Dental Carotid Cognitive Study

NCT03755362 | Terminated DMC

• 1 other identifier: HP-00082777
• Study Type: interventional
• Target: 26
• Locations: 1 country
• Sites: 1

Brief Summary

Periodontal Disease (PD) is present in 60+% of adults \>65 years and is associated with tobacco smoking, diabetes, and atherosclerosis that worsen inflammation, comorbidities common in older people with mild to moderate cognitive impairment (MCI). Older MCI patients are prone to poor oral hygiene and dental health, which if untreated worsens inflammation-mediated brain and nervous system function, and accelerates progression to dementia. Asymptomatic carotid artery stenosis (ACAS) is often a silent disease detected in only \~10% of older adults, and may have a strong association with MCI. This study examines the effects of intensive therapy for periodontitis on cognition in high-risk older people with ACAS. Results could highlight PD as a readily modifiable risk factor for dementia.

Conditions

Carotid Stenosis; Periodontitis; Mild Cognitive Impairment

Keywords

carotid stenosis cognitive function periodontitis

Outcome Measures

Primary Outcomes (1)

• Changes in performance on Montreal Cognitive Assessment (MoCA)

  The Montreal Cognitive Assessment (MoCA) is 30 item screening tool used to detect cognitive impairment. Score: 30 points (maximum), 0 points (minimum). Higher scores indicate better cognitive function. Differences in rate of change of MoCA score in those on intensive treatment for periodontitis and those receiving standard care.

  1 year

Secondary Outcomes (13)

• Presence of oral bacteria in saliva and dental plaque samples

  1 year

• Presence of bacteria in stool samples

  1 year

• Systemic inflammation

  1 year

• Change from baseline in Fluorodeoxyglucose Positron Emission Tomography (FDG-PET) Metabolic Measure of Standard Uptake Value Ratio (SUVR)

  1 year

• Changes in performance on Wechsler Adult Intelligence Scale (WAIS)-III Digit Span subtest

  1 year

Study Arms (2)

Standard treatment (control)

ACTIVE COMPARATOR

Dental evaluation and dental prophylaxis at baseline, 3, 6, and 9 months and standard oral hygiene instruction.

Procedure: Standard Treatment

Intensive Treatment

EXPERIMENTAL

Dental evaluation at baseline, 3, 6, and 9 months. Plus one or more sessions as needed at baseline of full mouth supra- and sub-gingival scaling and root planing, plus oral hygiene instruction. Additional sessions as necessary to remove remaining local factors and treat inflammation and bacteria overgrowth. Additional evaluations and therapy at 2 months or as needed based on therapeutic response. If bleeding on probing levels do not decrease to \<20% of sites following initial therapy or at subsequent visits, intermediate treatment visits will be scheduled. Each participant will be instructed to use half of a capful of 0.12% chlorhexidine twice a day during active treatment including two weeks beyond the treatment visit.

Procedure: Intensive Treatment

Interventions

Standard Treatment PROCEDURE

Dental evaluation at baseline, 3, 6, and 9 months.

Standard treatment (control)

Intensive Treatment PROCEDURE

Dental evaluation at baseline, 3, 6, and 9 months. Plus one or more sessions as needed at baseline of full mouth supra- and sub-gingival scaling and root planing, plus oral hygiene instruction. Additional sessions as necessary to remove remaining local factors and treat inflammation and bacteria overgrowth. Additional evaluations and therapy at 2 months or as needed based on therapeutic response. If bleeding on probing levels do not decrease to \<20% of sites following initial therapy or at subsequent visits, intermediate treatment visits will be scheduled. Each participant will be instructed to use half of a capful of 0.12% chlorhexidine twice a day during active treatment including two weeks beyond the treatment visit.

Intensive Treatment

Eligibility Criteria

• Age: 60 Years - 100 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age equal to or greater than 65 years.
• Body Mass Index 18-35 kg/m2
• Mild to moderate periodontitis
• Mild to moderate cognitive impairment on Montreal Cognitive Assessment (MoCA) -range greater than or equal to 17 and less than or equal to 26 (i.e., range from 17-26).
• Detectable carotid plaque and carotid artery stenosis \<70% as diagnosed by doppler ultrasound.
• Able to perform prescribed dental hygiene and travel to medical center as required to participate in the study.

You may not qualify if:

• Inability to provide informed consent.
• Subjects with inability to perform cognitive and other research testing
• Prior stroke, depression (CESD \>16), neurologic or psychiatric disease that would affect cognitive testing, participation, and compliance to the research study.
• Subjects requiring chronic treatment with systemic corticosteroids or other systemic immunosuppressive drugs or drugs that would affect the dental treatments in the protocol are excluded.
• Subjects requiring essential dental care (e.g., treatment for grossly decayed teeth, broken teeth, dental abscesses, peri-apical infections, other dental infections).
• Inability to perform FDG-PET due to renal disease (eGFR \<30 mL/min/1.75m2).
• Receiving anticoagulant therapy (Warfarin) with an INR greater than 3.3 at time of dental treatment or with a bleeding disorder, or other diseases that may interfere with dental therapy.
• Subjects with medical conditions that the clinicians feel would limit their ability to participate.

Sponsors & Collaborators

• University of Maryland: collaborator
• University of Maryland, Baltimore: lead
• Baltimore VA Medical Center: collaborator

Study Sites (1)

University of Maryland - Administrative Center

Baltimore, Maryland, 21201, United States

Location

Related Publications (11)

• Gorelick PB, Scuteri A, Black SE, Decarli C, Greenberg SM, Iadecola C, Launer LJ, Laurent S, Lopez OL, Nyenhuis D, Petersen RC, Schneider JA, Tzourio C, Arnett DK, Bennett DA, Chui HC, Higashida RT, Lindquist R, Nilsson PM, Roman GC, Sellke FW, Seshadri S; American Heart Association Stroke Council, Council on Epidemiology and Prevention, Council on Cardiovascular Nursing, Council on Cardiovascular Radiology and Intervention, and Council on Cardiovascular Surgery and Anesthesia. Vascular contributions to cognitive impairment and dementia: a statement for healthcare professionals from the american heart association/american stroke association. Stroke. 2011 Sep;42(9):2672-713. doi: 10.1161/STR.0b013e3182299496. Epub 2011 Jul 21.

  PMID: 21778438 BACKGROUND

• Smith JA, Das A, Ray SK, Banik NL. Role of pro-inflammatory cytokines released from microglia in neurodegenerative diseases. Brain Res Bull. 2012 Jan 4;87(1):10-20. doi: 10.1016/j.brainresbull.2011.10.004. Epub 2011 Oct 18.

  PMID: 22024597 BACKGROUND

• Leszek J, Barreto GE, Gasiorowski K, Koutsouraki E, Avila-Rodrigues M, Aliev G. Inflammatory Mechanisms and Oxidative Stress as Key Factors Responsible for Progression of Neurodegeneration: Role of Brain Innate Immune System. CNS Neurol Disord Drug Targets. 2016;15(3):329-36. doi: 10.2174/1871527315666160202125914.

  PMID: 26831258 BACKGROUND

• Miklossy J, McGeer PL. Common mechanisms involved in Alzheimer's disease and type 2 diabetes: a key role of chronic bacterial infection and inflammation. Aging (Albany NY). 2016 Apr;8(4):575-88. doi: 10.18632/aging.100921.

  PMID: 26961231 BACKGROUND

• Otomo-Corgel J, Pucher JJ, Rethman MP, Reynolds MA. State of the science: chronic periodontitis and systemic health. J Evid Based Dent Pract. 2012 Sep;12(3 Suppl):20-8. doi: 10.1016/S1532-3382(12)70006-4.

  PMID: 23040337 BACKGROUND

• Daulatzai MA. Cerebral hypoperfusion and glucose hypometabolism: Key pathophysiological modulators promote neurodegeneration, cognitive impairment, and Alzheimer's disease. J Neurosci Res. 2017 Apr;95(4):943-972. doi: 10.1002/jnr.23777. Epub 2016 Jun 27.

  PMID: 27350397 BACKGROUND

• Teixeira FB, Saito MT, Matheus FC, Prediger RD, Yamada ES, Maia CSF, Lima RR. Periodontitis and Alzheimer's Disease: A Possible Comorbidity between Oral Chronic Inflammatory Condition and Neuroinflammation. Front Aging Neurosci. 2017 Oct 10;9:327. doi: 10.3389/fnagi.2017.00327. eCollection 2017.

  PMID: 29085294 BACKGROUND

• Fouad A, Mongodin E, Hittle L, et al. Microbiome analysis of oral and atheromatous plaques in atherosclerotic patients. In: IADR General Session and Exhibition. 2014

  BACKGROUND

• Emery DC, Shoemark DK, Batstone TE, Waterfall CM, Coghill JA, Cerajewska TL, Davies M, West NX, Allen SJ. 16S rRNA Next Generation Sequencing Analysis Shows Bacteria in Alzheimer's Post-Mortem Brain. Front Aging Neurosci. 2017 Jun 20;9:195. doi: 10.3389/fnagi.2017.00195. eCollection 2017.

  PMID: 28676754 BACKGROUND

• Caminiti SP, Ballarini T, Sala A, Cerami C, Presotto L, Santangelo R, Fallanca F, Vanoli EG, Gianolli L, Iannaccone S, Magnani G, Perani D; BIOMARKAPD Project. FDG-PET and CSF biomarker accuracy in prediction of conversion to different dementias in a large multicentre MCI cohort. Neuroimage Clin. 2018 Jan 28;18:167-177. doi: 10.1016/j.nicl.2018.01.019. eCollection 2018.

  PMID: 29387532 BACKGROUND

• Ide M, Harris M, Stevens A, Sussams R, Hopkins V, Culliford D, Fuller J, Ibbett P, Raybould R, Thomas R, Puenter U, Teeling J, Perry VH, Holmes C. Periodontitis and Cognitive Decline in Alzheimer's Disease. PLoS One. 2016 Mar 10;11(3):e0151081. doi: 10.1371/journal.pone.0151081. eCollection 2016.

  PMID: 26963387 BACKGROUND

MeSH Terms

Conditions

Carotid Stenosis; Cognitive Dysfunction; Periodontitis

Condition Hierarchy (Ancestors)

Carotid Artery Diseases; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Arterial Occlusive Diseases; Vascular Diseases; Cardiovascular Diseases; Cognition Disorders; Neurocognitive Disorders; Mental Disorders; Periodontal Diseases; Mouth Diseases; Stomatognathic Diseases

Study Officials

• Brajesh K Lal, MD

  University of Maryland, Baltimore

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Study Principal Investigator

Model Details: This study will randomize 60 subjects ≥65 years old with asymptomatic carotid artery stenosis (ACAS), mild to moderate cognitive impairment and periodontitis. These 60 patients will be randomized to two groups (intensive vs. standardized periodontal treatment). As randomization will be computer generated, the likelihood of randomization to either group is 50:50.

Study Record Dates

• First Submitted: November 12, 2018
• First Posted: November 28, 2018
• Study Start: April 8, 2019
• Primary Completion: February 21, 2021
• Study Completion: February 25, 2021
• Last Updated: February 18, 2026

Record last verified: 2026-02

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)