Clinical trial NCT03755362: Dental Carotid Cognitive Study
Official title: Treatment of Periodontitis to Prevent Dementia in Older Adults With Asymptomatic Carotid Artery Stenosis and Mild Cognitive Impairment
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: NA
Conditions: Carotid Stenosis
Mild Cognitive Impairment
Periodontitis
Keywords: carotid stenosis cognitive function periodontitis
Lead sponsor: University of Maryland, Baltimore
Sponsor class: OTHER
Collaborators: name: University of Maryland, College Park
name: Baltimore VA Medical Center
First posted: 2018-11-28
Enrollment: 26
Sex: ALL
Minimum age (years): 60
Maximum age (years): 100
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: 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.
Primary purpose: PREVENTION

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.

Detailed description: 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.

This pilot study examines the hypothesis that intensive treatment of PD (IPT) in older people with MCI and ACAS will attenuate their cognitive decline by reducing oral microbial-mediated inflammation and improving cerebrovascular endothelial function that contribute to neurodegeneration-associated dementia.

The aims are to determine the effects of intensive compared to control PD treatment (randomized: IPT vs. CPT) in 60 MCI subjects with ACAS and PD on 1) Cognitive function (Primary Outcome) and quality of life (Secondary Outcome), and 2) The potential mechanisms mediating these effects

Eligibility criteria: Inclusion Criteria:

* 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.

Exclusion Criteria:

* 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.

Primary outcomes:
measure: Changes in performance on Montreal Cognitive Assessment (MoCA)
timeFrame: 1 year
Secondary outcomes:
measure: Presence of oral bacteria in saliva and dental plaque samples
timeFrame: 1 year
measure: Presence of bacteria in stool samples
timeFrame: 1 year
measure: Systemic inflammation
timeFrame: 1 year
measure: Change from baseline in Fluorodeoxyglucose Positron Emission Tomography (FDG-PET) Metabolic Measure of Standard Uptake Value Ratio (SUVR)
timeFrame: 1 year
measure: Changes in performance on Wechsler Adult Intelligence Scale (WAIS)-III Digit Span subtest
timeFrame: 1 year
measure: Changes in performance on Hopkins Verbal Learning Test
timeFrame: 1 year
measure: Changes in performance on Brief Visuospatial Memory test
timeFrame: 1 year
measure: Changes in performance on Trail Making Test (A+B)
timeFrame: 1 year
measure: Changes in performance on Controlled Oral Word Association Test
timeFrame: 1 year
measure: Changes in performance on Boston Naming Test
timeFrame: 1 year
measure: Changes in performance on Modified Wisconsin Card Sorting Test
timeFrame: 1 year
measure: Changes in performance on Grooved Pegboard Test
timeFrame: 1 year
measure: Changes in Composite Cognitive Function Score
timeFrame: 1 year
Other outcomes:
Locations:
city: Baltimore
country: United States
facility: University of Maryland - Administrative Center
state: Maryland
Study officials:
affiliation: University of Maryland, College Park
name: Kimberlly Nordstrom, CCRC
role: STUDY_DIRECTOR
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