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Poor Oral Health Linked with Higher Risk of Alzheimer's Disease.

ABSTRACT: Alzheimer's disease (AD) is a multifactorial neurodegenerative disease characterized by cognitive and behavioral changes in older adults. Emerging evidence suggests poor oral health is associated with AD, but there is a lack of large-scale clinical studies demonstrating this link. Herein, we used the TriNetX database to generate clinical cohorts and assess the risk of AD and survival among >30 million de-identified subjects with normal oral health (n = 31,418,814) and poor oral health (n = 1,232,751). There was a greater than two-fold increase in AD risk in the poor oral health cohort compared to the normal oral health group (risk ratio (RR): 2.363, (95% confidence interval: 2.326, 2.401)). To reduce potential bias, we performed retrospective propensity score matching for age, gender, and multiple laboratory measures. After matching, the cohorts had no significant differences in survival probability. Furthermore, when comparing multiple oral conditions, diseases related to tooth loss were the most significant risk factor for AD (RR: 3.186, (95% CI: 3.007, 3.376)). Our results suggest that oral health may be important in AD risk, regardless of age, gender, or laboratory measures. However, more large-scale cohort studies are necessary to validate these findings and further evaluate links between oral health and AD.

SUBMITTER: Kulkarni MS

PROVIDER: S-EPMC10669972 | biostudies-literature | 2023 Nov

REPOSITORIES: biostudies-literature

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Poor Oral Health Linked with Higher Risk of Alzheimer's Disease.

Kulkarni Mihir S MS Miller Brandi C BC Mahani Manan M Mhaskar Rahul R Tsalatsanis Athanasios A Jain Shalini S Yadav Hariom H

Brain sciences 20231107 11

Alzheimer's disease (AD) is a multifactorial neurodegenerative disease characterized by cognitive and behavioral changes in older adults. Emerging evidence suggests poor oral health is associated with AD, but there is a lack of large-scale clinical studies demonstrating this link. Herein, we used the TriNetX database to generate clinical cohorts and assess the risk of AD and survival among >30 million de-identified subjects with normal oral health (<i>n</i> = 31,418,814) and poor oral health (<i ...[more]

PMID: 38002515

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Project description:Women seem to have a higher vulnerability to Alzheimer's disease (AD), but the underlying mechanisms of this sex dichotomy are not well understood. Here, we first determined the influence of sex on various aspects of Alzheimer's pathology in transgenic CRND8 mice. We demonstrate that beta-amyloid (Aβ) plaque burden starts to be more severe around P180 (moderate disease stage) in female transgenics when compared to males and that aging aggravates this sex-specific difference. Furthermore, we show that female transgenics suffer from higher levels of neurovascular dysfunction around P180, resulting in impaired Aβ peptide clearance across the blood-brain-barrier at P360. Female transgenics show also higher levels of diffuse microgliosis and inflammation, but the density of microglial cells surrounding Aβ plaques is less in females. In line with this finding, testosterone compared to estradiol was able to improve microglial viability and Aβ clearance in vitro. The spatial memory of transgenics was in general poorer than in wildtypes and at P360 worse in females irrespective of their genotype. This difference was accompanied by a slightly diminished dendritic complexity in females. While all the above-named sex-differences emerged after the onset of Aβ pathology, kallikrein-8 (KLK8) protease levels were, as an exception, higher in female than in male brains very early when virtually no plaques were detectable. In a second step, we quantified cerebral KLK8 levels in AD patients and healthy controls, and could ascertain, similar to mice, higher KLK8 levels not only in AD-affected but also in healthy brains of women. Accordingly, we could demonstrate that estradiol but not testosterone induces KLK8 synthesis in neuronal and microglial cells. In conclusion, multiple features of AD are more pronounced in females. Here, we show for the first time that this sex-specific difference may be meditated by estrogen-induced KLK8 overproduction long before AD pathology emerges.

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Poor Oral Health Linked with Higher Risk of Alzheimer's Disease.

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Poor Oral Health Linked with Higher Risk of Alzheimer's Disease.

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