Clinical and Bacterial Markers of Periodontitis are Associated with Alzheimer’s Disease

by | Dec 15, 2020 | 2020, Alzheimer's Disease, Brain Health, Oral Health

Written by Joyce Smith, BS. This large retrospective study examines the association between periodontal pathogens and the incidence of Alzheimer’s disease (AD), AD mortality, and incident all-cause dementia.

dentist - oral healthDementia affects 4.7% of adults aged 60 and older 1 and increases annually by 4.6-7.7 million cases ) 1,2.  Approximately 60-80% of dementia is AD, a progressive neurodegenerative disorder characterized by memory loss, impaired cognition and Aß amyloid deposits in the brain 3. Approximately 54% of AD risk is due to genetic markers for late onset AD (such as ApoE4) as well as several modifiable risk factors such as low education, smoking, physical inactivity, depression, physical inactivity, depression, mid-life obesity, hypertension, and type 2 diabetes 4.

The Beydoun research team explored 5 potential associations of clinical periodontal disease with causes of AD dementia and mortality among US middle-aged and older adults. They linked data on participants from the third National Health and Nutrition Examination Surveys (NHANES III, 1988–1994), to the National Death Index and to Medicare data through January 1, 2014, comparing different age groups of more than 6000 participants at baseline and following them up for 26 years. Primary outcome was AD mortality. Participants (aged 45 years and older) were examined for signs of dental disease including clinical attachment loss (AL, a measure of cumulative exposure) and probing pocket depth (PPD, a measure of periodontitis) and had blood tests for bacterial periodontal markers. Serum immunoglobulin G (IgG) titers were used to identify antibodies against 19 oral bacteria to determine an association of AD with an AD diagnosis or mortality or any type of dementia.

Data analysis revealed that AD dementia, all-cause dementia and AD mortality reached 18%, 38% and 3% respectively in the 65+ age group. This group included older women and more widowed women of non-hispanic white race, smaller household size, and participants with larger AL and PPD and greater tooth loss. Periodontal pathogens were inversely associated with age. Socioeconomic status was associated with younger age; however, age was directly associated with better diet, reduced physical activity, smoking, drug use, less obesity, decreased vitamin D and increased folate, vitamins A and E, carotenoids and ferritin levels.  P. gingivalis was associated with an increased dementia risk particularly in women (P=0.004) and among individuals aged 55 or 65 years (p=0.010) at baseline, but only marginally associated with an increase in AD mortality in the 65+ age group. After additional multiple testing, evidence pointed to an association of PPD (but not AL) with incident AD among older adults, but for incident AD risk among men, researchers found the association was weak.

Mechanisms linking periodontal disease (Pd) and or pathogens to cognitive impairment and dementia are thought to involve the spread of bacterial pathogens from mouth to bloodstream and other bodily organs where toxins produce oxidative stress that damages the vascular system and leads to atherosclerotic disease, dementia and stroke 6. Inflammatory mediators of PD, such as cytokines, chemokines and prostaglandins trigger brain inflammation to contribute to AD 7. P. gingivalis secretes gingipains that inactivate antimicrobial and anti-inflammatory activities, inducing edema and bleeding of gums to further invade immune cells, increase inflammation and block immune response 8. The resulting inflammatory fluids function as a nutrient source (iron) 9 that supports bacterial growth. Finally, residual confounding bias, such as the role of the genetic risk factor ApoE4 known to be involved in early onset AD, cannot be excluded.

The evidence presented in this study that an association exists between Pd and AD, and that it increases with age, calls for a randomized controlled trial to further clarify the use of periodontal treatment to prevent or offset the progression of AD and other neurodegenerative disorders.

Source: Beydoun, May A., Hind A. Beydoun, Sharmin Hossain, Ziad W. El-Hajj, Jordan Weiss, and Alan B. Zonderman. “Clinical and Bacterial Markers of Periodontitis and Their Association with Incident All-Cause and Alzheimer’s Disease Dementia in a Large National Survey.” Journal of Alzheimer’s Disease Preprint (2020): 1-16.

© 2020 – IOS Press and the authors. All rights reserved

Posted December 15, 2020.

Joyce Smith, BS, is a degreed laboratory technologist. She received her bachelor of arts with a major in Chemistry and a minor in Biology from  the University of Saskatchewan and her internship through the University of Saskatchewan College of Medicine and the Royal University Hospital in Saskatoon, Saskatchewan. She currently resides in Bloomingdale, IL.

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