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The relationship between oral functions and dementia was examined in 7384 older adults (age ≥ 75 years) who visited a dental clinic in Gifu, Japan. Participants without dementia in a baseline survey in April 2018 were followed until March 2021. As oral functions, chewing function, tongue and lip function, and swallowing function were assessed by self-administered questionnaire, by oral diadochokinesis test, and by repetitive saliva swallowing test, respectively. The presence of systemic diseases was based on data obtained from the National Database of Health Insurance of Japan. At follow-up, 415 (6%) participants were diagnosed with dementia. Multivariate logistic regression analyses showed the presence of dementia at follow-up was associated with female (odds ratio [OR] 1.386; 95% confidence interval [CI] 1.117–1.719), age (OR 1.078; CI 1.056–1.101), regular dental checkups (absence; OR 1.452; CI 1.180–1.788), brushing frequency ≥ twice/day (absence; OR 1.510; CI 1.194–1.911), decayed teeth (presence; OR 1.328; CI 1.071–1.648), swallowing function (poor; OR 1.484; CI 1.135–1.939) at baseline. It was found that poor swallowing function was associated with the future onset of dementia. [ABSTRACT FROM AUTHOR]

In the early stages of drug discovery, adequate evaluation of the potential drug–drug interactions (DDIs) of drug candidates is important. Several CYP3A activators are known to lead to underestimation of DDIs. These compounds affect midazolam 1'-hydroxylation but not midazolam 4-hydroxylation. We used both metabolic reactions of midazolam to evaluate the activation and inhibition of CYP3A activators simultaneously. For our CYP inhibition assay using cocktail probe substrates, simultaneous liquid chromatography-tandem mass spectrometry monitoring of 1'-hydroxymidazolam and 4-hydroxymidazolam for CYP3A was established in addition to monitoring of 4-hydroxydiclofenac and 1'-hydroxybufuralol for CYP2C9 and CYP2D6. The results of our cocktail inhibition assay were well correlated with those of a single inhibition assay, as were the estimated inhibition parameters for typical CYP3A inhibitors. In our assay, a proprietary compound that activated midazolam 1'-hydroxylation and tended to inhibit 4-hydroxylation was evaluated along with known CYP3A activators. All compounds were well characterised by comparison of the results of midazolam 1'- and 4-hydroxylation. In conclusion, our CYP cocktail inhibition assay can detect CYP3A activation and assess the direct and time-dependent inhibition potentials for CYP3A, CYP2C9, and CYP2D6. This method is expected to be very efficient in the early stages of drug discovery. [ABSTRACT FROM AUTHOR]