The effect of sumac and cinnamon on lipid profile and quality of life in patients with acute myocardial infarction, type 2 diabetes, and overweight/obesity: study protocol for a randomized double-blin

Neuronal and axonal loss represent a major pathological substrate underlying disability in multiple sclerosis (MS)[]. Optical coherence tomography (OCT) is a noninvasive, quick, patient-friendly examination that can provide markers of neuroaxonal loss. Specifically, the macular ganglion cell layer and peripapillary retinal nerve fiber layer (pRNFL)—which contain neurons and axons of the visual pathway, respectively—are associated with gray matter integrity on brain magnetic resonance imaging (MRI) [], as well as physical and cognitive disability in people with MS (pwMS) [, ]. Moreover, OCT measures were associated with progression independent of relapse activity (PIRA) in prior studies [–], suggesting that retinal atrophy reflects relevant neurodegenerative processes in the central nervous system (CNS). However, PIRA is typically based on the expanded disability status scale (EDSS) and thus primarily reflects physical disability []. More recently, the concept of PIRA has been proposed []. Cognitive impairment is a prevalent (34–65%) and disabling manifestation in pwMS, even at early stages of the disease and across all phenotypes. It can develop insidiously and progress gradually or decline abruptly during relapses []. Previous studies showed longitudinal associations between OCT measures and cognitive impairment [–]. Moreover, a threshold of pRNFL thickness ≤ 88 µm has been associated with an increased risk of cognitive decline [, ]. In another study, both macular ganglion cell-inner plexiform layer (mGCIPL) and pRNFL at baseline (BL), as well as their annual thinning rates, predicted physical and cognitive disability progression []. However, these studies did not further differentiate cognitive decline due to PIRA versus relapse-associated worsening. Thus, the value of OCT measures on prognosticating the risk of cognitive PIRA has not been investigated yet. Our primary aim was to assess the value of retinal layer thickness (as quantified by OCT) to prognosticate events of cognitive PIRA in pwMS. Moreover, we aimed at investigating the relationship between OCT measures and risk of cognitive PIRMA events (progression independent of relapses MRI activity) as well as of events with purely cognitive PIRA, not accompanied by worsening in physical disability (EDSS).