Table 3.

Association between Periodontitis and Neurodegenerative Diseases.

Types of Study	Finding
8,640 patients with dementia without prior periodontal disease and 8,640 individuals without dementia history	Dementia and AD were associated with a higher risk of periodontal disease dependent of age and independent of systemic confounding factors (Ma et al. 2022).
48 elderly cognitively normal subjects	Higher subgingival periodontal dysbiosis was significantly associated with reduced CSF amyloid β at both genera and species levels (Kamer et al. 2021).
5,396 cases of newly diagnosed PID, 10,792 cases without PID	Patients with PID had a higher risk of developing PD (adjusted hazard ratio = 1.431; 95% CI, 1.141–1.794; P = 0.002) (Chen et al. 2017).
Human cerebral cortex lysates of 3 AD and 6 control brains; CSF from 10 patients diagnosed with probable AD with mild to moderate cognitive impairment	Gingipains load were significantly higher in AD patients than control brains (P < 0.0001) and significantly correlated with tau pathology (P < 0.0001) and ubiquitin load (P < 0.0001) (Dominy et al. 2019).
4,765 newly diagnosed cases of PD, 19,060 without PD	Dental scaling decreases the development of PD (Chen et al. 2018).
74 PD patients and 74 controls	PD patients had weakened oral health status and reduced oral hygiene care (van Stiphout et al. 2018).
316 patients diagnosed with MS and 1,580 randomly selected controls	MS patients were 1.86 times (95% CI, 1.39–2.48) more likely to have previously diagnosed chronic periodontitis than controls after adjusting for variables (Sheu and Lin 2013).
153,165 PD participants with prescription for anti-PD medication	Competent dental care and toothbrush frequency significantly reduced risk of development of new-onset PD (Woo et al. 2020).
Young and middle-aged mice (control or infected) with live Porphyromonas gingivalis ATCC 33277 by oral gavage	P. gingivalis can impair spatial learning and memory, with significant increased inflammatory cytokines in brain tissues of middle-aged mice but not in young mice (P < 0.01) (Ding et al. 2018).
FVB/N mice and mutant LRRK2 mice (transgenic R1441G PD model) with and without oral gavage of P. gingivalis	P. gingivalis increased gut inflammation and permeability in PD mice. α-Synuclein was higher in the myenteric plexus of colon in P. gingivalis–treated PD mice (Feng et al. 2020).
Wild-type C57/BL6 mice with ligature	Periodontal inflammation-induced IL-6 led to neuroinflammation and disrupted the BBB (Furutama et al. 2020).
Young male Sprague-Dawley rats periodontitis models	Periodontitis induced by P. gingivalis–LPS led to neuroinflammation and impaired learning and memory in rats (Hu et al. 2020).
Periodontitis mice induced by oral application of Pg/gingipain and control	P. gingivalis/gingipain led to brain inflammation, neurodegeneration, and amyloid β production in wild-type mice (Ilievski et al. 2018).
Oral inoculation of P. gingivalis in APP-Tg AD mice	Periodontitis induced by bacterial infection exacerbated features of AD in transgenic mice (Ishida et al. 2017; Hao et al. 2022).
Ligature-induced periodontal disease on 5×FAD mice and wild-type mice	Ligature-induced periodontitis increased neuroinflammation in wild-type mice and disrupted the neuroinflammatory response in 5×FAD mice (Kantarci et al. 2020).
Oral administration of P. gingivalis 3×/wk for 1 mo in mice	P. gingivalis impaired cognition associated with gut dysbiosis, neuroinflammation, and glymphatic dysfunction (Chi et al. 2021).
MS mouse model received control, subcutaneous, or oral gavage of P. gingivalis	Infection with P. gingivalis had significantly greater maximal clinical scores of autoimmune encephalomyelitis compared to control (Polak et al. 2018).
CP induced with ligature and control	CP mice exhibited significant neuronal loss in cortex, reduction of synaptophysin in hippocampus and cortex, increase of proinflammatory cytokine levels, disruption of the BBB, gut microbiota dysbiosis, and systemic inflammation (Xue et al. 2020).

AD, Alzheimer’s disease; BBB, blood–brain barrier; CI, confidence interval; CP, chronic periodontitis; CSF, cerebrospinal fluid; IL-6, interleukin-6; LPS, lipopolysaccharide; MS, multiple sclerosis; PD, Parkinson’s disease; PID, periodontal inflammatory disease.