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Yi-Chia Wei,1– 4 Li-Yuan Huang,1,2,5 Chemin Lin,1,2,6 Yu-Chiau Shyu,1,7 Chih-Ken Chen1,2,6 1Community Medicine Research Center, Chang Gung Memorial Hospital, Keelung, Taiwan; 2College of Medicine, Chang Gung University, Taoyuan, Taiwan; 3Department of Neurology, Chang Gung Memorial Hospital, Keelung, Taiwan; 4Institute of Neuroscience, National Yang-Ming University, Taipei, Taiwan; 5Department of Nursing, Chang Gung Memorial Hospital, Keelung, Taiwan; 6Department of Psychiatry, Chang Gung Memorial Hospital, Keelung, Taiwan; 7Department of Nursing, Chang Gung University of Science and Technology, Taoyuan, TaiwanCorrespondence: Chih-Ken ChenDepartment of Psychiatry, Chang Gung Memorial Hospital at Keelung, No. 200 Lane 208, Jijin 1st Road, Anle District, Keelung City, 204, TaiwanTel +886-2-24329292-2725Fax +886-2-24315931Email kenchen@cgmh.org.twBackground: Major depressive disorder (MDD) presents with emotional and somatic symptoms and sometimes subjective cognitive complaints (SCCs). This study developed a collaborative method to integrate SCC assessment for evaluating late-life MDD.Methods: Residents aged > 50 years in the Community Medicine Research Center of Keelung Chang Gung Memorial Hospital in Taiwan during 2017– 2018 were prospectively recruited in this study. The participants were asked to report their depressive tendency and SCCs using the Taiwanese Depression Questionnaire (TDQ) and the AD8, respectively, and were administered psychiatric evaluation through the Mini–International Neuropsychiatric Interview (MINI). The participants were divided into elderly (age≥ 65 years) and older adult (age 50– 65) groups. The MDD predictive powers were assessed using logistic regression and receiver operating characteristic (ROC) curve analyses.Results: Of the 118 enrolled participants (mean age: 64.81± 4.99, female-to-male ratio: 1.62), 9, 21, and 88 were categorized as those with current MDD, past MDD, and non-MDD on the basis of the MINI results, respectively. After adjustments for age, sex, and sleep quality, the TDQ score (odds ratio: 1.152, p=0.003) and AD8 score (odds ratio: 1.710, p=0.020) were used individually to predict current MDD. Overall, the TDQ individually predicted current MDD well with area under the ROC curve (AUC) of 0.835 (p=0.001). However, in the elderly group (N=63), the TDQ score did not identify current MDD well (AUC: 0.780, p=0.063). After co-considering SCCs, the linear combination of the sum of the TDQ score and four folds of the AD8 score could effectively distinguished elderly people with current MDD from those without it (AUC: 0.875, p=0.013)—with the cutoff of the aforementioned combined score being ≥ 32.Conclusion: The self-reported response to the TDQ is a feasible approach of identifying MDD in community-dwelling people. Combining TDQ and AD8 scores further improved depression detection in elderly people.Keywords: geriatric depression, major depressive disorder, Taiwanese Depression Questionnaires, subjective cognitive complaint, AD8

Background: Subjective cognitive decline (SCD) is one of the early warning signs of objective cognition impairment and dementia. Methods: This cross-sectional study screened SCD and studied multiple domains of mental health, lifestyle, and life quality of the community-dwelling people in the northern coastal region of Taiwan. Results: Among 426 valid AD8 questionnaires, a cutoff of score 2 divided subjects into 115 with SCD (SCD+) and 311 without SCD (SCD–). Analysis of age, sex, body compositions, and blood tests revealed an older age (60.7 ± 10.9 years) of the SCD+ group than the SCD– group (57.6 ± 12.0 years, p < 0.05). Further exclusion of subjects younger than 50 years eliminated age differences and left 100 with SCD (SCD+_50) and 229 without (SCD–_50). Multidomain comparisons of the SCD+_50 group over the SCD–_50 group were made: the Taiwanese Depression Questionnaire found a higher likelihood of depression; the Pittsburgh Sleep Quality Index revealed suboptimal sleep quality; the SF-36 showed inferior function of all 8 aspects of quality of life; the Health-Promoting Lifestyle Profile documented a less health-seeking lifestyle of nutrition, self-actualization, and stress management. Conclusions: Aging increased the SCD risk. People with SCD had suboptimal performance in mental health and life quality in addition to subjective cognition problems.

Periodontitis is a highly prevalent infectious disease associated genetically with coronary heart disease (CHD). The effects of proprotein convertase subtilisin/kexin type 9 (PCSK9), a critical regulator of CHD, on periodontitis have not been studied to date. Here, we found that PCSK9 expression was increased in periodontitis patients and Porphyromonas gingivalis (Pg)-infected mice. Loss of PCSK9 attenuated Pg-induced periodontal bone loss in mice. First, PCSK9 deficiency reduced the release of inflammation-associated cytokines, such as tumor necrosis factor alpha (TNF-α) and interleukin 1β, in vitro and in vivo. Second, its deficiency enhanced Pg and endotoxin clearance during Pg invasion in part by upregulating CD36 and low-density lipoprotein receptor (LDLR), respectively. However, after berberine treatment, periodontal bone regeneration in the PCSK9 knockout group was significantly lower than that in wild-type. This was because PCSK9 overexpression promoted osteogenic differentiation of periodontal ligament stem cells (PDLCs) prechallenged by TNF-α. Furthermore, PCSK9 could rescue PDLC osteogenesis by repressing the NF-κB signaling pathway by interacting with TRAF2. These results suggest that PCSK9 may be a potent drug target for treating periodontitis.

A new naphthol derivative, [F-18]FEONM, has been designed to be a new Tau protein PET imaging molecule for detecting Tau tangle status of Alzheimer's disease in a transgenic mouse model. In order to synthesize this molecule, 2-acetyl-6-methoxynaphthalene was the starting compound and needed five steps preparation to bonding functional and leaving group for preparing the precursor. Radiofluorination on the precursor was carried out by a modified [F-18]FDG autosynthesizer. After half an hour processing, it yielded more than 99% chemical and radiochemical purity product at up to 60% yield. Radiofluorination kinetic study showing 80% [F-18]FEONM would be produced within the first 5 min. The radiofluorination gap function factor is 0.122 for 150 min reaction. Recovery yield of crude [F-18]FEONM could be up to 60% by semi-preparative HILIC HPLC column purification with 95% ethanol elution. Brain glioma tumor mice PET imaging were performed after tail vein injecting [F-18]FEONM. Binding in mice brain tumor reached steady state after 30 min injection and shows 30–70% higher uptake compared to normal mouse. The static brain tumor uptake showed the summation accumulation binding rate was 60% faster than normal mouse. In vitro postmortem AD patient brain slice binding showed 70% higher uptake than normal brain. The uptake of spherical stem cells also showed higher association with neuronal differentiation and PET imaging of Tau and ABeta transgenic mice also showed visualized difference. The specific binding ratio of hippocampus to cerebellum of control mouse is 46.56%, cortex to cerebellum is 11.08% in a 12-month-old P301S Tau transgenic mouse; hippocampus to cerebellum is 106.66%, cortex to cerebellum is 82.48%. Relative ratio of hippocampus to cerebellum of a P301S mouse to control mouse is 2.29, cortex to cerebellum is 7.44.