RESUMO
There has been a progressive increase in the prevalence of obesity and its comorbidities such as type 2 diabetes and cardiovascular diseases worldwide. Recent studies have suggested that the crosstalk between adipose tissue and central nervous system (CNS), through cellular mediators and signaling pathways, may causally link obesity with cognitive decline and give rise to neurodegenerative disorders. Several mechanisms have been proposed in obesity, including inflammation, oxidative stress, insulin resistance, altered lipid and cholesterol homeostasis, which may result in neuroinflammation, altered brain insulin signaling, amyloid-beta (Aß) deposition and neuronal cell death. Since obesity is associated with functional and morphological alterations in the adipose tissues, the resulting peripheral immune response augments the development and progression of cognitive decline and increases susceptibility of neurodegenerative disorders, such as Alzheimer's Disease (AD) and Parkinson's Disease (PD). Studies have also elucidated an important role of high fat diet in the exacerbation of these clinical conditions. However, the underlying factors that propel and sustain this obesity associated cognitive decline and neurodegeneration, remains highly elusive. Moreover, the mechanisms linking these phenomena are not well-understood. The cumulative line of evidence have demonstrated an important role of microRNAs (miRNAs), a class of small non-coding RNAs that regulate gene expression and transcriptional changes, as biomarkers of pathophysiological conditions. Despite the lack of utility in current clinical practices, miRNAs have been shown to be highly specific and sensitive to the clinical condition being studied. Based on these observations, this review aims to assess the role of several miRNAs and aim to elucidate underlying mechanisms that link obesity with cognitive decline and neurodegenerative disorders. Furthermore, this review will also provide evidence for the effect of dietary modulation which can potentially ameliorate cognitive decline and neurodegenerative diseases associated with obesity.
RESUMO
INTRODUCTION: West Virginia has the highest incidence of obesity, smoking, and diabetes within the United States, placing its population at higher risk of stroke. In addition to these endemic risk factors, Appalachia faces various socioeconomic and health care access challenges that could negatively impact stroke incidence and outcomes. At present, there are limited data regarding geographic variables on stroke outcomes in rural Appalachia. We set out to quantify Appalachian geographic patterns of stroke incidence and outcomes. METHODS: This is a retrospective analysis of all patients hospitalized with a diagnosis of stroke in West Virginia's largest tertiary hospital. During the study (2000-2018), 14,488 patients were analyzed, with an emphasis on those who died from stroke (n = 1022). We first used institutional ICD-9/10 data alongside demographics information and chart reviews to evaluate disease patterns while also exploring emerging hot spot pattern changes over time; we then exploited an emerging time series analysis using temporal trends to assess differing instances of stroke occurrence regionally with hot spots defined as higher than expected incidences of stroke and stroke death. RESULTS: Data analysis revealed several hot spots of increasing stroke and mortality rates, many of which achieved statistically significant variance compared to expected norms (P = 0.001). Moreover, this study revealed high-risk zones in rural West Virginia wherein the incidence and mortality rates of stroke are suggestively higher and less resistance to economic change than urban centers. CONCLUSIONS: Stroke incidence and mortality were found to be higher than expected in many areas of rural West Virginia. The higher stroke risk populations correlate with area that may be impacted by socioeconomic factors and limited access to primary care. These high-risk areas may therefore benefit from investments in infrastructure, patient education, and unrestricted primary care.