Impact of Current Alcohol Consumption on Cognitive Function in Patients with Self-Perceived Memory Decline: A Comparative Study of Subjective Cognitive Decline, Mild Cognitive Impairment and Alzheimer-Type Dementia Groups

Background@#Alcohol consumption has been considered as a modifiable risk factor for dementia development and alcohol-related brain damage may further impair cognitive abilities in dementia patients. This study aimed to find out the differences in cognitive function according to current alcohol drinking in patients with self-perceived memory decline, including subjective cognitive decline (SCD), mild cognitive impairment (MCI) and early Alzheimer-type dementia (ATD). @*Methods@#From May 2018 to December 2019, retrospective chart review was performed in patients who visited CHA Bundang Medical Center for cognitive decline. A two-way analysis of variance with interaction test were used to analyze the impact of alcohol consumption on cognitive function between groups. @*Results@#A total of 147 patients was classified into three groups of SCD (n=30), MCI (n=53), and ATD (n=64), and each group was divided into two subgroups of alcohol users and alcohol non-users, according to the current status of alcohol consumption. Between SCD, MCI and ATD groups, scores of clock drawing test and Go/No-go test were significantly lower in current alcohol users of ATD groups compared to the SCD and MCI groups (p<0.05). @*Conclusions@#These results suggest that current alcohol consumption has detrimental effects especially on the frontal/executive function in early ATD patients. Considering the association between frontal/executive function and ADL, our finding suggests that cessation of alcohol intake may be a therapeutic strategy to prevent ADL deterioration in patients with ATD.

The Brain Donation Program in South Korea

PURPOSE: Obtaining brain tissue is critical to definite diagnosis and to furthering understanding of neurodegenerative diseases. The present authors have maintained the National Neuropathology Reference and Diagnostic Laboratories for Dementia in South Korea since 2016. We have built a nationwide brain bank network and are collecting brain tissues from patients with neurodegenerative diseases. We are aiming to facilitate analyses of clinic-pathological and image-pathological correlations of neurodegenerative disease and to broaden understanding thereof. MATERIALS AND METHODS: We recruited participants through two routes: from memory clinics and the community. As a baseline evaluation, clinical interviews, a neurological examination, laboratory tests, neuropsychological tests, and MRI were undertaken. Some patients also underwent amyloid PET. RESULTS: We recruited 105 participants, 70 from clinics and 35 from the community. Among them, 11 died and were autopsied. The clinical diagnoses of the autopsied patients included four with Alzheimer's disease (AD), two with subcortical vascular dementia, two with non-fluent variant primary progressive aphasia, one with leukoencephalopathy, one with frontotemporal dementia (FTD), and one with Creutzfeldt-Jakob disease (CJD). Five patients underwent amyloid PET: two with AD, one with mixed dementia, one with FTD, and one with CJD. CONCLUSION: The clinical and neuropathological information to be obtained from this cohort in the future will provide a deeper understanding of the neuropathological mechanisms of cognitive impairment in Asia, especially Korea.

Potential role of leptin in angiogenesis: leptin induces endothelial cell proliferation and expression of matrix metalloproteinases in vivo and in vitro

Leptin, the product of ob gene, is an endocrine hormone that regulates adipose tissue mass. Recently, leptin has been found to generate a growth signal involving a tyrosine kinase-dependent intracellular pathway and promote angiogenic processes via activation of leptin receptor (Ob-R) in endothelial cells. However, it is not clear how leptin functions to promote multi-step processes involved in the neovascularization at the atherosclerotic plaque. We have examined the expression of matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs) and Ob-R in human atherosclerotic lesions, leptin-mediated angiogenesis in vivo and in vitro. Immunohistochemical analysis of human atherosclerotic aorta revealed an increased expression of Ob-R in the intima of neorevascularized regions and of both MMPs and TIMPs predominantly in the endothelial lining of intimal neovessels and macrophages/foam cells. In the rat corneal angiogenesis assay, leptin elicited a comparable sensitivity of angiogenic activity to those of vascular endothelial growth factor (VEGF). The immunohistological analysis of the leptin-treated rat cornea showed definitive rises in Ob-R, MMPs and TIMPs expression as well as those of VEGF receptor (VEGFR-1). Leptin (10-40 ng/ml) induced proliferation of the human umbilical vein endothelial cells (HUVECs) and elevation of MMP-2, MMP-9, TIMP-1, and TIMP-2 expression in a dose-dependent manner. Leptin also induced increases of MMP-2, MMP-9, TIMP-1, and Up-regulated the human coronary artery smooth muscle cells (HCASMCs). These findings suggest that leptin, a hormone with pluralistic properties including a mitogenic activity on vascular endothelial cells, plays a role in matrix remodeling by regulating the expression of MMPs and TIMPs. Taken together, our findings further provide evidences for leptin's role as an angiogenesis inducer in the normal organ (rat cornea) and in aberrant vasculature under duress like atherosclerosis.

Transforming Growth Factor-beta1(TGF-beta1) Synthesis of Human Peritoneal Mesothelial Cell / 대한신장학회잡지

OBJECTIVE: to investigate the effect of high glucose and spent peritoneal dialysate on the TGF-beta1 synthesis of cultured human peritoneal MC(HPMC); to examine the effect of costimulation with high glucose or dialysate and cytokines, interleukin-1beta(IL-1beta) and tumor necrosis factor-alpha(TNF-alpha), on transforming growth factor(TGF-beta1) synthesis of HPMC. DISIGN: HPMCs were exposed to different concentrations of glucose(30, 60 & 90 mM/L) or spent peritoneal dialysate for 48 hours in the absence or presence of IL-1beta(1ng/ml) and TNF-alpha(1ng/ml). TGF-beta1 mRNA expression was assessed by Northern blot analysis and TGF-beta1 protein synthesis and release by Western blot analysis with immunoprecipitation. RESULTS: Exposure of MC to high glucose condition(30mM, 60mM & 90mM of D- glucose) induced 2.3-, 3.6- and 4.0-fold increases in TGF-beta1 mRNA expression of MC with enhanced TGF-beta1 protein synthesis and secretion into the media. Incubation with spent dialysate also significantly increased TGF-beta1 mRNA expression & protein secretion compared to control media(P<0.05) Stimulation with IL-1beta(1ng/ml) or TNF-alpha(1ng/ml) significantly increased TGF-beta1 mRNA expression after 48 hours above the control level by 2.7-fold and 2.1-fold, respectively. However, TNF-alpha-induced increase in TGF-beta1 mRNA expression was not translated into TGF-beta1 protein secretion whereas IL-1beta stimulation induced a significant increase in TGF-beta1 protein secretion as well as TGF-beta1 mRNA expression. Combined stimulation of high glucose or spent dialysate together with IL-1beta or TNF-alpha showed a greater increase in TGF-beta1 mRNA expression and protein secretion compared to stimulation with high glucose or spent dialysate alone. CONCLUSION: Our results clearly show that high glucose concentration of peritoneal dialysate and spent dialysate themselves might be sufficient to stimulate the production of TGF-beta1 by peritoneal mesothelial cell. This state of chronic induction of TGF-beta1 is further exaggerated in the presence of peritonitis because of stimulatory effect of proinflammatory cytokines, resulting in the augmented TGF-beta1 synthesis, thus promoting peritoneal fibrosis.