Exercise–Linked Irisin: Consequences on Mental and Cardiovascular Health in Type 2 Diabetes

Type 2 diabetes mellitus (T2DM) is a metabolic disorder associated with insulin resistance and hyperglycemia. Chronic exposure to a T2DM microenvironment with hyperglycemia, hyperinsulinemia, oxidative stress and increased levels of proinflammatory mediators, has negative consequences to the cardiovascular system and mental health. Therefore, atherosclerotic cardiovascular diseases (CVD) and mental health issues have been strongly associated with T2DM. Lifestyle modifications, including physical exercise training, are necessary to prevent T2DM development and its associated complications. It is widely known that the regular practice of exercise provides several physiological benefits to subjects with T2DM, such as managing glycemic and blood pressure levels. Different types of exercise, from aerobic to resistance training, are effective to improve mental health and cognitive function in T2DM. Irisin is a myokine produced in response to exercise, which has been pointed as a relevant mechanism of action to explain the benefits of exercise on cardiovascular and mental health in T2DM patients. Here, we review emerging clinical and experimental evidence about exercise-linked irisin consequences to cardiovascular and mental health in T2DM.     

Targeting the Unfolded Protein Response as a Disease-Modifying Pathway in Dementia

Dementia is a global medical and societal challenge; it has devastating personal, social and economic costs, which will increase rapidly as the world’s population ages. Despite this, there are no disease-modifying treatments for dementia; current therapy modestly improves symptoms but does not change the outcome. Therefore, new treatments are urgently needed—particularly any that can slow down the disease’s progression. Many of the neurodegenerative diseases that lead to dementia are characterised by common pathological responses to abnormal protein production and misfolding in brain cells, raising the possibility of the broad application of therapeutics that target these common processes. The unfolded protein response (UPR) is one such mechanism. The UPR is a highly conserved cellular stress response to abnormal protein folding and is widely dysregulated in neurodegenerative diseases. In this review, we describe the basic machinery of the UPR, as well as the evidence for its overactivation and pathogenicity in dementia, and for the marked neuroprotective effects of its therapeutic manipulation in murine models of these disorders. We discuss drugs identified as potential UPR-modifying therapeutic agents—in particular the licensed antidepressant trazodone—and we review epidemiological and trial data from their use in human populations. Finally, we explore future directions for investigating the potential benefit of using trazodone or similar UPR-modulating compounds for disease modification in patients with dementia.     

Neocortical Disconnectivity Disrupts Sensory Integration in Alzheimer's Disease.

The cortical pathology in Alzheimer's disease (AD) should lead to the loss of effective interaction between distinct neocortical areas. This study compared 2 conditions within a single sensory integration task that differed in the demands placed on effective cross-cortical interaction. AD patients were impaired in their ability to bind distinct visual features of a stimulus when this binding placed greater demands on cross-cortical interaction (i.e., motion and color) but were not impaired when this binding placed lesser demands on such interaction (i.e., motion and luminance). In contrast, neurologically intact individuals and patients with Huntington's disease were able to effectively bind features under both conditions. These results provide psychophysical support for the presence of functional disconnectivity in AD and demonstrate the utility of AD for investigating the neurocognitive substrates of sensory integration. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Possible Selves of Individuals With Alzheimer's Disease.

This study is one of the first to examine self-goals and their relationship to affect among individuals with Alzheimer's disease (AD). Using the construct of possible selves, the authors collected data from 50 participants with mild to moderate AD and 50 demographically similar cognitively intact older adults. Findings suggest a resourcefulness and flexibility of the self-system in response to the presence of dementia-related concerns. Positive affect was associated with family-related self-goals of AD participants, indicating particular importance of this domain. Some of these responses may represent goal modifications that result in a more satisfactory adjustment to the illness; further inquiry may lead to a better understanding of resiliency and quality of life in persons with AD. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Alterations of regional cerebral blood flow after NMDA receptor antagonist administration in patients with alcohol‐related dementia

Although N‐methyl‐d ‐aspartate (NMDA) receptor antagonists may have beneficial influences on cognition in patients with alcohol‐related dementia (ARD), their effects on regional cerebral blood flow (rCBF) remain unknown. This study evaluated changes in rCBF in ARD patients after administration of NMDA receptor antagonist for 12 weeks using technetium‐99m ethyl cysteinate dimer (Tc‐99m ECD) single‐photon emission computed tomography (SPECT). Twenty‐eight ARD patients were administered memantine for 12 weeks and underwent clinical evaluations and brain SPECT scans at baseline and follow‐up. Whole‐brain changes in perfusion were examined on a voxel‐by‐voxel basis. At follow‐up, the patients showed reduced rCBF in the left medial frontal gyrus, left cingulate gyrus, left claustrum, right brainstem, left superior temporal gyrus, bilateral fusiform gyrus, and left cerebellum. On the other hand, increased rCBF was found in the bilateral uncus, left parahippocampal gyrus, bilateral superior frontal gyrus, right inferior parietal lobule, left cuneus, and left superior temporal gyrus. Perfusion increases in various brain areas including the superior frontal, parahippocampal, and inferior parietal areas, which may play important roles in the pathophysiology of ARD, suggest potential benefits of NMDA receptor antagonists on brain functions in patients with ARD.     

The Relationship Between Neuropsychological Functioning and Driving Ability in Dementia: A Meta-Analysis.

A meta-analysis of 27 primary studies was conducted to examine the relationship between neuropsychological functioning and driving ability for adults with dementia. When studies using a control group were included, the relationship between cognitive measures and on-road or non-road driving measures was significant for all reported domains; mean correlations ranged from .35 to .65. Caregiver reports of driving ability and cognitive variables were correlated significantly only on measures of mental status and visuospatial skills. When studies using a control group were excluded, moderate mean correlations were observed for visuospatial skills and on-road or non-road measures, and for mental status with non-road tests. Other effects were small or nonsignificant. Implications for basing driving recommendations on neuropsychological testing are discussed. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Immune Signaling Kinases in Amyotrophic Lateral Sclerosis (ALS) and Frontotemporal Dementia (FTD)

Amyotrophic lateral sclerosis (ALS) is the most common neurodegenerative disorder of motor neurons in adults, with a median survival of 3–5 years after appearance of symptoms, and with no curative treatment currently available. Frontotemporal dementia (FTD) is also an adult-onset neurodegenerative disease, displaying not only clinical overlap with ALS, but also significant similarities at genetic and pathologic levels. Apart from the progressive loss of neurons and the accumulation of protein inclusions in certain cells and tissues, both disorders are characterized by chronic inflammation mediated by activated microglia and astrocytes, with an early and critical impact of neurodegeneration along the disease course. Despite the progress made in the last two decades in our knowledge around these disorders, the underlying molecular mechanisms of such non-cell autonomous neuronal loss still need to be clarified. In particular, immune signaling kinases are currently thought to have a key role in determining the neuroprotective or neurodegenerative nature of the central and peripheral immune states in health and disease. This review provides a comprehensive and updated view of the proposed mechanisms, therapeutic potential, and ongoing clinical trials of immune-related kinases that have been linked to ALS and/or FTD, by covering the more established TBK1, RIPK1/3, RACK I, and EPHA4 kinases, as well as other emerging players in ALS and FTD immune signaling.     

Potential Biomarkers for Post-Stroke Cognitive Impairment: A Systematic Review and Meta-Analysis

Stroke is a primary debilitating disease in adults, occurring in 15 million individuals each year and causing high mortality and disability rates. The latest estimate revealed that stroke is currently the second leading cause of death worldwide. Post-stroke cognitive impairment (PSCI), one of the major complications after stroke, is frequently underdiagnosed. However, stroke has been reported to increase the risk of cognitive impairment by at least five to eight times. In recent decades, peripheral blood molecular biomarkers for stroke have emerged as diagnostic, prognostic, and therapeutic targets. In this study, we aimed to evaluate some blood-derived proteins for stroke, especially related to brain damage and cognitive impairments, by conducting a systematic review and meta-analysis and discussing the possibility of these proteins as biomarkers for PSCI. Articles published before 26 July 2021 were searched in PubMed, Embase, the Web of Science, and the Cochrane Library to identify all relevant studies reporting blood biomarkers in patients with stroke. Among 1820 articles, 40 were finally identified for this study. We meta-analyzed eight peripheral biomarker candidates: homocysteine (Hcy), high-density lipoprotein cholesterol (HDL-C), C-reactive protein (CRP), low-density lipoprotein cholesterol (LDL-C), total cholesterol (TC), triglyceride (TG), uric acid, and glycated hemoglobin (HbA1c). The Hcy, CRP, TC, and LDL-C levels were significantly higher in patients with PSCI than in the non-PSCI group; however, the HDL-C, TG, uric acid, and HbA1c levels were not different between the two groups. Based on our findings, we suggest the Hcy, CRP, TC, and LDL-C as possible biomarkers in patients with post-stroke cognitive impairment. Thus, certain blood proteins could be suggested as effective biomarkers for PSCI.     

Selected Natural Products in Neuroprotective Strategies for Alzheimer’s Disease—A Non-Systematic Review

Neurodegenerative disorders such as Alzheimer’s disease (AD) are distinguished by the irreversible degeneration of central nervous system function and structure. AD is characterized by several different neuropathologies—among others, it interferes with neuropsychiatrical controls and cognitive functions. This disease is the number one neurodegenerative disorder; however, its treatment options are few and, unfortunately, ineffective. In the new strategies devised for AD prevention and treatment, the application of plant-based natural products is especially popular due to lesser side effects associated with their taking. Moreover, their neuroprotective activities target different pathological mechanisms. The current review presents the anti-AD properties of several natural plant substances. The paper throws light on products under in vitro and in vivo trials and compiles information on their mechanism of actions. Knowledge of the properties of such plant compounds and their combinations will surely lead to discovering new potent medicines for the treatment of AD with lesser side effects than the currently available pharmacological proceedings.