Research suggests that social, physical, and cognitively challenging activities during lifetime, could mitigate the negative effects of aging on cognitive function. This effect is explained by the increased cognitive reserve (CR) resulting from such factors; in fact, such activities, by altering structural and functional properties of the human brain, equip one with more effective compensatory mechanisms to resist brain damage before the presentation of severe clinical symptoms. Therefore, applying appropriate modifications in one's lifestyle and activities may be effective in lowering the risk of developing dementia and cognitive dysfunction in old age, especially in brain areas that are susceptible to aging. In this paper, we are going to review relevant studies discussing the association between important modifiable factors, known as CR proxies (i.e., educational attainment, occupational complexity, physical activity, social engagement, bilingualism, leisure activities, and Mediterranean diet), and different domains of cognitive function, which are affected either in the process of healthy aging or neurodegenerative diseases. K E Y W O R D Saging, cognitive reserve, dementia, neural compensation, neural plasticity Edited by Yoland Smith F I G U R E 1 Mechanisms involved in life-time cognitive ability. Brain reserve, the intrinsic brain ability to maintain cognitive function which is dependent on brain structure, and cognitive reserve, which comprises the compensatory changes in brain structure and function and is promoted by several activities How to cite this article: Amanollahi M, Amanollahi S, Anjomshoa A, Dolatshahi M. Mitigating the negative impacts of aging on cognitive function; modifiable factors associated with increasing cognitive reserve.

Schizophrenia is a mental disorder in which functional and structural brain networks are disrupted. Classical network analysis has been used by many researchers to quantify brain networks and to study the network changes in schizophrenia, but unfortunately metrics used in this classical method highly depend on the networks' density and weight; the comparisons made by this method are biased. The minimum spanning tree (MST) is an alternative method to solve this problem, but its usefulness in studying the schizophrenic brain network has not been examined yet. In the present study, we quantified structural brain networks using MST metrics to conduct group analysis between age and sex matched schizophrenic patients and healthy controls. Many MST metrics including Kappa, gamma, max, Betweenness centrality (BC), leaf number, and diameter were found to have significantly changed between two groups that implied a disruption in the whole brain integrity. This was unlike the brain segregation, which was not altered in the schizophrenia group. These results have consistency with Classical network analysis works and demonstrate the MST potential as a powerful method to be used in researches, studying schizophrenic brain connectome.

Introduction: It has been proposed that oxidative stress plays a crucial role in vancomycin-induced nephrotoxicity (VIN). Objectives: The present study aimed to investigate the nephroprotective effects of lycopene, as a powerful antioxidant, on VIN. Patients and Methods: In the present study, individuals who received vancomycin (VCM) for any indication were assigned to drug (n=28) and control (n=30) groups. The individuals in the drug group received 25 mg of oral lycopene daily for 10 days started concurrently with VCM and the patients in the placebo group received placebo tablets with VCM. Serum levels of creatinine (SCr) and blood urea nitrogen (BUN) as well as creatinine clearance (CrCl) were determined and recorded before the start of interventions, every other day during therapy, and 12 hours after the last dose of VCM in 10th day of treatment for all participants. Finally, the mean values of the measured parameters were compared between the groups. Results: The mean values of SCr were significantly lower in drug group compared to placebo at the 4th (0.85 ± 0.18 vs. 0.98 ± 0.22, P=0.016) and 6th (0.83 ± 0.18 vs. 0.95 ± 0.21, P=0.029) days. Also, CrCl was significantly higher in the drug group at the 4th day compared to placebo (105.82 ± 20.09 vs. 94.67 ± 20.53, P=0.041). Regarding VCM-induced AKI, no case was reported in any group. Conclusion: Lycopene has the potential for diminution of VCM-induced nephrotoxicity (VIN). However, more investigations with larger sample size are necessary to confirm this effect.

Purpose Macrophages play an important role in mediating damage after Spinal cord injury (SCI) by secreting macrophage migration inhibitory factor (MMIF) as a secondary injury mediator. We aimed to systematically review the role of MMIF as a therapeutic target after traumatic SCI. Methods Our systematic review has been performed according to the PRISMA 2009 Checklist. A systematic search in the scientific databases was carried out for studies published before 20 February 2019 from major databases. Two researchers independently screened titles. The risk of bias of eligible articles was assessed, and data were extracted. Finally, we systematically analyzed and interpreted related data. Results 785 papers were selected for the title and abstract screening. 12 papers were included for data extraction. Eight animal studies were of high quality and the remaining two were of medium quality. One of the two human studies was of poor quality and the other was of fair quality. MMIF as a pro-inflammatory mediator can cause increased susceptibility to glutamate-related neurotoxicity, increased nitrite production, increased ERK activation, and increased COX2/PGE2 signaling pathway activation and subsequent stimulation of CCL5-related chemotaxis. Two human studies and six animal studies demonstrated that MMIF level increases after SCI. MMIF inhibition might be a potential therapeutic target in SCI by multiple different mechanisms (6/12 studies). Conclusion Most animal studies demonstrate significant neurologic improvement after administration of MMIF inhibitors, but these inhibitors have not been studied in humans yet. Further clinical trials are need to further understand MMIF inhibitor utility in acute or chronic SCI. Level of Evidence I Diagnostic: individual cross-sectional studies with the consistently applied reference standard and blinding.