein, neuroinflammation, and synaptic resilience.

Background: There is currently increasing interest in the implication of traumatic brain injury (TBI) as a potential risk factor for long-term neurodegenerative conditions, such as dementia and Alzheimer’s disease (AD). In this context, we performed a systematic review and meta-analysis to evaluate the association between TBI and the risk of dementia. Methods: A systematic search was performed across multiple electronic databases, including PubMed, Embase, and Cochrane Library, to identify relevant meta-analyses and cohort studies. Studies were included if they reported effect sizes (odds ratios [ORs] or relative risks [RRs]) for the association between TBI, its severity, and the risk of dementia or AD. Meta-analyses were performed using random-effects models to account for heterogeneity, and sensitivity analyses were conducted. Results: A total of six studies were included in the analysis. The pooled results showed that TBI significantly increases the risk of dementia, with an overall odds ratio of 1.81 (95% CI: 1.53–2.14). Mild TBI was associated with a modest increase in dementia risk (OR = 1.96, 95% CI: 1.70–2.26), while moderate-to-severe TBI showed a stronger association (OR = 1.95, 95% CI: 1.55–2.45). In contrast, the association between TBI and AD was less consistent, with the pooled OR for AD being 1.18 (at 95% CI: 1.11–1.25) for mild TBI; however, in several studies, no significant association was observed (OR = 1.02, 95% CI: 0.91–1.15). The results also indicated substantial heterogeneity across studies, particularly in relation to AD outcomes. Conclusions: The findings from this umbrella meta-analysis confirm that TBI is a significant risk factor for dementia, with more severe TBIs conferring a higher risk. While mild TBIs also increase the risk of dementia, the effect is more pronounced in moderate-to-severe injuries. The evidence linking TBI to AD is less robust, with inconsistent findings across studies. Clinicians should consider long-term cognitive screening and management for individuals with a history of TBI, particularly those with moderate-to-severe injuries.

Episodic buffer (EB), a key component of working memory, seems to have a rather complicated function as part of binding processes. Recent papers on the field claim that binding processes of working memory (WM) are assisted by attention and executive functions. On the same page, vascular pathology is gaining more ground as the main underlying cause for many brain pathologies. Hypercholesterolemia, hypertension, obesity, diabetes, lack of exercise and smoking are the most common risk factors that people of all ages suffer from and constitute the main vascular risk factors responsible for a possible decline in executive functions and attention. Thus, this research is an attempt to examine the relation between the binding functions of WM and the existence of vascular risk factors via a computerized test focusing on feature binding. The study comprised adults (n = 229) with and without vascular risk factors. The main tools used were a biomarker questionnaire and a feature binding test (FBT). The results showed that participants who report suffering from one or more vascular risk factors had significantly lower performance on specific subtasks of the FBT in comparison to the participants who were healthy. This allows us to assume that there might be a positive association between feature binding and a vascular risk profile in adults, and such a test could be a useful diagnostic tool for early cognitive impairment due to incipient vascular pathology.

The COVID-19 pandemic exposed the fragility of global health systems, as physicians faced extremely challenging conditions including excessive workloads, infection risk, and high patient mortality. We conducted a cross-sectional survey that aimed to assess the post-pandemic prevalence of anxiety, depression, and post-traumatic stress disorder (PTSD) in a sample of Greek physicians who worked on the frontline during the SARS-CoV-2 (COVID-19) pandemic. An online survey was conducted between 1 March and 31 July 2023, in which 200 Greek physicians were invited via e-mail to voluntarily answer a confidential online questionnaire, and 58 of them responded. The survey included two clinically validated tools: the Patient Health Questionnaire-4 (PHQ-4) and the Impact of Event Scale—Revised (IES-R). Univariate correlations of 26 exposure variables with anxiety, depression, combined anxiety/depression, and PTSD were performed. In total, 58 eligible physicians (46.6% female) participated in this study. The rates of anxiety, depression, combined anxiety/depression, and PTSD were 27.5% (95% CI: 16.7–40.9), 31.0% (19.5–44.5), 22.4% (12.5–35.3), and 24.1% (13.9–37.2), respectively. Notably none of the physicians working in a laboratory developed any mental health symptoms. The following factors were found to be associated with the development of higher mental health symptoms: age ≤ 30, employment in healthcare ≤ 10 years, working in COVID-19 wards, working in intensive care units or COVID-19 wards, a history of mental health symptoms, a history of physical conditions, shortages of materials and equipment for diagnosing or treating patients, development of a disease other than COVID-19, and the development of a new mental health condition during the pandemic (p < 0.05 for all associations). Our findings highlight the need to better prepare physicians with adequate materials, infrastructure, and psychological support such that, in a potential future health crisis, they will not be at such high risk of mental health problems.

Background : Impulse control disorders (ICDs) are a common non-motor complication in Parkinson’s disease (PD) patients with multiple negative consequences for the individual and caregivers. Although ICDs are strongly linked to dopaminergic therapy, particularly dopamine agonists, only a percentage of patients develop these behaviors, suggesting the involvement of additional susceptibility factors, including genetic variability. This review aims to analyze current knowledge on the genetic background of ICDs. Methods: A literature search was conducted in the PubMed and Scopus databases for peer-reviewed research regarding the role of genetics in ICDs, published in the English language from 1996 to 2026. References of the selected articles for possible additional articles were also screened in order to include most of the key recent evidence. Genes that are involved in the dopaminergic system play a central role in ICD susceptibility, although the findings in studies are often inconsistent and not replicated. Moreover, variants in genes related to the glutamatergic (e.g., GRIN2B), serotonergic (e.g., HTR2A and TPH2), and opioid systems (e.g., OPRK1 and OPRM1) have been implicated, supporting a multi-system contribution to ICD pathophysiology. Conclusions: Early recognition of genetic factors that increase susceptibility to ICDs in PD patients is awaited to increase diagnostic accuracy and expedite individualized treatment.

Impulse Control Disorders (ICDs) are increasingly recognized non-motor complications in PD patients with multiple negative consequences for the individual and caregivers. ICDs are frequently observed in PD patients treated with dopaminergic agents, however not all patients develop these behavioral disorders, suggesting that other factors may increase susceptibility for PD-ICDs. This review aims to analyze current knowledge on the genetic background of ICDs. For this narrative review article, we searched PubMed and Scopus databases for peer-reviewed research, review articles, and meta-analyses regarding the role of genetics in ICDs, published in the English language with no time restrictions. References of the selected articles for possible additional articles were also screened in order to include most of the key recent evidence. This review pinpoints the critical role of genes that encode for enzymes, transporters and receptors that participate in the dopaminergic system, in ICD pathogenesis. Glutamate receptor, ionotropic, N-methyl-d-aspartate 2B (GRIN2B), involved in the glutamatergic pathway and hydroxytryptamine receptor 2A (HTR2A) and tryptophan hydroxylase 2 (TPH2) involved in the serotoninergic pathways, are also highlighted as important risk factors, as well as Opioid receptor kappa 1 (OPRK1) and Opioid receptor Mu 1 (OPRM1) that participate in the opioid system. Early recognition of genetic factors that increase susceptibility for ICDs in PD patients is awaited to increase diagnostic accuracy and expedite individualized treatment.