Effects of Tooth Loss and Apolipoprotein E ɛ4 Allele on Mild Memory Impairment

The incidence of Alzheimer’s disease and dementia are increasing globally. Research has identified an association between inflammation in the body and cognitive decline. Hence, researchers have begun evaluating whether modifying behaviors associated with inflammation in the body may be beneficial in reducing the incidence of mild cognitive impairment. The current study focused on periodontal disease as a possible modifiable mechanism for reducing cognitive decline. Periodontal disease, a chronic inflammatory condition in the mouth caused by gram-negative anaerobic bacteria, is associated with Aβ load (plaques found in the brain of Alzheimer’s patients). The Apolipoprotein E ɛ4 (APOE ɛ4) allele enhances the Aβ-induced inflammatory response and compromises the integrity of the blood brain barrier. Thus, the presence of periodontal disease and an APOE ɛ4 allele may impact cognitive function.

Having a lower number of teeth was associated with mild memory impairment (MMI) in a community dwelling cohort of Japanese men and women aged >65.1 The combined effect of having at least one APOE ɛ4 allele and a lower number of teeth was significant. The results indicate that preventing tooth loss in adulthood, especially elderly individuals with the APOE ɛ4 allele may be important for preserving memory.

The population group for the study came from the Fujiwara-kyo study, which started in Japan in 2007. At baseline, the study population consisted of 3,696 cognitively intact, community dwelling men and women age 65 or over, who were independent and able to walk unassisted. At follow-up, 241 patients were classified as having MMI. Two controls were selected, with frequency matching for age and gender, for each MMI case. Some MMI cases were excluded due to no useable blood sample, not wanting to participate in gene analysis, or no suitable control match. Ultimately, the study consisted of 179 MMI patients and 358 controls.

Cognitive function was evaluated using self-reported activities of daily living, the Mini Mental State Examination (MMSE), recall test, and Geriatric Depression Scale. APOE ɛ4 presence was determined using blood testing. Dental examinations were conducted to count teeth, determine the health of the teeth (healthy, carious, or treated), and to determine depth of periodontal pockets. The mouth was divided into 6 regions and a region was evaluated if 2 or more teeth were present. Teeth were ranked as a code 3 if there was a periodontal pocket 4-5mm deep and a code 4 if the pocket was at least 6mm deep.

The median number of teeth at baseline in cases was 21 and controls was 24. Tooth loss at baseline was significantly associated with mild memory impairment. There was a significant interaction between APOE ɛ4 status and number of teeth, with participants having at least one APOE ɛ4 allele and <8 teeth at greater risk for MMI than those with neither. Having one risk factor alone (APOE ɛ4 allele or <8 teeth) did not result in a higher risk of MMI. There was no combined effect for APOE ɛ4 and code 4 periodontal disease.


  1. Okamoto N, Morikawa M, Amano N, et al. Effects of Tooth Loss and the Apolipoprotein E 4 Allele on Mild Memory Impairment in the Fujiwara-kyo Study of Japan: A Nested Case-Control Study. Journal of Alzheimer’s Disease. In press, accepted August 23, 2016.

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