Gum disease, especially the kind that is irreversible and causes tooth loss, may be associated with mild cognitive impairment and dementia 20 years later, according to a study published in the July 29, 2020, online issue of Neurology.
“We looked at people’s dental health over a 20-year period and found that people with the most severe gum disease at the start of our study had about twice the risk for mild cognitive impairment or dementia by the end,” said study author Ryan T. Demmer, Ph.D., M.P.H., of the University of Minnesota School of Public Health in Minneapolis.
“However, the good news was that people with minimal tooth loss and mild gum disease were no more likely to develop thinking problems or dementia than people with no dental problems.”
The study involved 8,275 people with an average age of 63 who did not have dementia at the start of the study.
The participants were assessed for mild cognitive impairment and dementia. Participants received a full periodontal exam that included measuring gum probing depth, amount of bleeding and recession.
Then participants were put into groups based on the severity and extent of their gum disease and number of lost teeth, with implants counting as lost teeth.
At the start of the study, 22% had no gum disease, 12% had mild gum disease, 12% had severe gum inflammation, 8% had some tooth loss, 12% had disease in their molars, 11% had severe tooth loss, 6% had severe gum disease, and 20% had no teeth at all.
A total of 4,559 people was assessed at the end of the study, when they had been followed for an average of 18 years.
Overall, 1,569 people developed dementia during the study, or 19%. This was the equivalent of 11.8 cases per every 1,000 person-years.
The study found that of the people who had healthy gums and all their teeth at the start of the study, 264 out of 1,826, or 14%, developed dementia by the end of the study. For those with mild gum disease, 623 out of 3,470, or 18%, developed dementia.
For participants with severe gum disease, 306 out of 1,368, or 22%, developed dementia. And 376 out of 1,611, or 23%, developed dementia in the group that had no teeth. This was equal to a rate of 16.9 cases per 1,000 person-years.
When looking at both mild cognitive impairment and dementia, the group with no teeth had about twice the risk compared to participants with healthy gums and all their teeth.
People with intermediate or severe gum disease, but who still had some teeth, had a 20% greater risk of developing mild cognitive impairment or dementia compared to the healthy group.
These risks were after researchers accounted for other factors that could affect dementia risk, such as diabetes, high cholesterol and smoking.
“Good dental hygiene is a proven way to keep healthy teeth and gums throughout your lifetime. Our study does not prove that an unhealthy mouth causes dementia and only shows an association.
Further study is needed to demonstrate the link between microbes in your mouth and dementia, and to understand if treatment for gum disease can prevent dementia,” Demmer said.
A limitation of the study is the fact that initial gum examinations were made when the participants had an average age of 63, and it is possible that cognitive decline might have been begun before the start of gum disease and tooth loss.
EPIDEMIOLOGY OF POOR ORAL HEALTH AND PERIODONTAL DISEASE
Poor oral health, including periodontitis, caries, edentulism, and infrequent preventive care, become more prevalent among older people8, 9.
Edentulism is a global health problem in the elderly with prevalence as high as 78% in some European countries; persons with low socioeconomic status are disproportionately affected10, 11.
Caries and periodontitis are thought to be two predominant causes of tooth loss, often co-occurring within individuals, and share several risk factors including poor oral hygiene, low socioeconomic status, and inattention to care.
However, of these oral health states, periodontitis is more common among adults and progresses with age.12, 13
Worldwide estimates in the prevalence of periodontitis vary, partly because of substantial heterogeneity in definitions of the disease14.
Clinical and serological markers of disease indicate that moderate to severe periodontitis may be prevalent in more than 50% of US adults.15, 16 Exposure to established periodontal pathogens appears to begin as early as at 2 years of age, with a large proportion of the population exposed by adolescence17, often by vertical and horizontal transmission patterns among family members.18
While clinical markers of periodontitis may vary with time or treatment, periodontal serum IgG levels typically remain stable.19
POOR DENTAL HEALTH AND CEREBROVASCULAR DISEASE
Prior to first explorations relating dental health to frank cognitive impairment, a number of studies explored the relationship between history of periodontal disease and incident stroke,20, 21 with associations identified as ranging from no adverse risk to more than double.
Epidemiological evidence supports an association between the level of serum antibodies to periodontal pathogens and stroke 22–24 and accelerated aortic atherogenesis,25 while high levels of colonization by specific periodontal pathogens has been associated with increased carotid artery intimal-medial thickness.26
To date, no treatment trials addressing mitigation of periodontal disease and incident stroke have been performed.
Many of the risk factors associated with cerebrovascular disease are also associated with dementia. For example, vascular risk factors27, 28 including diabetes mellitus,28–33 dyslipidemia,34 hypertension,35 atrial fibrillation,36 smoking,28, 37–39 hyperhomocysteinemia,40 and obesity41–45 have been associated with the development of dementia, including AD.
Up to 33% of dementia patients with AD pathology have concomitant stroke 46 and patients may be more likely to become demented when both AD pathology and cerebrovascular disease are present47, 48.
POOR DENTAL HEALTH AND COGNITIVE IMPAIRMENT
Poor oral hygiene
Inattention to oral health care may be a precursor to many oral health diseases and could be a longstanding habituation among individuals, or alternatively could change in advancing age for various reasons including impaired physical movements, with or without cognitive impairment being implicated.
In a subgroup of the Geriatric Multidisciplinary Strategy for the Good Care of the Elderly (Gems), drawn from a population of those aged 75 years and above in eastern Finland, AD was associated with both poor oral hygiene (OR=12.2 [1.9–77.0]) and poor denture hygiene (OR=2.9 [1.1–7.8]).49 In the Aichi Gerontological Evaluation Study (AGES) Project, among older Japanese aged 65 years and above, those without regular dental visits were more likely to have incident dementia (HR=1.44 [1.04–2.01 ]).50
Exploratory analyses within a small clinical trial examining the effect of dental care on incident pneumonia in a group of elderly nursing home residents demonstrated a 1.5 point significantly slower decline in Folstein Mini Mental Status Exam score after 2 years in oral care recipients51.
However, from this study one cannot determine whether the effect specifically related to the dental hygiene intervention, or was instead simply related to greater frequency of attention to general health needs in the intervention subjects.
Caries is the most common cause of tooth loss in younger patients and thought to be caused by acid-producing oral microbiota, in individuals with poor oral hygiene and frequent intake sugar-rich diet the context of chronic poor attention to dental hygiene.52, 53
In contrast to periodontitis, however, caries is not typically thought to cause a systemic host inflammatory response. Several case-control studies have identified caries in older adults and cross-sectional associations with impaired cognition; 54, 55 these findings have been corroborated in larger community based cohorts.
In the Gems cohort, caries was associated with Alzheimer disease (RR=2.8 [1.8–4.5] as well as non-AD dementia (RR=3.4 [1.9–6.4]);49 another Finnish cohort of older adults identified similar patterns of increased caries rates being associated with cognitive impairment.56
A case-control study of elderly Australians found that dementia patients were more likely to have declining oral health including worsening caries when followed longitudinally.57
Tooth loss reflects the end stage of a several oral diseases, alone or in combination, including caries, periodontal disease, and endodontic infections.
Thus, tooth loss is a marker of cumulative morbidity of pathologic oral inflammatory conditions including periodontitis, and has been associated with prevalent cognitive impairment in several cross-sectional studies.
In the Health Survey for England 2000, an association between edentulism and cognitive impairment among population aged 65 years and older was strong (OR=2.61 [1.49–4.28]), although it was primarily driven by community based subjects, as no relationship was identified among those residing in nursing homes.58
The Study of Health in Pomerania in northeast Germany suggested that women may be at greater risk for having tooth loss associated with prevalent cognitive impairment.59 Several studies drawn from Asian populations have found similar associations between tooth loss and prevalent cognitive impairment, including a small Japanese case-control study of late-life tooth loss.60
In the Fujiwara-kyo study, a large community-based study of persons aged 65 years and older, those with the fewest teeth had the highest risk of cognitive impairment (OR=1.71 [1.05–2.78]); in addition, there was a significant trend for fewer teeth predicting cognitive impairment.61
However, other cross-sectional studies exploring dental health and cognition have either failed to identify edentulism as a risk for dementia49 or found only a weak association with cognitive impairment.62
Several studies have identified tooth loss as a risk for incident cognitive impairment. In the VA Dental Longitudinal Study, community-dwelling men with tooth loss were more likely to have impaired cognitive test performance, with those over the age of 45 being more significantly affected.63
In the HARMONY Swedish twin registry, dementia was associated with mid-life tooth loss (OR=1.49 [1.14–1.95]).64 In the United States, in the Religious Orders Study, fewer teeth in adulthood were significantly associated with incident dementia (HR 2.2 (1.1–4.5).65 APOE-£4 appeared to be a significant effect modifier in this relationship, with impaired memory developing at a younger age among APOE-ε4 carriers, particularly those with fewer teeth in adulthood.66
Impaired chewing ability and dentures
Patients with tooth loss, even when given dentures, have inadequate chewing capacity (low masticatory efficiency); a reported maximum load on natural teeth during chewing is 8 to 15 kilograms 67 while a typical load by sustained dentures is less than 2 kilograms.68
In the Swedish Panel Study of Living Conditions of the Oldest Old people (SWEOLD), a national sample of elders aged 77 and above, those with impaired chewing ability were more likely to be cognitively impaired (OR=1.72 [1.05–2.80]).69
In a prospective study of community dwelling elderly residents in Kwangju, South Korea, those persons with tooth loss and no dentures were most likely to develop dementia (OR=1.61, [1.02–2.49])70 and this was additionally corroborated in AGES (HR=1.85, [1.04–3.31]).50
Persons with low masticatory efficiency may have to adapt to eat diets low in fiber and essential micronutrients,71 and high in saturated fats and cholesterol, possibly due to ease of chewing these foods relative to fiber-rich foods.72
Such dietary changes, adaptive to low masticatory efficiency, could potentially increase the risk for stroke and dementia by making difficult adherence to diets thought to be protective against AD such as the “Mediterranean diet” 73, 74.
However, dietary habits may instead be confounded by lifelong influences of taste, economics, social norms, or unhealthy lifestyle decisions associated with tooth loss.75, 76 Micronutrient deficiencies, such as vitamin B12 and thiamine deficiency, may also develop as a result of edentulism 77 and may contribute to cognitive impairment (Fig 1).
Periodontitis is a chronic oral biofilm-mediated infection78, 79 that is strongly associated with tooth loss in adults. Several studies have associated periodontitis with prevalent and incident cognitive impairment.
In the VA Dental Longitudinal Study, for each tooth lost, pocket depth progression and alveolar bone loss progression were additionally associated with impaired cognitive test performance, with the strongest associations observed in individuals over 45 years of age.63
We identified a cross-sectional association between a serological marker of a common periodontitis pathogen (Porphyromonas gingivalis) and poor cognitive test performance among patients aged >60 years in NHANES-III.80
Our group additionally identified serum antibodies to several periodontal pathogens were associated with incident AD in a complex relationship including adverse or protective risk, depending upon the pathogen studied.81
Serum antibodies to several other periodontal organisms have been identified as potential risk markers for AD and mild cognitive impairment.82
In an age-matched case-control study of AD patients and healthy elders, serum levels of TNF-alpha and IgG antibodies to periodontal bacteria discriminated between the two groups at the time of cognitive diagnosis.83
Pathophysiologic links between periodontitis and cognitive impairment
From a neuropathological standpoint, AD is a progressive neurodegenerative process initially related to accumulation of excess brain amyloid-beta (Aβ) protein and subsequent tau deposition84.
Amyloid metabolism is complex and is influenced by local and systemic host inflammatory mediators. These include interactions between advanced glycation end products (AGEs) and their receptor RAGE that affect transduction of extra-cellular Aβ and influx of vascular Aβ, leading to increased intracellular Aβ84.
Periodontitis is currently considered to impact overall health via complex mechanisms mediated through a state of enhanced systemic inflammation21.
Periodontitis is associated with both a local 85 and a systemic inflammatory response characterized by elevation in multiple serum cytokines including interleukin-1 (IL-1),86 IL-6,87, 88 C-reactive protein (CRP),87, 89 and TNF-alpha90–92 and generation of serum antibodies to common periodontal organisms15, 93.
Several hundred periodontal pathogens have been implicated in causing periodontal disease,94 although only a small fraction of these hundreds of pathogens are cultivable and have been demonstrably associated with establishing a progressively pathogenic milieu at the biofilm interface.78
Gingival tissues of patients with periodontitis express high levels of AGEs and RAGE95, and AGE-RAGE interactions are one of the key mechanisms underlying the observed accelerated periodontal tissue breakdown in patients with diabetes96.
Importantly, treatment of periodontitis has been associated with significant reduction in serum levels of IL-687, IL-6 soluble receptor97 and CRP98, and a substantial improvement in vascular endothelial function97, 99–101.
Thus, although several specific periodontal pathogens have been specifically studied in the relationship between periodontitis and stroke or cognitive impairment, it is more likely that downstream systemic inflammatory responses affect this relationship, rather than individual pathogens.
In addition to stroke, periodontitis has been associated with risk factors for cardiovascular disease25, 102–105 and diabetes.106–108 Risk factors for stroke and dementia, including diabetes,109, 110 obesity,111 and smoking112 have a similar systemic inflammatory profile to periodontitis,112, 113 suggesting that inflammatory markers may contribute to a final common pathway of impaired cognition, perhaps mediated through a cascade of atherogenesis114, 115 related to systemic inflammation.113
Interestingly, high levels of CRP have also been reported to act as an effect modifier of the association between carriage of the APOE e4 allele and memory impairment in patients without dementia.116