Ageing: from inflammation to cancer Leonardi, Giulia C; Accardi, Giulia; Monastero, Roberto ...
Immunity & ageing,
01/2018, Letnik:
15, Številka:
1
Journal Article
Recenzirano
Odprti dostop
Ageing is the major risk factor for cancer development. Hallmark of the ageing process is represented by inflammaging, which is a chronic and systemic low-grade inflammatory process. Inflammation is ...also a hallmark of cancer and is widely recognized to influence all cancer stages from cell transformation to metastasis. Therefore, inflammaging may represent the biological phenomena able to couple ageing process with cancer development. Here we review the molecular and cellular pathway involved in age-related chronic inflammation along with its potential triggers and their connection with cancer development.
The term "neuroinflammation" defines the typical inflammatory response of the brain closely related to the onset of many neurodegenerative diseases (NDs). Neuroinflammation is well known, but its ...mechanisms and pathways are not entirely comprehended. Some progresses have been achieved through many efforts and research. Consequently, new cellular and molecular mechanisms, diverse and conventional, are emerging. In listing some of those that will be the subject of our description and discussion, essential are the important roles of peripheral and infiltrated monocytes and clonotypic cells, alterations in the gut-brain axis, dysregulation of the apelinergic system, alterations in the endothelial glycocalyx of the endothelial component of neuronal vascular units, variations in expression of some genes and levels of the encoding molecules by the action of microRNAs (miRNAs), or other epigenetic factors and distinctive transcriptional factors, as well as the role of autophagy, ferroptosis, sex differences, and modifications in the circadian cycle. Such mechanisms can add significantly to understanding the complex etiological puzzle of neuroinflammation and ND. In addition, they could represent biomarkers and targets of ND, which is increasing in the elderly.
Aim of the study was to evaluate possible associations between cognitive dysfunctions and development of Levodopa Induced Dyskinesia (LID). PD patients from the Parkinson's disease Cognitive ...impairment Study cohort who underwent a baseline and follow-up neuropsychological evaluations were enrolled. Mild Cognitive Impairment (PD-MCI) was diagnosed according to MDS level II criteria. The following cognitive domains were evaluated: episodic memory, attention, executive function, visuo-spatial function and language. A domain was considered as impaired when the subject scored 2 standard deviation below normality cut-off values in at least one test for each domain. Levodopa equivalent dose, UPDRS-ME and LID were recorded at baseline and follow-up. To identify possible neuropsychological predictors associated with the probability of LID development at follow-up, Cox proportional-hazards regression model was used. Out of 139 PD patients enrolled (87 men, mean age 65.7 ± 9.4), 18 (12.9%) were dyskinetic at baseline. Out of 121 patients non-dyskinetic at baseline, 22 (18.1%) developed LID at follow-up. The impairment of the attention and executive domains strongly predicted the development of LID (HR 4.45;95%CI 1.49-13.23 and HR 3.46; 95%CI 1.26-9.48 respectively). Impairment of the attention and executive domains increased the risk of dyskinesia reflecting the alteration of common cortical network.
The Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection is characterized by severe flu-like symptoms, which can progress to life-threatening systemic inflammation and multiorgan ...dysfunction. The nervous system is involved in over one-third of patients, and the most common neurological manifestations concern the central nervous system, such as headache, fatigue, and brain fog. The activation of innate, humoral, and cellular immune responses, resulting in a cytokine storm and endothelial and mitochondrial dysfunctions, are the main pathophysiological mechanisms of SARS-CoV-2 infection. Citicoline is an exogenous source of choline and cytidine involved in intracellular phospholipid synthesis, which improves blood flow, brain activity, and mitochondrial dysfunction. This report will present the case of a non-hospitalized, 59-year-old female. After a mild form of SARS-CoV-2 infection, the patient developed cognitive disturbances such as forgetfulness and anomia. The multidimensional neuropsychological assessment revealed an impairment in episodic memory with borderline performance in executive and visuospatial functioning. Cognitive rehabilitation and treatment with citicoline 1000 mg/daily led to a marked improvement in symptoms after six months. Early identification of the neurological sequelae of the Coronavirus Disease 2019 (COVID-19) and timely rehabilitation interventions are required in non-hospitalized long-hauler patients with COVID-19. Long-term treatment with citicoline should be considered as potentially effective in improving cognitive functioning in subjects with Post COVID-19 Neurological Syndrome.
Background
Vascular risk factors (VRFs) may be associated with cognitive decline in early Parkinson’s disease (PD) but results are inconclusive. The identification of modifiable risk factors is ...relevant for prevention and treatment.
Methods
Parkinson’s disease (PD) patients of the PACOS cohort who underwent a baseline and follow-up neuropsychological evaluation were enrolled in the study. PD with Mild Cognitive Impairment (MCI) and dementia (PDD) were diagnosed according to the MDS criteria. A Baseline 1.5 T brain MRI was used to calculate the white matter lesions (WMLs) burden using the Wahlund visual scale. Laboratory data, presence of hypertension, diabetes and use of anti-hypertensive drugs were collected and the Framingham Risk (FR) score was calculated. VRFs predicting PD-MCI and PDD were evaluated using Cox proportional hazard regression model.
Results
Out of 139 enrolled patients, 84 (60.4%) were classified as normal cognition (NC) and 55 (39.6%) as MCI at baseline. At follow-up 28 (33.3%) PD-NC developed MCI and 4 (4.8%) PDD (follow-up time 23.5 ± 10.3 months). Out of 55 PD-MCI patients at baseline, 14 (25.4%) converted to PDD. At multivariate analysis among PD-NC a systolic blood pressure (SBP) > 140 mmHg was the stronger predictor of MCI (adjHR 4.04; 95% CI 1.41–11.3) while the presence of MCI at baseline (adj HR 7.55; 95% CI 1.76–32.3) and a severe WMLs burden (adj HR 2.80; 95% CI 0.86–9.04) were the strongest predictors of PDD, even if this latter association has a trend towards significance.
Conclusion
Hypertension represents the most important modifiable risk factor for PD-MCI in the PACOS cohort, increasing the risk of about four times.
Increasing evidence shows that epigenetics also plays a key role in regulating the pathogenetic mechanism of all types of aortic aneurysms. It is well-known that epigenetic factors modulate gene ...expression. This mechanism appears to be of interest especially knowing the relevance of genetic susceptibility and genetic factors in the complex pathophysiology of aortic aneurysms, and of sporadic forms; in fact, the latter are the result of a close interaction between genetic and modifiable lifestyle factors (i.e., nutrition, smoking, infections, use of drugs, alcohol, sedentary lifestyle, etc.). Epigenetic factors include DNA methylation, post-translational histone modifications, and non-coding RNA. Here, our attention is focused on the role of miRNA in syndromic and sporadic forms of thoracic aortic aneurysms. They could be both biomarkers and targets of novel therapeutic strategies.
Mild cognitive impairment (MCI) is a clinical concept proposed as an intermediate state between normal aging and dementia. This condition has multiple heterogeneous sources, including clinical ...presentation, etiology, and prognosis. Recently, the prevalence and associated features of neuropsychiatric symptoms (NPS) in MCI have been described. We systematically searched the PubMed database (last accessed on August 31, 2008) for articles on NPS in MCI. Included articles used strict selection criteria, and outcome variables were extracted in duplicate; of the 27 articles included, 14 (52%) used prospective cohorts. The global prevalence of NPS in MCI ranged from 35% to 85%. The most common behavioral symptoms were depression, anxiety, and irritability. Hospital-based samples reported a higher global prevalence of NPS than population-based studies; this discrepancy probably reflected differences in demographics, study setting, MCI diagnostic criteria, and behavioral instruments used. Prospective studies showed that NPS, particularly depression, may represent risk factors for MCI or predictors for the conversion of MCI to Alzheimer's disease (AD). NPS are very prevalent in subjects with MCI, displaying a similar pattern of symptoms compared to dementia and AD. Large cohort studies using standardized MCI criteria and behavioral instruments are required to evaluate the prognostic role of NPS in MCI.
The effects of the COVID-19 lockdown on subjects with prodromal phases of dementia are unknown. The aim of this study was to evaluate the motor, cognitive, and behavioral changes during the COVID-19 ...lockdown in Italy in patients with Parkinson's disease (PD) with and without mild cognitive impairment (PD-MCI and PD-NC) and in patients with MCI not associated with PD (MCInoPD).
A total of 34 patients with PD-NC, 31 PD-MCI, and 31 MCInoPD and their caregivers were interviewed 10 weeks after the COVID-19 lockdown in Italy, and changes in cognitive, behavioral, and motor symptoms were examined. Modified standardized scales, including the Neuropsychiatric Inventory (NPI) and the Movement Disorder Society, Unified Parkinson's Disease Rating Scale (MDS-UPDRS) Parts I and II, were administered. Multivariate logistic regression was used to evaluate associated covariates by comparing PD-NC vs. PD-MCI and MCInoPD vs. PD-MCI.
All groups showed a worsening of cognitive (39.6%), pre-existing (37.5%), and new (26%) behavioral symptoms, and motor symptoms (35.4%) during the COVID-19 lockdown, resulting in an increased caregiver burden in 26% of cases. After multivariate analysis, PD-MCI was significantly and positively associated with the IADL lost during quarantine (OR 3.9, CI 1.61-9.58), when compared to PD-NC. In the analysis of MCInoPD vs. PD-MCI, the latter showed a statistically significant worsening of motor symptoms than MCInoPD (OR 7.4, CI 1.09-45.44). Regarding NPI items, nighttime behaviors statistically differed in MCInoPD vs. PD-MCI (16.1% vs. 48.4%,
= 0.007). MDS-UPDRS parts I and II revealed that PD-MCI showed a significantly higher frequency of cognitive impairment (
= 0.034), fatigue (
= 0.036), and speech (
= 0.013) than PD-NC. On the contrary, PD-MCI showed significantly higher frequencies in several MDS-UPDRS items compared to MCInoPD, particularly regarding pain (
= 0.001), turning in bed (p = 0.006), getting out of bed (
= 0.001), and walking and balance (
= 0.003).
The COVID-19 quarantine is associated with the worsening of cognitive, behavioral, and motor symptoms in subjects with PD and MCI, particularly in PD-MCI. There is a need to implement specific strategies to contain the effects of quarantine in patients with PD and cognitive impairment and their caregivers.
SARS-CoV-2 pandemic has caused a collapse of the world health systems. Now, vaccines and more effective therapies have reversed this crisis but the scenario is further aggravated by the appearance of ...a new pathology, occurring as SARS-CoV-2 infection consequence: the long-COVID-19. This term is commonly used to describe signs and symptoms that continue or develop after acute infection of COVID-19 up to several months. In this review, the consequences of the disease on mental health and the neurological implications due to the long-COVID are described. Furthermore, the appropriate nutritional approach and some recommendations to relieve the symptoms of the pathology are presented. Data collected indicated that in the next future the disease will affect an increasing number of individuals and that interdisciplinary action is needed to counteract it.
Cognitive impairment in Parkinson's disease (PD) includes a spectrum varying from Mild Cognitive Impairment (PD-MCI) to PD Dementia (PDD). The main aim of the present study is to evaluate the ...incidence of PD-MCI, its rate of progression to dementia, and to identify demographic and clinical characteristics which predict cognitive impairment in PD patients.
PD patients from a large hospital-based cohort who underwent at least two comprehensive neuropsychological evaluations were retrospectively enrolled in the study. PD-MCI and PDD were diagnosed according to the Movement Disorder Society criteria. Incidence rates of PD-MCI and PDD were estimated. Clinical and demographic factors predicting PD-MCI and dementia were evaluated using Cox proportional hazard model.
Out of 139 enrolled PD patients, 84 were classified with normal cognition (PD-NC), while 55 (39.6%) fulfilled the diagnosis of PD-MCI at baseline. At follow-up (mean follow-up 23.5 ± 10.3 months) 28 (33.3%) of the 84 PD-NC at baseline developed MCI and 4 (4.8%) converted to PDD. The incidence rate of PD-MCI was 184.0/1000 pyar (95% CI 124.7-262.3). At multivariate analysis a negative association between education and MCI development at follow-up was observed (HR 0.37, 95% CI 0.15-0.89;
= 0.03). The incidence rate of dementia was 24.3/1000 pyar (95% CI 7.7-58.5). Out of 55 PD-MCI patients at baseline, 14 (25.4%) converted to PDD, giving an incidence rate of 123.5/1000 pyar (95% CI 70.3-202.2). A five time increased risk of PDD was found in PD patients with MCI at baseline (RR 5.09, 95% CI 1.60-21.4).
Our study supports the relevant role of PD-MCI in predicting PDD and underlines the importance of education in reducing the risk of cognitive impairment.
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