Alzheimer's disease (AD) is a neurodegenerative disorder that is characterized by progressive loss of basal forebrain cholinergic neurons, leading to reduction in transmission through cholinergic fibers involved in processes of attention, learning, and memory. Mitochondria provide and regulate cellular energy and are crucial for proper neuronal activity and survival. Mitochondrial dysfunction is evident in early stages of AD and is involved in AD pathogenesis. This review focuses on the evidence supporting a clear association between amyloid-β toxicity, mitochondrial dysfunction, oxidative stress and neuronal damage/death in Alzheimer's disease. To date, the beta amyloid (Aβ) cascade hypothesis still remains the main pathogenetic model of Alzheimer's disease (AD), but its role in the majority of sporadic AD cases is uncertain. Furthermore, the "mitochondrial cascade hypothesis" could explain many of the biochemical, genetic, and pathological features of sporadic AD. This hypothesis promotes mutations in mitochondrial DNA (mtDNA) as the basis for Alzheimer's disease. The mutations could lead to energy failure, increased oxidative stress, and accumulation of Aβ, which in a vicious cycle reinforces the mtDNA damage and oxidative stress.

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Background: Frontline healthcare workers (HCWs) are at risk of developing post-traumatic stress disorder (PTSD) due to the nature of their work and, due to the additional stress and mental fatigue brought on by the COVID-19 pandemic, this risk has increased significantly. A proper understanding of the risk factors for PTSD in this context is crucial to the development of both preventive and corrective measures that will improve the psychological and emotional health of HCWs and reduce their predisposition to PTSD in the short and long term. This study was conducted to determine the prevalence and associated risk factors of PTSD among frontline HCWs in Riyadh, Saudi Arabia, during the COVID-19 pandemic. Methods: This cross-sectional survey study examined responses from emergency medical services personnel (paramedics, nurses, and physicians) in eleven large public hospitals in Riyadh, Saudi Arabia, between June 01 and July 01, 2020. The total number of respondents was 613. The PTSD Checklist for the Diagnostic and Statistical Manual of Mental Disorders (PCL-5), a self-administered tool, was used to diagnose PTSD. Additionally, demographic factors, such as age, gender, race, marital status, occupation, and years of experience, were identified, and the effects of these factors were assessed using statistical analysis. Results: The results revealed a prevalence of PTSD of 33.4% among participants. The highest prevalence was found among paramedics and nurses, while physicians had the lowest prevalence. The study also found statistically significant differences in PTSD scores based on marital status, job title, and years of experience. Half of the participants were aware of the availability of psychological/emotional support and perceived the process for obtaining that support to be clear and accessible. Conclusion: Frontline healthcare workers are at increased risk of developing PTSD, with the degree of risk significantly associated with marital status, job title, years of experience, and the accessibility of psychological/emotional support. Healthcare organisations within Saudi Arabia and elsewhere should use this information to strengthen their psychological and emotional support systems and reduce the risk of PTSD in their employees.