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The aim of this study was to analyse the possible relationship between periodontal inflammation and Alzheimer's disease and to investigate the role of blood parameters in this relationship.
This retrospective case-control study will include individuals who were clinically and radiographically examined, diagnosed with periodontal disease, read and signed informed consent forms between March 2022 and July 2025 at the Periodontology Departments of Bezmialem Vakif University, Uskudar University and Bolu Abant Izzet Baysal University Faculty of Dentistry.
In this study, two groups will be formed as a case group consisting of individuals with periodontitis diagnosed with probable Alzheimer's disease according to NINCDS-ADRDA and DSM-V diagnostic criteria and a control group consisting of individuals with periodontitis only.
Patients who underwent periodontal evaluations at six sites per tooth, with the following parameters recorded-plaque percentage, probing pocket depth, percentage of bleeding on probing, clinical attachment level, number of teeth, and periodontal inflamed surface area (PISA)-will be included in the study.
Compliance with the inclusion and exclusion criteria will be verified through patient files and digital records. In individuals with a probable diagnosis of Alzheimer's disease according to NINCDS-ADRDA and DSM-V diagnostic criteria, disease stage as determined by the Clinical Dementia Rating scale and Standardized Mini-Mental Test (SMMT) scores will also be recorded.
Hematological data will be obtained from patients' recorded complete blood count test results and the following parameters will be utilized:
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Case group | Periodontitis with Alzheimer's disease |
| |
| Control group | Periodontitis without Alzheimer's disease |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Complete Blood Count Test | Diagnostic Test | Complete blood count test provides data on total white blood cell count, neutrophil count, neutrophil percentage, lymphocyte count, lymphocyte percentage, monocyte count, monocyte percentage, eosinophil count, eosinophil percentage, basophil count, basophil percentage, platelet count, platelet distribution width (PDW), mean platelet volume (MPV), plateletcrit (PCT), erythrocyte count, hemoglobin, hematocrit (HCT), mean corpuscular volume (MCV), mean corpuscular hemoglobin (MCH), mean corpuscular hemoglobin concentration (MCHC) and red blood cell distribution width (RDW). In addition, neutrophil-lymphocyte ratio (NLR), monocyte-lymphocyte ratio (MLR), platelet-leukocyte ratio (PLR), Pan-Immune-Inflammation Value (PIV), Systemic Immune-Inflammation Index (SII), Hemoglobin-to-Red Cell Distribution Width Ratio (HRR) values are also formulated from these parameters. |
| Measure | Description | Time Frame |
|---|---|---|
| Probing pocket depth | Measurement of the depth of a sulcus or periodontal pocket determined by measuring distance from a gingival margin to the base of the sulcus or pocket with a calibrated periodontal probe. | Baseline |
| Bleeding on probing (BOP) | The number obtained by dividing the sum of the positive areas by the sum of the examined areas is multiplied by 100 and the value obtained is expressed as the percentage of bleeding at probing (BOP%). | Baseline |
| Periodontal inflammatory surface area (PISA) | It is the calculation of the area of ulcerated periodontal pockets showing bleeding on probing based on the periodontal epithelial surface area. | Baseline |
| Measure | Description | Time Frame |
|---|---|---|
| Clinical attachment level | Clinical attachment level (CAL) is a more reliable indicator of periodontal support around a tooth than probing depth alone, as it is measured from a fixed anatomical landmark-the cementoenamel junction (CEJ)-which remains constant over time. Calculating CAL requires two measurements: the distance from the gingival margin to the CEJ and the probing depth. In cases of gingival recession, CAL is calculated by adding the probing depth to the distance from the gingival margin to the CEJ. In cases of gingival overgrowth, CAL is determined by subtracting the distance from the gingival margin to the CEJ from the probing depth. |
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Inclusion Criteria:
Exclusion Criteria:
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Individuals with periodontitis with Alzheimer's disease (Case group), Individuals with periodontitis without Alzheimer's disease (Control group)
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| Name | Affiliation | Role |
|---|---|---|
| OZLEM GELISIN | Dr. Sadi Konuk Training and Research Hospital | Study Chair |
| AHMET AYDOGDU | Istanbul Galata University | Study Chair |
| SADIYE GUNPINAR | Bezmialem Vakif University | Study Chair |
| ZEYNEP AKGUL | Abant Izzet Baysal University | Study Chair |
| KUBRA KARADURAN | Uskudar University | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Bolu Abant Izzet Baysal University | Bolu | Turkey (Türkiye) | ||||
| Bezmialem Vakif University |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 36860868 | Background | Wang RH, Wen WX, Jiang ZP, Du ZP, Ma ZH, Lu AL, Li HP, Yuan F, Wu SB, Guo JW, Cai YF, Huang Y, Wang LX, Lu HJ. The clinical value of neutrophil-to-lymphocyte ratio (NLR), systemic immune-inflammation index (SII), platelet-to-lymphocyte ratio (PLR) and systemic inflammation response index (SIRI) for predicting the occurrence and severity of pneumonia in patients with intracerebral hemorrhage. Front Immunol. 2023 Feb 13;14:1115031. doi: 10.3389/fimmu.2023.1115031. eCollection 2023. | |
| 31902361 |
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|
| Periodontal examinations | Diagnostic Test | With periodontal evaluation, plaque percentage, probing pocket depth, percentage of bleeding on probing, clinical attachment level, number of teeth, periodontal inflammatory surface area (PISA) parameters are recorded. |
|
| Clinical Dementia Rating scale | Diagnostic Test | Stage I: mild Alzheimer's disease, Stage II: moderate Alzheimer's disease, Stage III: severe Alzheimer's disease |
|
| Standardized Mini-Mental Test | Diagnostic Test | Cognitive status is assessed with the Standardized Mini-Mental Test. |
|
| Baseline |
| Plaque percentage | The presence or absence of plaque is determinant, recorded as (+) in the presence of plaque or (-) in the absence of plaque, and the percentage of the entire mouth affected by plaque is expressed as a percentage (P%). | Baseline |
| Number of teeth | Recording the number of teeth present | Baseline |
| White blood cell count | White blood cell (WBC) count measures the total number of leukocytes in peripheral blood, usually expressed as cells per microliter (cells/µL). WBC is essential for evaluating immune status, infections, and inflammatory conditions. | Between baseline and -6th month |
| Neutrophil count | Neutrophil count measures the absolute number of neutrophils in peripheral blood, typically expressed as cells per microliter (cells/µL). Neutrophils play a critical role in innate immune defense, especially against bacterial infections. | Between baseline and -6th month |
| Lymphocyte count | Lymphocyte count measures the absolute number of lymphocytes in peripheral blood, typically expressed as cells per microliter (cells/µL). Lymphocytes are essential for adaptive immune responses and immune memory. | Between baseline and -6th month |
| Monocyte count | Monocyte count measures the absolute number of monocytes in peripheral blood, typically expressed as cells per microliter (cells/µL). Monocytes are key cells in immune response, inflammation, and tissue repair. | Between baseline and -6th month |
| Eosinophil count | Eosinophil count measures the absolute number of eosinophils in peripheral blood, typically expressed as cells per microliter (cells/µL). Eosinophils are involved in allergic responses and parasitic infections. | Between baseline and -6th month |
| Basophil count | Basophil count measures the absolute number of basophils in peripheral blood, usually expressed as cells per microliter (cells/µL). Basophils are involved in allergic and inflammatory responses. | Between baseline and -6th month |
| Percentage of neutrophils | The percentage of neutrophils represents the proportion of neutrophils among total white blood cells, expressed as a percentage (%). Neutrophils are key players in innate immune response and bacterial defense. | Between baseline and -6th month |
| Percentage of lymphocytes | The percentage of lymphocytes indicates the proportion of lymphocytes among total white blood cells, expressed as a percentage (%). Lymphocytes are essential for adaptive immune responses. | Between baseline and -6th month |
| Percentage of monocytes | The percentage of monocytes represents the proportion of monocytes among total white blood cells, expressed as a percentage (%). Monocytes play a critical role in immune response, inflammation, and tissue repair. | Between baseline and -6th month |
| Percentage of eosinophils | The percentage of eosinophils indicates the proportion of eosinophils among total white blood cells, expressed as a percentage (%). Eosinophils play key roles in allergic responses and parasitic infections. | Between baseline and -6th month |
| Percentage of basophils | The percentage of basophils represents the proportion of basophils among total white blood cells, usually expressed as a percentage (%). Basophils are involved in allergic and inflammatory responses. | Between baseline and -6th month |
| Platelet count (PLT) | Platelet count (PLT) measures the number of platelets in a given volume of blood, expressed in thousands per microliter (×10³/μL). It is essential for assessing clotting function, bleeding disorders, and inflammatory status. | Between baseline and -6th month |
| Platelet distribution width (PDW) | Platelet Distribution Width (PDW) measures the variability in platelet size, reflecting platelet heterogeneity. It is used to assess platelet activation, production disorders, and systemic inflammatory conditions. | Between baseline and -6th month |
| Mean platelet volume (MPV) | Mean Platelet Volume (MPV) measures the average size of platelets in the blood and is expressed in femtoliters (fL). It reflects platelet activation and production and is used to assess platelet-related disorders and systemic inflammation. | Between baseline and -6th month |
| Plateletcrit (PCT) | Plateletcrit (PCT) represents the volume percentage of platelets in the blood and is calculated by multiplying the platelet count by the mean platelet volume. It reflects platelet mass and is used to assess platelet-related disorders and systemic inflammatory status. | Between baseline and -6th month |
| Red blood cell count | Red blood cell (RBC) count measures the number of erythrocytes in a given volume of blood, typically expressed in million cells per microliter (×10⁶/μL). It is used to assess oxygen transport capacity, anemia, and overall hematologic health. | Between baseline and -6th month |
| Hemoglobin (Hb) | Hemoglobin is the iron-containing protein in red blood cells responsible for transporting oxygen throughout the body. Hemoglobin concentration is measured in g/dL and is commonly used to assess anemia and systemic health status. | Between baseline and -6th month |
| Hematocrit (HCT) | Hematocrit (HCT) represents the percentage of whole blood volume occupied by red blood cells. It is used to evaluate oxygen-carrying capacity, anemia status, and hydration level. | Between baseline and -6th month |
| Mean corpuscular volume (MCV) | Mean Corpuscular Volume (MCV) indicates the average size of red blood cells and is expressed in femtoliters (fL). It is used to classify types of anemia. | Between baseline and -6th month |
| Mean corpuscular hemoglobin (MCH) | Mean Corpuscular Hemoglobin (MCH) represents the average amount of hemoglobin per red blood cell. It is commonly used to classify types of anemia. | Between baseline and -6th month |
| Mean corpuscular hemoglobin concentration (MCHC) | Mean Corpuscular Hemoglobin Concentration (MCHC) reflects the average concentration of hemoglobin in red blood cells and is expressed in g/dL. It is used to assess anemia types. | Between baseline and -6th month |
| Red blood cell distribution width (RDW) | Red Cell Distribution Width (RDW) reflects the variability in size of circulating red blood cells. It is considered a potential marker of inflammation, oxidative stress, and chronic disease burden. | Between baseline and -6th month |
| Neutrophil-to-lymphocyte ratio (NLR) | The neutrophil-to-lymphocyte ratio (NLR) is calculated by dividing the absolute neutrophil count by the absolute lymphocyte count. It serves as a marker of systemic inflammation and immune system balance | Between baseline and -6th month |
| Monocyte-to-Lymphocyte Ratio (MLR) | Monocyte-to-Lymphocyte Ratio (MLR) is the ratio of monocyte count to lymphocyte count in peripheral blood. It is used as a marker of systemic inflammation and immune system balance in various diseases. | Between baseline and -6th month |
| Platelet-to-lymphocyte ratio (PLR) | The platelet-to-lymphocyte ratio (PLR) is a systemic inflammation marker calculated by dividing the absolute platelet count by the absolute lymphocyte count. | Between baseline and -6th month |
| Pan-immune inflammation value (PIV) | It is a biomarker that evaluates the immune system and inflammation together. PIV= (Neutrophils × Monocytes × Platelets) / Lymphocytes | Between baseline and -6th month |
| Systemic immune-inflammation index (SII) | It is a parameter reflecting systemic inflammation and immune response. SII= (Neutrophil × Platelet) / Lymphocyte | Between baseline and -6th month |
| Hemoglobin to erythrocyte ratio (HRR) | It shows the ratio between the haemoglobin level and the distribution width of red blood cells. HRR= Hemoglobin / RDW | Between baseline and -6th month |
| Standardized Mini-Mental Test (SMMT) | The SMMT is used to quantitatively assess cognitive status in Alzheimer's disease patients. The maximum score of the SMMT is 30, of which 10 points correspond to orientation questions, 3 points to recording memory, 5 points to attention and calculation, 3 points to recall and 9 points to language. | Baseline |
| Clinical Dementia Rating Scale | The Clinical Dementia Rating (CDR) Scale is used to stage different types of dementia, especially Alzheimer-type dementia. Stage I: Mild, Satege II: Moderate, Stage III: Severe | Baseline |
| Istanbul |
| Turkey (Türkiye) |
| Uskudar University | Istanbul | Turkey (Türkiye) |
| Background |
| An P, Zhou X, Du Y, Zhao J, Song A, Liu H, Ma F, Huang G. Association of Neutrophil-Lymphocyte Ratio with Mild Cognitive Impairment in Elderly Chinese Adults: A Case-control Study. Curr Alzheimer Res. 2019;16(14):1309-1315. doi: 10.2174/1567205017666200103110521. |
| 38627719 | Background | Zhou C, Liu Y, Bai J, Luo Y, Song J, Feng P. Mean platelet volume is associated with periodontitis: a cross-sectional study. BMC Oral Health. 2024 Apr 16;24(1):461. doi: 10.1186/s12903-024-04223-8. |
| 32027386 | Background | Leira Y, Carballo A, Orlandi M, Aldrey JM, Pias-Peleteiro JM, Moreno F, Vazquez-Vazquez L, Campos F, D'Aiuto F, Castillo J, Sobrino T, Blanco J. Periodontitis and systemic markers of neurodegeneration: A case-control study. J Clin Periodontol. 2020 May;47(5):561-571. doi: 10.1111/jcpe.13267. Epub 2020 Mar 12. |
| 39733506 | Background | Tosatti JAG, Pereira JD, Loures CMG, Fraga VG, Magalhaes CA, Eugenio RDAC, Guimaraes HC, Resende EPF, de Souza LC, Carvalho MDG, Caramelli P, Gomes KB. Complete blood count and systemic inflammation indices in individuals with Alzheimer's disease: A case-control study. J Clin Neurosci. 2025 Feb;132:111011. doi: 10.1016/j.jocn.2024.111011. Epub 2024 Dec 28. |
| ID | Term |
|---|---|
| D010510 | Periodontal Diseases |
| D010518 | Periodontitis |
| D000544 | Alzheimer Disease |
| ID | Term |
|---|---|
| D009059 | Mouth Diseases |
| D009057 | Stomatognathic Diseases |
| D003704 | Dementia |
| D001927 | Brain Diseases |
| D002493 | Central Nervous System Diseases |
| D009422 | Nervous System Diseases |
| D024801 | Tauopathies |
| D019636 | Neurodegenerative Diseases |
| D019965 | Neurocognitive Disorders |
| D001523 | Mental Disorders |
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