Effects of Tooth Loss and the Apolipoprotein E ɛ4 Allele on Mild Memory Impairment in the Fujiwara-kyo Study of Japan: A Nested Case-Control Study

Abstract

Background: Several studies have suggested that periodontal disease can exacerbate the pro-inflammatory status of the brain. Tooth loss is one of the alternative evaluation indices of periodontal disease. There are few data on the relationship between tooth loss and memory impairment, depending on the apolipoprotein E (APOE) ɛ4 genotype.Objective: To determine if tooth loss is associated with mild memory impairment (MMI) and if this association is modified by the presence of the APOE ɛ4 allele.Methods: A nested case-control study was conducted from 2007 to 2012 in Japan. Five hundred and thirty-seven Japanese subjects aged 65 years and over who were cognitively intact at baseline were analyzed. MMI at follow-up was evaluated.Results: The median number of teeth at baseline was significantly lower in MMI participants (n = 179) than in controls (n = 358) (MMI: median 21.0, interquartile range 10.0–25.0 versus controls: 24.0, 14.0–27.0). After adjustment for demographics, vascular risk factors, and APOE ɛ4 allele, the multivariate adjusted odds ratio (OR) of ≤8 teeth was 1.97 (95% confidence interval [CI], 1.13–3.44) compared to 25–32 teeth. Participants with both the presence of at least 1 APOE ɛ4 allele and ≤8 teeth had a higher risk of MMI compared with those with neither (OR, 2.82; 95% CI, 1.15–6.91). Those with either risk factor alone did not have a higher risk of MMI.Conclusions: A lower number of teeth is related to risk of MMI. This may be primarily true for those individuals with an APOE ɛ4 allele.

Dental deafferentation and brain damage: A review and a hypothesis

“…However, as the brain ages, the plasticity of the brain decreases [31,32], and it is theorized that further shocks to the brain's functions by major DDs that cause chronic dysfunctional or impaired mastication (such as the loss of strategic molars, generalized periodontal detachments and/or orthodontic management) may result in the brain's suffering varying degrees of impact in different areas. In the aging process, multiple major DDs and consequent effects may lead to blunted sensory perceptions [7–11], and cognitive and memory impairment in old age [12–30,41–53,63–65], thus contributing to the onset or aggravation of dementia or AD.…”

“…Several studies from the same group [21–23] indicate that tooth loss is positively associated with MMI, MCI and dementia, especially in those individuals carrying Lipo‐E alleles [23], and that the mental health of the subjects in question are significantly influenced by having a suboptimal number of teeth.…”

“…DD is shown by both animal and clinical researches to have a positive association with memory and cognitive status [12–30,41–53,63–65]. The conversion rate from MCI to dementia is reportedly 20–50% within 5 years [66,67].…”

“…Examples of DD include: Tooth loss, local and/or generalized periodontal detachment, improper operative or prosthetic restorations, and orthodontic managements and the unavoidable consequence of impaired mastication. These DDs may cause sensory and motor cortical reorganization [1–4], affect cerebral functional streams toward multisensory hubs [5,6], impair gustatory, auditory and olfactory perceptions [7–11], and result in memory and cognition impairment [12–30].…”

“…The greatest risk factor for cognitive decline and Alzheimer's disease in older adults is age itself [31,32]. Accumulating scientific evidence has indicated a correlation between DD and impaired brain functions such as memory loss, cognitive impairment, and even prodromes of AD and dementia [12–30]. A recent review of both animal trials and clinical research [33] has highlighted the causal relationship of mastication on cognitive functions.…”