Sex-Specific Risk Factors and Clinical Dementia Outcomes for White Matter Hyperintensities in a large South Korean Cohort.

Objective: White matter hyperintensities (WMH) on brain MRI images are the most common feature of cerebral small vessel disease (CSVD). Studies have yielded divergent findings on the modifiable risk factors for WMH and WMH's impact on cognitive decline. Mounting evidence suggests sex differences in WMH burden and subsequent effects on cognition. Thus, we aimed to identify sex-specific modifiable risk factors for WMH. We then explored whether there were sex-specific associations of WMH to longitudinal clinical dementia outcomes. Methods: Participants aged 49-89 years were recruited at memory clinics and underwent a T2-weighted fluid-attenuated inversion recovery (FLAIR) 3T MRI scan to measure WMH volume. Participants were then recruited for two additional follow-up visits, 1-2 years apart, where clinical dementia rating sum of boxes (CDR-SB) scores were measured. We first explored which known modifiable risk factors for WMH were significant when tested for a sex-interaction effect. We additionally tested which risk factors were significant when stratified by sex. We then tested to see whether WMH is longitudinally associated with clinical dementia that is sex-specific. Results: The study utilized data from 713 participants (241 males, 472 females) with a mean age of 72.3 years and 72.8 years for males and females, respectively. 57.3% and 59.5% of participants were diagnosed with mild cognitive impairment (MCI) for males and females, respectively. 40.7% and 39.4% were diagnosed with dementia for males and females, respectively. Of the 713 participants, 181 participants had CDR-SB scores available for three longitudinal time points. Compared to males, females showed stronger association of age to WMH volume. Type 2 Diabetes was associated with greater WMH burden in females but not males. Finally, baseline WMH burden was associated with worse clinical dementia outcomes longitudinally in females but not in males. Discussion: Elderly females have an accelerated increase in cerebrovascular burden as they age, and subsequently are more vulnerable to clinical dementia decline due to CSVD. Additionally, females are more susceptible to the cerebrovascular consequences of diabetes. These findings emphasize the importance of considering sex when examining the consequences of CSVD. Future research should explore the underlying mechanisms driving these sex differences and personalized prevention and treatment strategies. Clinical trial registration: The BICWALZS is registered in the Korean National Clinical Trial Registry (Clinical Research Information Service; identifier, KCT0003391). Registration Date 2018/12/14.

Association of Geriatric Depressive Symptoms and Government-Initiated Senior Employment Program: A Population-Based Study.

OBJECTIVE: The impact of the government-initiated senior employment program (GSEP) on geriatric depressive symptoms is underexplored. Unearthing this connection could facilitate the planning of future senior employment programs and geriatric depression interventions. In the present study, we aimed to elucidate the possible association between geriatric depressive symptoms and GSEP in older adults. METHODS: This study employed data from 9,287 participants aged 65 or older, obtained from the 2020 Living Profiles of Older People Survey. We measured depressive symptoms using the Korean version of the 15-item Geriatric Depression Scale. The principal exposure of interest was employment status and GSEP involvement. Data analysis involved multiple linear regression. RESULTS: Employment, independent of income level, showed association with decreased depressive symptoms compared to unemployment (p<0.001). After adjustments for confounding variables, participation in GSEP jobs showed more significant reduction in depressive symptoms than non-GSEP jobs (ß=-0.968, 95% confidence interval [CI]=-1.197 to -0.739, p<0.001 for GSEP jobs, ß=-0.541, 95% CI=-0.681 to -0.401, p<0.001 for non-GSEP jobs). Notably, the lower income tertile in GSEP jobs showed a substantial reduction in depressive symptoms compared to all income tertiles in non-GSEP jobs. CONCLUSION: The lower-income GSEP group experienced lower depressive symptoms and life dissatisfaction compared to non-GSEP groups regardless of income. These findings may provide essential insights for the implementation of government policies and community-based interventions.

Mediating effect of depressive symptoms on the relationship between digital literacy and cognitive function in older adults.

Introduction: Although several studies have examined the individual relationships among digital literacy, cognitive function, and depressive symptoms, few have integrated all three factors into a single model. This study aimed to address this gap by investigating the mediating effect of depressive symptoms on the relationship between digital literacy and cognition. In doing so, we hoped to contribute to a more comprehensive understanding of the complex interplay among these variables and their implications for mental health and well-being. Methods: Participants were 7,988 older adults (65 years or older) who participated in the Living Profiles of Older People Survey 2020. The main type of exposure was digital literacy (communication, information, media, and online transaction literacy). The main outcomes were depressive symptoms measured using the Short Geriatric Depression Scale of Korean version and cognitive function measured using the Mini-Mental State Examination score. Multiple linear regression and mediation analyses were also performed. Results: After adjusting for covariates, our analysis found a significant association between digital literacy and both depressive symptoms and cognitive function (ß of four types of digital literacy and depressive symptoms = -0.123, -0.172, -0.702, and - 0.639, respectively; ß of four types of digital literacy and cognitive function = 2.102, 2.217, 1.711, and 1.436, respectively). Moreover, our study showed that depressive symptoms play a mediating role in the relationship between media and online transaction literacy and cognitive function (95% CI of indirect effects = 0.0647-0.1212 and 0.0639-0.1277, respectively), implying an indirect pathway (digital literacy, depressive symptoms, and cognitive function). Discussion: This study sheds light on the relationship between digital literacy, depressive symptoms, and cognitive function in older adults. We found that depressive symptoms mediated the association between specific aspects of digital literacy (online transaction and media literacy) and cognitive function. Our results indicate that community-based digital literacy programs could be effective in reducing depression and preserving or improving cognitive function in older adults.

Moderators of the Association Between Contact Frequency With Non-Cohabitating Adult Children and Depressive Symptoms Among Community-Dwelling Older Adults.

OBJECTIVE: Contact frequency with adult children plays a critical role in late-life depression. However, evidence on possible moderators of this association remains limited. Moreover, considering alterations in contact modes after the coronavirus disease-2019 pandemic, there is a need to investigate this association post-pandemic to develop effective therapeutic interventions. METHODS: This study included 7,573 older adults who completed the Living Profiles of the Older People Survey in Korea. Participants' contact frequency and depressive symptoms were analyzed. Regression analysis was performed after adjusting for covariates. The moderating effects of variables were verified using a process macro. RESULTS: Multivariable logistic regression analysis revealed that infrequent face-to-face (odd ratio [OR]=1.86, 95% confidence interval [CI]=1.55-2.22) and non-face-to-face contact (OR=1.23, 95% CI=1.04-1.45) in the non-cohabitating adult children group was associated with a higher risk of late-life depression compared to that in the frequent contact group. Linear regression analysis indicated consistent results for face-to-face and non-face-to-face contact (estimate=0.458, standard error [SE]=0.090, p<0.001 and estimate=0.236, SE= 0.074, p=0.001, respectively). Moderation analysis revealed that the association between late-life depression and frequency of face-toface contact was moderated by age, household income quartiles, number of chronic diseases, physical activity frequency, presence of spouse, nutritional status, and whether the effect of frequency of non-face-to-face contact on late-life depression was increased by participation in social activity, frequent physical activity, and good cognitive function (p for interaction<0.05). CONCLUSION: Frequent contact with non-cohabitating children lowers the risk of depression later in life. Several variables were identified as significant moderators of contact frequency and depression symptoms.

The local hypothalamic-pituitary-adrenal axis in cultured human dermal papilla cells.

BACKGROUND: Stress is an important cause of skin disease, including hair loss. The hormonal response to stress is due to the HPA axis, which comprises hormones such as corticotropin releasing factor (CRF), adrenocorticotropic hormone (ACTH), and cortisol. Many reports have shown that CRF, a crucial stress hormone, inhibits hair growth and induces hair loss. However, the underlying mechanisms are still unclear. The aim of this study was to examine the effect of CRF on human dermal papilla cells (DPCs) as well as hair follicles and to investigate whether the HPA axis was established in cultured human DPCs. RESULTS: CRF inhibited hair shaft elongation and induced early catagen transition in human hair follicles. Hair follicle cells, both human DPCs and human ORSCs, expressed CRF and its receptors and responded to CRF. CRF inhibited the proliferation of human DPCs through cell cycle arrest at G2/M phase and induced the accumulation of reactive oxygen species (ROS). Anagen-related cytokine levels were downregulated in CRF-treated human DPCs. Interestingly, increases in proopiomelanocortin (POMC), ACTH, and cortisol were induced by CRF in human DPCs, and antagonists for the CRF receptor blocked the effects of this hormone. CONCLUSION: The results of this study showed that stress can cause hair loss by acting through stress hormones. Additionally, these results suggested that a fully functional HPA axis exists in human DPCs and that CRF directly affects human DPCs as well as human hair follicles under stress conditions.

Polygonum multiflorum extract support hair growth by elongating anagen phase and abrogating the effect of androgen in cultured human dermal papilla cells.

BACKGROUND: Dermal papilla cells (DPCs) play a key role in hair growth among the various cell types in hair follicles. Especially, DPCs determine the fate of hair follicle such as anagen to telogen transition and play a pivotal role in androgenic alopecia (AGA). This study was performed to elucidate the hair growth promoting effects of Polygonum multiflorum extract (PM extract) in cultured human DPCs and its underlying mechanisms. METHODS: The effects of PM extract on cultured DPCs were investigated. Cell viability and mitochondrial activity were measured by CCK-8 and JC-1 analysis, respectively. Western blotting, dot blotting, ELISA analysis, immunocytochemistry and real-time PCR analysis were also performed to elucidate the changes in protein and mRNA levels induced by PM extract. 3D cultured DPC spheroids were constructed for mimicking the in vivo DPs. The hair growth stimulatory effect of PM extract was evaluated using human hair follicle organ culture model. RESULTS: PM extract increased the viability and mitochondrial activity in cultured human DPCs in a dose dependent manner. The expression of Bcl2, an anti-apoptotic protein expressed dominantly in anagen was significantly increased and that of BAD, a pro-apoptotic protein expressed in early catagen was decreased by PM extract in cultured DPCs and/or 3D DPC spheroid culture. PM extract also decreased the expression of catagen inducing protein, Dkk-1. Growth factors including IGFBP2, PDGF and VEGF were increased by PM extract, revealed by dot blot protein analysis. We also have found that PM extract could reverse the androgenic effects of dihydrotestosterone (DHT), the most potent androgen. Finally, PM extract prolonged the anagen of human hair follicles by inhibiting catagen entry in human hair follicle organ culture model. CONCLUSION: Our data strongly suggest that PM extract could promote hair growth by elongating the anagen and/or delaying the catagen induction of hair follicles through activation of DPCs.

CRH receptor antagonists from Pulsatilla chinensis prevent CRH-induced premature catagen transition in human hair follicles.

BACKGROUND: There is a growing interest in the relationship among stress hormones, neuroendocrine signaling, and skin diseases, including hair loss. Previous reports showed that stress hormones inhibit human hair growth and induce early catagen transition. Moreover, a CRH receptor antagonist reversed CRH-induced alopecia in a mouse model, suggesting that antagonization of the CRH receptor is a key clinical strategy to treat stress-induced hair loss. OBJECTIVES: The aim of this study was to investigate the protective effect of CRH receptor antagonists from Pulsatilla chinensis on human hair follicles (hHFs) and human dermal papilla cells (hDPCs). METHODS: hHFs were observed and scored by hair cycle. The levels of cAMP, a second messenger, were measured in each group. In addition, the mRNA and protein levels of factors related to the hair cycle were measured. Furthermore, the expression levels of various members of the mitogen-activated protein kinase (MAPK) signaling pathway related to stress were measured. RESULTS: CRH induced early catagen transition in an ex vivo hair organ culture model. In addition, CRH downregulated the levels of alkaline phosphatase (ALP) and hair anagen-related cytokines in cultured hDPCs. Moreover, CRH induced the phosphorylation of JNK, c-Jun, p38, ERK, and Akt in cultured hDPCs. CRH receptor antagonists isolated from P chinensis reversed these CRH-induced modulations in both ex vivo hair follicles (HFs) and cultured hDPCs. CONCLUSIONS: These results indicate that P chinensis effectively blocks CRH receptor function and that saponin derivatives from P chinensis could be a pharmaceutical and cosmetic approach to treat stress-induced hair loss.

Hair Growth Promoting Effect of Hottuynia cordata Extract in Cultured Human Hair Follicle Dermal Papilla Cells.

Houttuynia cordata (HC) is a traditional oriental herbal medicinal plant widely used as a component of complex prescriptions in Asia for alopecia treatment. The effect of HC on hair growth and its underlying mechanism, however, have not been demonstrated or clarified. In this study, we investigated the hair growth promoting effect of HC in cultured human dermal papilla cells (hDPCs). HC extract was found to stimulate the proliferation of hDPCs and this stimulation might be in part a consequence of activated cellular energy metabolism, because treatment of HC extract increased the generation of nicotinamide adenine dinucleotide (NADH) and ATP through increasing the mitochondrial membrane potential (ΔΨ). In the context of cell cycle, HC extract increased the expression of CDK4 and decreased the expression of CCNA2 and CCNB1, implying that HC extract might induce G1 phase progression of DPCs which resulted in enhanced proliferation. HC extract increased the expression of Bcl2 essential for maintaining hair follicle anagen stage and cell survival. On the contrary, the expression of p16 and p21 was down-regulated by HC extract. In addition, HC extract enhanced the secretion of platelet-derived growth factor (PDGF)-aa and vascular endothelial growth factor (VEGF) and induced phosphorylation of extracellular signal-regulated kinase (ERK) and AKT. Furthermore, HC extract prolonged anagen stage in organ cultured human hair follicles. Our data strongly suggest that HC extract could support hair growth by stimulating proliferation of DPCs and elongating anagen stage, resulted from enhanced cellular energy metabolism and modulation of gene expression related to cell cycle, apoptosis, and growth factors.

Anti-aging Properties of Conditioned Media of Epidermal Progenitor Cells Derived from Mesenchymal Stem Cells.

INTRODUCTION: Reduced number and activities of epidermal stem cells are related to the features of photoaged skin. It was reported that conditioned media from various stem cell cultures are capable of improving the signs of cutaneous aging. This work was performed to establish epidermal progenitor cells derived from mesenchymal stem cells, and to evaluate the anti-aging efficacy of its conditioned media. METHODS: Epidermal progenitor cell culture was established by differentiation from mesenchymal stem cells, and its conditioned medium (EPC-CM) was prepared. Normal human dermal fibroblasts were exposed to hydrogen peroxide and the protective effects of EPC-CM were investigated, monitoring intracellular reactive oxygen species (ROS), cellular defense enzymes, collagen biosynthesis, and mitogen-associated protein kinase (MAPK) signaling. Anti-aging efficacy of cosmetic essence (5% EPC-CM) was evaluated by a clinical test with 25 Korean women aged between 29 and 69. RESULTS: Hydrogen peroxide hindered proliferation of fibroblasts and increased the levels of intracellular ROS. Pretreatment of EPC-CM protected fibroblasts from oxidative stress as shown by accelerated proliferation and reduced ROS generation. EPC-CM effectively prevented hydrogen peroxide-induced alterations of the activities, as well as mRNA and protein levels, of antioxidative enzymes, such as superoxide dismutase, catalase, and glutathione peroxidase. Reduced type I collagen biosynthesis and stimulated phosphorylation of MAPK signaling proteins, induced by oxidative damage, were also prevented by EPC-CM. In clinical study, wrinkle, depression, and skin texture were improved by the topical application of a formulation containing 5% EPC-CM within 4 weeks. CONCLUSION: Epidermal progenitor cell culture was established, and its conditioned medium was developed for anti-aging therapy. EPC-CM improved signs of skin aging in clinical study, possibly via activation of cellular the defense system, as supported by in vitro results.