Caffeine occurs naturally in various foods, such as coffee, tea, and cocoa, and it has been used safely as a mild stimulant for a long time. However, excessive caffeine consumption (1~1.5 g/day) can cause caffeine poisoning (caffeinism), which includes symptoms such as anxiety, agitation, insomnia, and gastrointestinal disorders. Recently, there has been increasing interest in the effect of caffeine consumption as a protective factor or risk factor for neurological and psychiatric disorders. Currently, the importance of personalized medicine is being emphasized, and research on sex/gender differences needs to be conducted. Our review focuses on the effect of caffeine consumption on several neurological and psychiatric disorders with respect to sex differences to provide a better understanding of caffeine use as a risk or protective factor for those disorders. The findings may help establish new strategies for developing sex-specific caffeine therapies.

Dementia, characterized by a progressive cognitive decline and a cumulative inability to behave independently, is highly associated with other diseases. Various cardiovascular disorders, such as coronary artery disease and atrial fibrillation, are well-known risk factors for dementia. Currently, increasing evidence suggests that sex factors may play an important role in the pathogenesis of diseases, including cardiovascular disease and dementia. Recent studies show that nearly two-thirds of patients diagnosed with Alzheimer’s disease are women; however, the incidence difference between men and women remains vague. Therefore, studies are needed to investigate sex-specific differences, which can help understand the pathophysiology of dementia and identify potential therapeutic targets for both sexes. In the present review, we summarize sex differences in the prevalence and incidence of dementia by subtypes. This review also describes sex differences in the risk factors of dementia and examines the impact of risk factors on the incidence of dementia in both sexes.

This study aimed to determine the association between statins and the prevention of dementia according to sex differences in elderly patients with ischemic heart disease (IHD). We performed a nationwide retrospective cohort study using the Korean Health Insurance Review and Assessment Service database (2007)(2008)(2009)(2010)(2011)(2012)(2013)(2014)(2015). Among the 264,036 eligible patients aged ≥65 years with IHD, statin users were compared with non-users by propensity score matching at a 1:1 ratio (71,587 in each group). The primary outcome was dementia risk by estimating hazard ratios (HRs) and 95% confidence intervals (CIs). Differential risks of dementia were assessed by sex in the subgroups of statin types, exposure duration, and patient age, implying that sex is an influential factor for the link between statin use and dementia incidence. Among seven commonly prescribed statins, rosuvastatin was associated with the greatest preventive effect on dementia incidence, with an adjusted HR of 0.82 (95% CI = 0.78-0.87). In a subgroup analysis organized by sex, the differential risk of dementia incidence was assessed in each statin group, implying that sex is an influential factor for the link between statin and dementia. This study suggests that appropriate statin use considering sex differences may have beneficial effects on the development of dementia.

Sleep is an essential physiological process, especially for proper brain function through the formation of new pathways and processing information and cognition. Therefore, when sleep is insufficient, this can result in pathophysiologic conditions. Sleep deficiency is a risk factor for various conditions, including dementia, diabetes, and obesity. Recent studies have shown that there are differences in the prevalence of sleep disorders between genders. Insomnia, the most common type of sleep disorder, has been reported to have a higher incidence in females than in males. However, sex/gender differences in other sleep disorder subtypes are not thoroughly understood. Currently, increasing evidence suggests that gender issues should be considered important when prescribing medicine. Therefore, an investigation of the gender-dependent differences in sleep disorders is required. In this review, we first describe sex/gender differences not only in the prevalence of sleep disorders by category but in the efficacy of sleep medications. In addition, we summarize sex/gender differences in the impact of sleep disorders on incident dementia. This may help understand gender-dependent pathogenesis of sleep disorders and develop therapeutic strategies in men and women.

Left ventricular (LV) remodeling, which includes ventricular dilatation and increased interstitial fibrosis after myocardial infarction (MI), is the critical process underlying the progression to heart failure. Therefore, a novel approach for preventing LV remodeling after MI is highly desirable. Yuzu is a citrus plant originating in East Asia, and has a number of cardioprotective properties such as hesperidin. However, no study has proved whether yuzu can prevent LV remodeling. The aim of this study was to determine the effects of yuzu on heart failure (HF) and its potential impact on the LV remodeling process after MI. Our in vivo study using the permanent left anterior descending coronary artery (LAD) occlusion model demonstrate that one week pre-treatment with yuzu or its major metabolite hesperidin before LAD occlusion significantly attenuated cardiac dysfunction, myocyte apoptosis and inflammation. Not only yuzu but also hesperidin inhibited caspase-3 activity, myeloperoxidase expression, α-smooth muscle actin expression, and matrix metalloproteinase-2 activity in a permanent LAD occlusion rat model. To our knowledge, our findings provide the first evidence that yuzu and hesperidin prevent MI-induced ventricular dysfunction and structural remodeling of myocardium.