Tooth loss and dementia incidence in later life
To the best of our knowledge, the current study is the first well-designed meta-analysis that compares dementia occurrence risk among residual teeth number groups in later life. The current meta-analysis found that dementia occurrence risk in the high residual teeth number group was lowered by approximately half compared to the low residual teeth number group. However, wide variations in observation period, dementia definition, and high residual teeth group definition between studies may have led to greater heterogeneity among main findings. Despite significant dementia incidence rates between high/low residual teeth number groups as presented by pooled OR (0.483), the absolute difference of dementia incidence rates between these two groups was relatively narrow (+ 686 per 100,000 persons in low residual teeth number group). This effect can be explained by Paganini-Hill et al. [
26], which had the largest number of study participants and yet had results, though with marginal significance, that ran counter to those of the meta-analysis (high residual tooth number group increased dementia incidence).
There are multiple possible mechanisms by which tooth loss can adversely affect cognitive function in later life. It has been suggested that masticatory stimulation with normal occlusion increases cerebral blood flow, activation of the cortical area, and increases levels of oxygen in blood [
22,
29]. Reciprocally, poor mastication decreases orofacial sensorimotor activity, which eventually results in an overall cognitive decline [
30].
The association between tooth loss and dementia occurrence may be confounded by biological and healthcare system factors. Advanced age is the strongest predictor of incidence for any type of dementia as replicated by the current analysis. This finding has been identified from an early meta-analysis, which also noted that elderly women had a higher rate of dementia incidence [
31]. However, recent studies on the progression from mild cognitive impairment to Alzheimer disease present conflicting results [
32,
33]. A gender difference was not identified in dementia incidence in our analysis.
A recent meta-analysis by Xu et al. [
34] found a dose-response relationship between alcohol use and dementia incidence. Modest alcohol consumption was associated with a decreased risk of dementia incidence while high alcohol consumption was associated with an increased risk of dementia incidence. Data collection of alcohol intake for the analyzed studies was not quantified except for Batty et al. [
10]; therefore, the lack of association between alcohol intake and dementia occurrence found in this meta-analysis could be explained by the mixed effects of modest and high-amount of alcohol consumption. Previous studies have supported that smoking is associated with dementia incidence [
35,
36]. The magnitude of the relationship between smoking and dementia incidence was effaced to the point of marginal non-significance in this analysis, but potential selection bias from heterogeneous data may have occurred.
Diabetes and hypertension are cardiovascular risk factors and, when these are uncontrolled over a long-period, they may lead to atherosclerosis, which in turn may reduce cerebral blood flow. This has been the main explanation for the wide spectrum of cognitive impairment, from mild cognitive impairment to vascular and Alzheimer’s dementia [
10,
37,
38].
Chewing with a removable denture is at least 30% to 40% less efficient than chewing with natural teeth [
39]. Denture use might not restore the entire masticatory function in elderly patients with tooth loss as much as implants do. Therefore, denture use may not maintain cerebral blood flow in patients with tooth loss [
40].
Regular dental care was associated with a decreased risk of dementia occurrence in meta-regression from 4 analyzed studies [
22,
23,
26,
27]. More than half of adults in the US faced at least partial tooth loss and had not received regular dental care [
41]. Except for Paganini-Hill et al. [
26], which found no association between regular dental care and dementia incidence, three studies were conducted in Japan. These studies found that regular dental care reduced dementia incidence. The different lifestyle and health care systems between Paganini-Hill et al. [
26] and the other three Japanese studies [
22,
23,
27] may explain the different effects of regular dental care on dementia incidence [
42]. For example, older Japanese adults might have more access to dental care through the Japanese Ministry of Health and Welfare initiated nationwide dental policy, the “80–20” campaign in effect since 1989 [
43], as well as through a universal long-term care insurance implementation that has been happening since 2001 [
44], which promotes regular dental care in later life. In a subgroup analysis, Asian studies found a greater association between tooth loss and dementia incidence while in Western studies, this association was diminished. This finding could be interpreted as possible interactions between healthcare systems (universal vs. non-universal delivery systems) and dental care access. Therefore, future comparative studies are urgently needed, to see whether a link between regular dental care and dementia incidence can be replicated in countries where different health care systems, universal vs. non-universal, have been adopted.
Education itself could create an additional reserve against clinical manifestations of dementia or educational attainment may be the result of having a greater reserve to begin with [
45]. This hypothesis has been proven by a serial of cohort [
46] and meta-analyses [
47]. Temporal trends in developed countries, higher levels of education attainment, and better control of cardiovascular risk factors are considered likely contributors to the declining dementia risk [
48,
49]. Although educational attainment is a powerful determinant of health among older adults, participation in lifelong learning, especially with a community-based approach, has a great potential to attenuate the relationship between tooth loss and dementia incidence [
50]. Community-based lifelong learning programs could enhance social networks, active engagement, and encourage regular participation in intellectually stimulating activities, which may delay the progression of cognitive decline even in older adults whose cognition has already started to decline [
51].
Strengths and limitations
A strength of the current study is that the analysis was based on cohort studies which are better able to feasibly explain dementia occurrence when compared to cross-sectional studies. Another strength is the application of a structured approach to literature search and quality assessment.
There are several limitations in this study. The oral cavity, particularly in chronic periodontal disease, can affect tooth loss [
20,
21,
52] and cognitive impairment [
53‐
55] by multiple plausible explanations [
7,
53]. Chronic inflammation as measured by blood inflammatory markers are, in turn, thought to play a central role in altering the inflammatory state within the brain via various microbial or cytokines activities [
54,
56‐
59]. The mediator role of chronic periodontal disease has not been measured in the original studies, therefore, the mediator effect of chronic periodontal disease between tooth loss and dementia could not be presented in the current analysis. Heterogeneity from differing observation times, cognitive assessments, and definitions of high and low residual teeth number groups could raise concerns of overgeneralization when these findings are applied to real practice. There is potential reverse causality due to long prodromal phase of dementia. Time-person analysis might adjust an issue resulting from potential reverse causality. In addition, a time-person analysis could not be applied due to the lack of data from studies except for the most recently published study, Takeuchi et al. [
22]. This analysis relied on counting residual teeth at the completion of each study. A mid-point analysis that may have provided more information of time-variable analysis could not be performed.