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• GV1001 improved memory and cognition in both young and old 3xTg-AD mice. • GV1001 reduced the levels of Aβ oligomers and phosphorylated tau. • GV1001 reduced neuroinflammation by shifting phenotype of microglial and astrocyte. • GV1001 bound to gonadotropin-releasing hormone receptors. • Intracellular cAMP level increased after treatment with GV1001. GV1001 protects neural cells from amyloid-β (Aβ) toxicity and other stressors in in vitro studies and demonstrates clinically beneficial effects in patients with moderate to severe Alzheimer's disease (AD). Here, we investigated the protective effects and mechanism of action of GV1001 in triple transgenic AD (3xTg-AD) mice. We found that GV1001 improved memory and cognition in middle- and old-aged 3xTg-AD mice. Additionally, it reduced Aβ oligomer and phospho-tau (Ser202 and Thr205) levels in the brain, and mitigated neuroinflammation by promoting a neuroprotective microglial and astrocyte phenotype while diminishing the neurotoxic ones. In vitro , GV1001 bound to gonadotropin releasing hormone receptors (GnRHRs) with high affinity. Levels of cyclic adenosine monophosphate, a direct downstream effector of activated GnRHRs, increased after GV1001 treatment. Furthermore, inhibition of GnRHRs blocked GV1001-induced effects. Thus, GV1001 might improve cognitive and memory functions of 3xTg-AD mice by suppressing neuroinflammation and reducing Aβ oligomers levels and phospho-tau by activating GnRHRs and their downstream signaling pathways. [ABSTRACT FROM AUTHOR]

Background: Hyperuricemia in patients with gout is associated with a low risk of neurodegenerative diseases, including dementia. However, the prevalence of dementia in patients with gout has not yet been reported. Objective: To analyze the prevalence of dementia among patients diagnosed with gout by utilizing the Health Insurance and Review Assessment database, a nationwide registry of the South Korean population. Methods: Data from the Health Insurance and Review Assessment database of patients diagnosed with gout between 2011 and 2018 were extracted. The annual prevalence of dementia according to age and sex was analyzed. We investigated whether there was an association between comorbidities and gout medication in patients with both gout and dementia and in patients with only gout. Results: Between 2011 and 2018, the age-adjusted prevalence of dementia per 100,000 persons ranged from 54.0 (95% confidence interval: 47.7–60.2) to 69.9 (95% confidence interval: 65.3–74.5). Compared to previous studies, the prevalence of dementia was lower in patients with gout than in the general population. Patients with both gout and dementia were more likely to be women, have a wide range of comorbidities, and be prescribed gout-related drugs, including allopurinol, febuxostat, nonsteroidal anti-inflammatory drugs, and steroids than patients with gout without dementia. Conclusions: This study demonstrated a relatively low prevalence of dementia in patients with gout. Gout, characterized by hyperuricemia, might be associated with a reduced risk of dementia. [ABSTRACT FROM AUTHOR]

BACKGROUND: A combination of plasma phospho‐tau (p‐tau), amyloid beta (Aβ)‐positron emission tomography (PET), brain magnetic resonance imaging, cognitive function tests, and other biomarkers might predict future cognitive decline. This study aimed to investigate the efficacy of combining these biomarkers in predicting future cognitive stage transitions within 3 years. METHODS: Among the participants in the Korean Brain Aging Study for the Early Diagnosis and Prediction of Alzheimer's Disease (KBASE‐V) study, 49 mild cognitive impairment (MCI) and 113 cognitively unimpaired (CU) participants with Aβ‐PET and brain imaging data were analyzed. RESULTS: Older age, increased plasma p‐tau181, Aβ‐PET positivity, and decreased semantic fluency were independently associated with cognitive stage transitions. Combining age, p‐tau181, the Centiloid scale, semantic fluency, and hippocampal volume produced high predictive value in predicting future cognitive stage transition (area under the curve = 0.879). CONCLUSIONS: Plasma p‐tau181 and Centiloid scale alone or in combination with other biomarkers, might predict future cognitive stage transition in non‐dementia patients. Highlights: ‐Plasma p‐tau181 and Centiloid scale might predict future cognitive stage transition.‐Combining them or adding other biomarkers increased the predictive value.‐Factors that independently associated with cognitive stage transition were demonstrated. [ABSTRACT FROM AUTHOR]

Introduction: This study aimed to determine the efficacy of combining plasma phosphorylated tau (p‐tau)181, amyloid beta (Aβ)42/Aβ40, neurofilament light (NfL), and apolipoprotein E (APOE) genotypes for detecting positive amyloid positron emission tomography (PET), which is little known in the Asian population, in two independent cohorts. Methods: Biomarkers were measured using a single‐molecule array (Simoa) in a cohort study (Asan). All participants underwent amyloid PET. Significant changes in the area under the curve (AUC) and Akaike Information Criterion values were considered to determine the best model. The generalizability of this model was tested using another cohort (KBASE‐V). Results: In the Asan cohort, after adjusting for age and sex, p‐tau181 (AUC = 0.854) or APOE ε4 status (AUC = 0.769) distinguished Aβ status with high accuracy. Combining them or adding NfL and Aβ42/40 improved model fitness. The best‐fit model included the plasma p‐tau181, APOE ε4, NfL and Aβ42/40. The models established from the Asan cohort were tested in the KBASE‐V cohort. Additionally, in the KBASE‐V cohort, these three biomarker models had similar AUC in cognitively unimpaired (AUC = 0.768) and mild cognitive impairment (MCI) (AUC = 0.997) participants. Conclusions: Plasma p‐tau181 showed a high performance in determining Aβ‐PET positivity. Adding plasma NfL and APOE ε4 status improved the model fit without significant improvement in AUC. [ABSTRACT FROM AUTHOR]

Despite recent studies suggesting a declining incidence and prevalence of dementia on a global scale, epidemiologic results with respect to Alzheimer's disease (AD) are lacking due to the methodological limitations inherent to conducting large-scale cohort investigations of this topic. The aim of the current study was to investigate the incidence and prevalence of AD in Korea. We conducted a secondary analysis within the National Health Insurance System (NHIS) database, a unique resource that reports medical information for the entire Korean population. AD diagnoses as well as evaluations of vascular risks were defined based on International Statistical Classification of Diseases (ICD-10) codes along with prescription records. The cut-off age for diagnosing AD was defined as the age of the patient's highest Youden index. In this study, the incidence and prevalence of AD in the Korean population aged 40 years or older showed an overall increase between 2006 and 2015. Although both older and younger age groups showed an increase in the incidence and prevalence of AD, the highest increase was observed in older age groups. Based on the highest Youden's index value (sensitivity + specificity – 1), the cut-off value for the diagnosis of AD was 69 years with an area under the curve (AUC) of 0.92. We found that the incidence of AD was higher in individuals with underlying vascular risks. However, in recent years, the prevalence of AD was conversely found to be lower in individuals with hypertension or dyslipidemia. Despite efforts toward reducing the number of AD cases through educational, policy, and various public health and preventive medicine interventions, the incidence and prevalence of AD continues to grow in Korea. Efforts aimed at early diagnosis and the modification of underlying risks may be critical to reducing the socioeconomic burden of AD. [ABSTRACT FROM AUTHOR]

This study aimed to investigate the risk and prognosis of Alzheimer's disease (AD) and vascular dementia (VaD) in patients with insomnia using the National Health Insurance Service database covering the entire population of the Republic of Korea from 2007 to 2014. In total, 2,796,871 patients aged 40 years or older with insomnia were enrolled, and 5,593,742 controls were matched using a Greedy digit match algorithm. Mortality and the rate of admission to a long-term care facility were estimated using multivariable Cox analysis. Of all patients with insomnia, 138,270 (4.94%) and 26,706 (0.96%) were newly diagnosed with AD and VaD, respectively. The incidence rate ratios for AD and VaD were 1.73 and 2.10, respectively, in patients with insomnia compared with those without. Higher mortality rates and long-term care facility admission rates were also observed in patients with dementia in the insomnia group. Known cardiovascular risk factors showed interactions with the effects of insomnia on the risk of AD and VaD. However, the effects of insomnia on the incidence of AD and VaD were consistent between the groups with and without cardiovascular risk factors. Insomnia is a medically modifiable and policy-accessible risk factor and prognostic marker of AD and VaD. [ABSTRACT FROM AUTHOR]