Research Article: Association between chronic periodontitis and the risk of Alzheimer’s disease: a retrospective, population-based, matched-cohort study

Date Published: August 8, 2017

Publisher: BioMed Central

Author(s): Chang-Kai Chen, Yung-Tsan Wu, Yu-Chao Chang.

http://doi.org/10.1186/s13195-017-0282-6

Abstract

Although recent short-term cross-sectional studies have revealed that chronic periodontitis (CP) may be a risk factor for increased cognitive impairment in patients with Alzheimer’s disease (AD), systematic reviews and long-term longitudinal studies have provided less clear evidence regarding the relationship between CP and AD. Therefore, we conducted a retrospective cohort study using the National Health Insurance Research Database (NHIRD) of Taiwan to determine whether patients with CP are at increased risk of developing AD.

We conducted a retrospective matched-cohort study using the NHIRD of Taiwan. We identified 9291 patients newly diagnosed with CP between 1997 and 2004. A total of 18,672 patients without CP were matched to the patient cohort according to sex, age, index year, co-morbidity and urbanisation level. Cox proportional hazards regression analyses were performed to evaluate the subsequent risk of AD.

Patients with CP had a higher prevalence of hyperlipidaemia, depression, traumatic brain injury and co-morbidities, as well as higher urbanisation levels, than those in the unexposed cohort (all p < 0.01). At the final follow-up, totals of 115 (1.24%) and 208 (1.11%) individuals in the CP exposed and unexposed groups, respectively, had developed AD. Patients with 10 years of CP exposure exhibited a higher risk of developing AD than unexposed groups (adjusted HR 1.707, 95% CI 1.152–2.528, p = 0.0077). Our findings demonstrate that 10-year CP exposure was associated with a 1.707-fold increase in the risk of developing AD. These findings highlight the need to prevent progression of periodontal disease and promote healthcare service at the national level.

Partial Text

Alzheimer’s disease (AD) is a neurodegenerative disease characterised by progressive cognitive decline and memory loss, inevitably leading to complete loss of mental faculties and death [1]. AD is the most common cause of dementia in older adults [2–5]. Furthermore, due to increasing life expectancy and lifestyle changes, recent projections have indicated that 1 in 85 individuals will be diagnosed with AD by 2050 [6].

The baseline characteristics of the study sample are presented in Table 1. Patients with CP had a higher prevalence of hyperlipidaemia, depression and traumatic brain injury, as well as a CCI score and urbanisation level, than the unexposed cohort (all p < 0.01). The mean ages and follow-up times for the exposed and unexposed cohorts were 54.1 ± 10.5 vs. 54.2 ± 10.5 years and 11.9 ± 2.6 vs.12.2 ± 2.6 years, respectively.Table 1Demographic characteristics of the study cohort at baselineVariableTotalChronic periodontitisp valueWithWithoutn%n%n%Total27,963100929110018,672100Sex Female13,11946.92435146.83876846.960.8402 Male14,84453.08494053.17990453.04Age, years 50–5913,94749.88463849.92930949.860.9705 60–69885331.66294531.70590831.64 ≥70516318.46170818.38345518.50Hypertension No665423.80225124.23440323.580.2314 Yes21,30976.20704075.7714,26976.42Hyperlipidaemia No21,65177.43693574.6414,71678.81<0.0001 Yes631222.57235625.36395621.19Chronic kidney disease No17,24361.66569761.3211,54661.840.4009 Yes10,72038.34359438.68712638.16Depression No23,28383.26761982.0015,66483.89<0.0001 Yes468016.74167218.00300816.11Stroke No21,31676.23708176.2114,23576.240.9652 Yes664723.77221023.79443723.76Diabetes mellitus No14,54552.02462749.8991853.12<0.0001 Yes13,41847.98466450.2875446.88Traumatic brain injury No22,51780.52756281.3914,95580.090.0099 Yes544619.48172918.61371719.91CCI score 017,03260.91642369.1310,60956.82<0.0001 1782627.99220623.74562030.10 2310511.106627.13244313.08 ≥316856.034995.3711866.35Urbanisation level 1289610.368909.58200610.74<0.0001 2367513.14121913.12245613.15 319,70770.48668371.9313,02469.75CCI Charlson comorbidity index The present study is the first nationwide population-based matched-cohort study to demonstrate that patients with 10-year CP exposure exhibit an increased risk of developing AD (adjusted HR 1.707), regardless of co-morbidities, CCI score or urbanisation level. The prevalence of AD significantly increases with age, although AD in general is more common in women than in men [3]. AD is characterised by salient inflammatory features, microglial activation and increased levels of pro-inflammatory cytokines, which contribute to the inflammatory status of the central nervous system [37]. As a low-grade systemic disease, CP may involve the slow release of pro-inflammatory cytokines and CRP into the systemic circulation. This low-grade inflammation is thought to impact general systemic health and exacerbate other systemic disorders [38]. Therefore, CP may be a significant source of covert peripheral inflammation within the general population. Periodontitis has a tendency to infiltrate the systemic circulation with inflammatory mediators, thereby resulting in systemic disease. Researchers have proposed that periodontitis can lead to progression of AD by further increasing levels of pro-inflammatory cytokines and can lead to the invasion of micro-organisms from the dental plaque biofilm into the brain [28]. Moreover, these pro-inflammatory cytokines may penetrate the blood-brain barrier and induce neurodegenerative changes that ultimately influence the development of AD [26]. In the present study, we observed a significant correlation between CP and AD only after the 10-year follow-up for the initial diagnosis of CP. This finding supports the notion that pro-inflammatory factors due to CP may slowly and progressively induce neurodegenerative changes that lead to the development of AD. However, further study is required to verify this hypothesis. Our findings demonstrate that 10-year CP exposure was associated with a 1.707-fold increase in the risk of developing AD. These findings highlight the need to prevent progression of periodontal disease and promote healthcare services at the national level.   Source: http://doi.org/10.1186/s13195-017-0282-6

 

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