Search

The conversion from mild cognitive impairment (MCI) to dementia is influenced by several factors, including comorbid conditions such as metabolic and vascular diseases. Understanding the impact of these comorbidities can help in the disease management of patients with a higher risk of progressing to dementia, improving outcomes. In the current study, we aimed to analyze data from a large cohort of MCI (n = 188) by principal component analysis (PCA) and cluster analysis (CA) to classify patients into distinct groups based on their comorbidity profile and to predict the risk of conversion to dementia. From our analysis, four clusters emerged. CA showed a significantly higher rate of disease progression for Cluster 1, which was predominantly characterized by extremely high obesity and diabetes compared to other clusters. In contrast, Cluster 3, which was defined by a lower prevalence of all comorbidities, had a lower conversion rate. Cluster 2, mainly including subjects with traumatic brain injuries, showed the lowest rate of conversion. Lastly, Cluster 4, including a high load of hearing loss and depression, showed an intermediate risk of conversion. This study underscores the significant impact of specific comorbidity profiles on the progression from MCI to dementia, highlighting the need for targeted interventions and management strategies for individuals with these comorbidity profiles to potentially delay or prevent the onset of dementia.

Alzheimer's disease (AD) causes a significant challenge to global healthcare systems, with limited effective treatments available. This review examines the landscape of novel therapeutic strategies for AD, focusing on the shortcomings of traditional therapies against amyloid-beta (Aβ) and exploring emerging alternatives. Despite decades of research emphasizing the role of Aβ accumulation in AD pathogenesis, clinical trials targeting Aβ have obtained disappointing results, highlighting the complexity of AD pathophysiology and the need for investigating other therapeutic approaches. In this manuscript, we first discuss the challenges associated with anti-Aβ therapies, including limited efficacy and potential adverse effects, underscoring the necessity of exploring alternative mechanisms and targets. Thereafter, we review promising non-Aβ-based strategies, such as tau-targeted therapies, neuroinflammation modulation, and gene and stem cell therapy. These approaches offer new avenues for AD treatment by addressing additional pathological hallmarks and downstream effects beyond Aβ deposition.

Growing evidence suggests that neuroinflammation plays a critical role in the pathogenesis of neurodegenerative diseases. Peripheral markers of inflammation, including blood cell counts and their ratios, such as the neutrophil-to-lymphocyte ratio (NLR), have been reported as an easily accessible and reliable proxy of central nervous system inflammation. However, the role of peripheral inflammation in dementia and Mild Cognitive Impairment (MCI) still needs to be clarified. In the current study, we aimed to assess the prognostic role of the NLR and other peripheral markers of inflammation in a sample of 130 amnestic MCI, followed up for two to five years. The Mini-Mental state examination (MMSE) score at baseline and follow-up visits was used to assess global cognitive status at each visit and the degree of cognitive decline over time. Baseline peripheral markers of inflammation included blood cell counts and ratios, specifically the NLR, the platelet-to-lymphocyte ratio (PLR), the monocyte-to-lymphocyte ratio (MLR), and the systemic immune inflammation index (SII). After classifying subjects into CONVERTERS and non-CONVERTERS (respectively, patients converting to dementia and subjects showing stability at the last available follow-up), we compared peripheral markers of inflammation among groups ed correlated them with cognitive measures, testing the ability of significant factors to predict conversion to dementia. In our cohort, CONVERTERS showed lower baseline MMSE scores ( p -value = 0.004) than non-CONVERTERS. In addition, CONVERTERS had statistically elevated NLR ( p -value = 0.005), PLR ( p -value = 0.002), and SII levels ( p -value = 0.015), besides a lower number of lymphocytes ( p -value = 0.004) compared with non-CONVERTERS. In a logistic regression analysis, baseline MMSE scores and NLR predicted conversion to dementia. Tertiles analysis showed that MCI with the highest NLR values had a higher conversion risk. Our study supports the hypothesis that a dysregulation of peripheral inflammation involving both lymphocytes and neutrophils may play a role in the pathogenesis of dementia, even at the early stages of neurodegeneration, as in the MCI condition.

The COVID-19 pandemic has led to unprecedented demand on the global healthcare system. Remarkably, at the end of 2021, COVID-19 vaccines received approvals for human use in several countries worldwide. Since then, a solid base for response in the fight against the virus has been placed. COVID-19 vaccines have been shown to be safe and effective drugs. Nevertheless, all kinds of vaccines may be associated with the possible appearance of neurological complications, and COVID-19 vaccines are not free from neurological side effects. Neurological complications of COVID-19 vaccination are usually mild, short-duration, and self-limiting. However, severe and unexpected post-vaccination complications are rare but possible events. They include the Guillain-Barré syndrome, facial palsy, other neuropathies, encephalitis, meningitis, myelitis, autoimmune disorders, and cerebrovascular events. The fear of severe or fatal neurological complications fed the "vaccine hesitancy" phenomenon, posing a vital communication challenge between the scientific community and public opinion. This review aims to collect and discuss the frequency, management, and outcome of reported neurological complications of COVID-19 vaccines after eighteen months of the World Health Organization's approval of COVID-19 vaccination, providing an overview of safety and concerns related to the most potent weapon against the SARS-CoV-2.

Background: The novel coronavirus disease of 2019 (COVID-19) outbreak provoked a profound healthcare system reorganization. This study aimed to compare the reasons for requesting a non-deferrable neurological evaluation before the COVID-19 pandemic and during the lockdown., Methods: Retrospective observational study including non-deferrable neurological outpatients before the pandemic (pre-COVID-19 group, n = 223) and during the Italian second wave of the COVID-19 pandemic (LOCKDOWN group, n = 318)., Results: The number of patients sent for cerebrovascular disorders, headache, and vertigo significantly dropped between the pre-COVID-19 era and the lockdown period. While in the pre-COVID-19 group, the most frequent diagnosis was cerebrovascular disorder; neuropsychiatric disorders ranked first in the LOCKDOWN group. Moreover, the percentage of appropriate non-deferrable neurological evaluations significantly increased in the LOCKDOWN group compared with the pre-COVID-19 group., Discussion: Our study shows a significant increase of neuropsychiatric disorders in non-deferrable neurologic evaluations during the Italian second wave of the COVID-19. Overall, cases were more severe and required a more complex management during the lockdown compared with the pre-COVID era. These findings confirm that a careful approach to prevent the psychological consequences of the pandemic is needed, and long-term rearrangements of the healthcare system are desirable to guarantee appropriate management.