Table 1.

Characteristics of Included Studies

Study	Country	Case Samples	Controls	Baseline Mean-Age	Gender	Study type	Measure used for P. gingivalis	Measure used for AD	Follow-up	Quality Assessment
(Noble et al., 2014) [42]	USA (Manhattan)	110 incident AD cases	109 without incident CI at last follow-up	Cases: 79 Controls: 72	67.8% Female	Case-cohort study	Serum IgG AB levels by checkboard immunoblotting	Series of neurological tests CARE- Diagnostic Interview	5 years	11/14 (79%)
(Ide et al., 2016) [40]	UK (South Hampton)	22 mild/moderate AD Patients with PD	37 mild AD Patients w/out PD	Cases: 74.9 Controls: 79.4	49.2% Female	Observational cohort study for 6 months	Venous blood sample for CRP, pro-cytokine TNFα, IL10, and AB to PG. Number of teeth and full periodontal chart for presence or absence of periodontitis	NINCDS-ARDRA1 ADAS-cog2 sMMSE	6 months	10/14 (71%)
(Poole et al., 2013) [10]	UK (New Castle)	10 AD brain samples	10 Non-AD brain samples	Cases: 80.2 Controls: 74.8	N/A	Random case-control	Immunolabelling and immunoblotting with anti-PG	Confirmed AD brain samples	N/A3	7/11 (64%)
(Sparks Stein et al., 2012) [43]	USA (University of Kentucky)	35 developed AD. (46 developed MCI, 81 in total)	77 cognitively intact	Cases: 74.1 (for AD) Controls: 70	Cases: 74.3% Female Control: 58.4% Female	case-control study nested within a cohort study.	Venous blood evaluation for levels of IgG AB to the oral bacteria	NINCDS-ARDRA1 McKann et al. Criteria: MMSE	Cases: 9.6–9.8 years Controls: 12.5 years	8/12 (67%)
(Laugisch et al., 2018) [41]	Germany	20 AD patients	20 DEM-noAD5 patients	Cases: 58.3 Controls: 61.1	Cases: 55% Female Control: 40% Female	pilot observational study	CSF by lumbar puncture Blood serum Full clinical periodontal examination Subgingival biofilm sample and gingival crevicular fluid	AD by:NIAA (2011) guideline4, MMSE CSF for biomarkers MRI CERAD	N/A1	8/12 (67%)
(Kamer et al., 2009) [44]	USA (New York)	18 AD patients	16 cognitively normal	Cases: 40–65 (n = 2), 66–79 (n = 6), >  80 (n = 10) Controls: 40–65 (n = 7), 66–79 (n = 6),>80	Cases: 78% Female Control: 94% Female	Longitudinal case study	Fasting plasma for IgG AB and cytokine levels APOE genotyping using frozen whole blood.	NINCDS-ARDRA1 DSM-IV MMSE	N/A3	8/12 (67%)

IgG, immunoglobulin; AD, Alzheimer’s disease; TD, Treponema denticola; TF, Treponema forsythia; PG, Porphyromonas gingivalis; AB, antibody; sMMSE, standardized Mini-Mental Examination; LPS, lipopolysaccharides; MRI, magnetic resonance imaging; CSF, cerebrospinal fluid; APOE, Apolipoprotein E; CERAD, Consortium to Establish a Registry for Alzheimer’s Disease; DSM-IV, Diagnostic and Statistical Manual for Mental Diseases- 4th Edition. ¹NINCDS-ADRDA National Institute of Neurological and Communicative Disorders and Stroke and the Alzheimer’s Disease and Related Disorders Association. One of the most commonly used criteria in the diagnosis of Alzheimer’s disease [70]. ²ADAS-COG, Alzheimer’s Disease Assessment Scale-cognitive subscale. ³Not Applicable or available. ⁴National Institutes of Health and the Alzheimer’s Association Guidelines published in 2011. It includes new revised diagnostic clinical criteria for Alzheimer’s disease. The new guidelines include a deeper understanding of the early stages of the disease [71]. ⁵In the study by Laugisch et al. [41], the controls used were patients diagnosed with dementing diseases other than Alzheimer’s disease.