Potential causal effect of physical activity on reducing the risk of dementia: a 6-year cohort study from the Japan Gerontological Evaluation Study

BACKGROUND: The causal effect of physical activity on reducing dementia risk has been questioned due to the possibility of reverse causation. This study examined the potential causal effects of physical activity on reducing dementia risk using residency in a snowy area as an instrumental variable (IV) representing the physical activity of older adults. METHODS: We used cohort data from the Japan Gerontological Evaluation Study, a longitudinal cohort enrolling people aged 65 or older who were physically and cognitively independent in 2013; study participants were followed for an average of 5.7 years. Participants in the present study included 73, 260 individuals living in 19 municipalities in Japan. Physical activity was measured by self-report questionnaires and the incidence of dementia was ascertained by linking participants to the public registries of long-term care insurance. IV estimation was obtained from a piecewise Cox proportional hazard model using a two-stage regression procedure. RESULTS: During the study period, we ascertained 8714 cases (11.9%) of dementia onset. In the IV analysis, we found that the frequency of physical activity per week was negatively associated with dementia risk, though the association weakened over time (Year 1: hazard ratio = 0.53, 95% confidence interval: 0.39-0.74; Year 4: 0.69, 0.53-0.90; Year 6: 0.85, 0.66-1.10). CONCLUSIONS: Our IV analysis indicated a potential causal effect of physical activity on reducing dementia risk that persisted for at least 4 years of follow-up. Thus, we conclude that physical activity should be recommended for older adults to reduce dementia risk

PD-1 and LAG-3 inhibitory co-receptors act synergistically to prevent autoimmunity in mice

A new mouse model of spontaneous autoimmune disease reveals an important role for the inhibitory co-receptor LAG-3 in suppressing autoimmunity

Role of Activation-Induced Cytidine Deaminase in the Development of Oral Squamous Cell Carcinoma

金沢大学医薬保健研究域医学系Purpose:In humans, activation-induced cytidine deaminase (AID) expression results due to inflammation and this deaminase activity is also involved in carcinogenesis. The aim of this study is to investigate the correlation between AID expression and the clinical classification of oral cancer tissues.Experimental Design:The current study investigated the correlation between AID expression and the clinical classification of oral cancer tissues from 27 patients who underwent surgical resection using immunohistochemistry. Specific AID expression and its induction by cytokine stimulation were investigated in cultured HSC oral cancer cell lines by reverse transcriptase PCR.Results:AID expression was detected in 10 of 27 specimens (37.0%). AID expression was more frequently detected in early-stage cancer, especially in early stage T, than in late-stage cancer (T1/T2 vs. T3/4; P = 0.0493, N0 vs. N1/2/3; P = 0.0793). HSC-2, a nonmetastatic oral cancer cell line, abundantly expressed endogenous AID, whereas no such expression was observed in HSC-3, a metastatic oral cancer cell line. Moreover, AID expression was substantially induced in HSC-2 cells by stimulation of an inflammation-related cytokine, TNF-α.Conclusions:Aberrant AID expression in the oral epithelium would contribute to the initiation of oral squamous cell carcinoma. Avoiding persistent AID inducible condition such as frequent cleaning of oral cavity would play an important role for the prevention of developing oral cancer. © 2013 Nakanishi et al