坪井 良樹

OBJECTIVES: Mitochondrial dysfunction has been implicated in neurodegenerative diseases, but evidence regarding its association with cognitive performance in the general population remains limited. This study aimed to examine the association between peripheral blood mitochondrial DNA copy number (mtDNA-CN) and cognitive function in the general Japanese population. METHODS: We conducted a cross-sectional analysis of 282 participants (134 men and 148 women) from the Yakumo Study, a population-based health examination in Hokkaido, Japan. Peripheral blood mtDNA-CN was measured by quantitative real-time PCR and categorized into tertiles. Cognitive function was assessed using the short version of the Mini-Mental State Examination (SMMSE), the Logical Memory Test (LMT), and the Digit Cancellation Test (D-CAT). Logistic regression analyses were performed to evaluate the association between mtDNA-CN levels and cognitive performance, with adjustments for relevant demographic and clinical factors. RESULTS: Lower mtDNA-CN was significantly associated with poorer SMMSE scores in women and with reduced D-CAT3 performance-reflecting attention and executive function-in men. No significant associations were observed for LMT scores in either sex. These domain- and sex-specific associations remained consistent after adjustment for potential confounders. CONCLUSIONS: Lower mtDNA-CN was associated with poorer cognitive performance in the general Japanese population, in a cognitive domain- and sex-specific manner. mtDNA-CN thus has potential as a non-invasive biomarker for the early identification of individuals at increased risk of cognitive decline. Longitudinal studies are necessary to evaluate its predictive utility and potential application in dementia prevention strategies.

Although previous studies reported that BP PRS is associated with CVD, it is less explored whether BP PRS and BP are jointly associated with CVD, especially among non-European populations. Therefore, we examined joint associations of BP control and BP polygenic risk score (PRS) with CVD mortality in a Japanese population. Data were obtained from the Japan Multi-Institutional Collaborative Cohort (J-MICC) Study, the multi-centered cohort study with 14 study areas throughout Japan. Of which, we analyzed ~35,000 Japanese individuals (Mean age: 55 years old, Men: 44%) with measured BP data (11,242 and 23,904 participants in subgroup #1 and #2). We developed PRS for systolic blood pressure (SBP) and diastolic blood pressure (DBP) in each subgroup. Participants were followed up from the baseline survey (2005-2014) to the end of 2020. Not elevated BP was defined as SBP ≤ 140 mmHg or DBP ≤ 90 mmHg regardless of antihypertensive medications. During the follow-up period, a total of 381 CVD deaths were observed. Compared with not elevated BP, HRs (95% CI) of CVD mortality were 1.98 (1.37-2.88) for elevated SBP and 2.41 (1.66-3.49) for elevated DBP. Compared to not elevated BP in the lowest PRS tertile, HRs (95% CI) of CVD mortality in the highest PRS tertile were 2.28 (1.17-4.43) for SBP and 3.08 (1.61-5.91) for DBP even though BP was not elevated. These associations in the subgroup #1 were replicated in the subgroup #2. Our findings highlighted the importance of BP PRS to detect a hidden CVD risk strata in addition to laboratory BP measurements.