The Role of Natural Antioxidants in the Prevention of Dementia—Where Do We Stand and Future Perspectives

Dementia, and especially Alzheimer’s disease (AD), puts significant burden on global healthcare expenditure through its increasing prevalence. Research has convincingly demonstrated the implication of oxidative stress in the pathogenesis of dementia as well as of the conditions which increase the risk of developing dementia. However, drugs which target single pathways have so far failed in providing significant neuroprotection. Natural antioxidants, due to their effects in multiple pathways through which oxidative stress leads to neurodegeneration and triggers neuroinflammation, could prove valuable weapons in our fight against dementia. Although efficient in vitro and in animal models of AD, natural antioxidants in human trials have many drawbacks related to the limited bioavailability, unknown optimal dose, or proper timing of the treatment. Nonetheless, trials evaluating several of these natural compounds are ongoing, as are attempts to modify these compounds to achieve improved bioavailability

Molecular Pathophysiological Mechanisms in Huntington’s Disease

Huntington’s disease is an inherited neurodegenerative disease described 150 years ago by George Huntington. The genetic defect was identified in 1993 to be an expanded CAG repeat on exon 1 of the huntingtin gene located on chromosome 4. In the following almost 30 years, a considerable amount of research, using mainly animal models or in vitro experiments, has tried to unravel the complex molecular cascades through which the transcription of the mutant protein leads to neuronal loss, especially in the medium spiny neurons of the striatum, and identified excitotoxicity, transcriptional dysregulation, mitochondrial dysfunction, oxidative stress, impaired proteostasis, altered axonal trafficking and reduced availability of trophic factors to be crucial contributors. This review discusses the pathogenic cascades described in the literature through which mutant huntingtin leads to neuronal demise. However, due to the ubiquitous presence of huntingtin, astrocytes are also dysfunctional, and neuroinflammation may additionally contribute to Huntington’s disease pathology. The quest for therapies to delay the onset and reduce the rate of Huntington’s disease progression is ongoing, but is based on findings from basic research

Cognition, Statins, and Cholesterol in Elderly Ischemic Stroke Patients: A Neurologist’s Perspective

Background and Objectives: The efficacy of hydroxy methyl glutaryl-coenzyme A reductase inhibitors (statins) in reducing the incidence of cardiovascular events pushed the target LDL-cholesterol (LDL-C) levels lower and lower in successive guidelines despite signals regarding potential cognitive side effects. We evaluated the relationship between cognitive impairment and LDL-C levels in elderly ischemic stroke patients. Materials and Methods: 29 ischemic stroke patients aged 65 and above with LDL-C levels ≤70 mg/dL, classified according to the TOAST criteria, underwent detailed neuropsychological testing comprising the MMSE test, Montreal Cognitive Assessment (MoCA) and Addenbrooke’s Cognitive Evaluation (ACE-III) test. Their performances were compared to those of 29 age-matched ischemic stroke patients with LDL-Cl levels >71 mg/dL. Results: The MMSE test failed to detect significant cognitive differences between the two groups. The MoCA and ACE-III tests detected impairments in visuo-spatial/executive function, attention, and recall/memory in patients with low LDL-C. A stepwise linear regression model of the ACE-III total scores revealed that LDL-cholesterol levels could contribute to 13.8% of the detected cognitive dysfunction, second in importance only to age, which contributed to 38.8% of the detected impairment. Conclusions: Physicians should be cautious when prescribing statins to elderly people. Hydrophilic ones may be preferred in cognitively impaired patients

Neuroinflammation in Cerebral Ischemia and Ischemia/Reperfusion Injuries: From Pathophysiology to Therapeutic Strategies

Its increasing incidence has led stroke to be the second leading cause of death worldwide. Despite significant advances in recanalization strategies, patients are still at risk for ischemia/reperfusion injuries in this pathophysiology, in which neuroinflammation is significantly involved. Research has shown that in the acute phase, neuroinflammatory cascades lead to apoptosis, disruption of the blood–brain barrier, cerebral edema, and hemorrhagic transformation, while in later stages, these pathways support tissue repair and functional recovery. The present review discusses the various cell types and the mechanisms through which neuroinflammation contributes to parenchymal injury and tissue repair, as well as therapeutic attempts made in vitro, in animal experiments, and in clinical trials which target neuroinflammation, highlighting future therapeutic perspectives

Molecular Mechanisms of Neuroinflammation in Aging and Alzheimer’s Disease Progression

Aging is the most prominent risk factor for late-onset Alzheimer’s disease. Aging associates with a chronic inflammatory state both in the periphery and in the central nervous system, the evidence thereof and the mechanisms leading to chronic neuroinflammation being discussed. Nonetheless, neuroinflammation is significantly enhanced by the accumulation of amyloid beta and accelerates the progression of Alzheimer’s disease through various pathways discussed in the present review. Decades of clinical trials targeting the 2 abnormal proteins in Alzheimer’s disease, amyloid beta and tau, led to many failures. As such, targeting neuroinflammation via different strategies could prove a valuable therapeutic strategy, although much research is still needed to identify the appropriate time window. Active research focusing on identifying early biomarkers could help translating these novel strategies from bench to bedside

The Contribution of Diet Therapy and Probiotics in the Treatment of Sarcopenia Induced by Prolonged Immobilization Caused by the COVID-19 Pandemic

The prolonged immobilization associated with COVID-19 infection and the restrictions imposed by the pandemic have determined major changes in physical activity and eating habits, with a negative impact on physical performance. This study monitored non-pharmacological interventions (diet therapy and probiotics) in managing sarcopenia for patients with recent SARS-CoV-2 history (14 days). A prospective study was performed on 200 patients (between December 2020–December 2021), with SPPB score 2 for Group K—non-DP vs. 6.7 ± 0.57 Kg/m2 for Group K—DP, p = 0.135). After two months, significant difference between initial and final SMI values was determined for Group K—DP (6.92 ± 0.50 kg/m2 vs. 6.77 ± 0.56 kg/m2, p = 0.048). In Group K—DP, at end of study, were more patients with normal SMI (n = 32 → N = 70) values (p p p = 0.122). The hemoglobin level improved significantly following a hyper protein diet enriched with pro-biotics (p = 0.003). Diet therapy, consisting of increased protein intake and specific probiotics and specific physical therapy, demonstrated superiority in improving the functional status of patients with recent COVID-19 infection