Hypertension, Brain Clearance, and Markers of Neurodegeneration

NCT ID: NCT05785871

Last Updated: 2025-08-27

Basic Information

• Recruitment Status: COMPLETED
• Total Enrollment: 80 participants
• Study Classification: OBSERVATIONAL
• Study Start Date: 2020-11-18
• Study Completion Date: 2025-06-30

Brief Summary

The purpose of this research study is to measure cerebrospinal fluid (CSF) clearance in subjects with and without high blood pressure. CSF cushions the brain from impact and carries waste products from the brain to the bloodstream. This process is known as clearance. Impaired removal of proteins from the aging brain causes their buildup and may contribute to an increased risk for Alzheimer's disease. It is also suspected that clearance may be related to the health of vessels carrying the blood throughout the brain. It is known that high blood pressure damages blood vessels and thus may impair clearance. In this project we will examine if having high blood pressure is related to impaired brain clearance and whether treating high blood pressure improves clearance and reduces buildup of Alzheimer's disease-related proteins.

Participants will be asked to undergo a medical examination, testing of memory, brain imaging (both magnetic resonance and positron emission tomography, and spinal tap at the beginning of the study and 1 -2 years later.

Detailed Description

Over 5 years the investigator will conduct a 24-month longitudinal study of 80 cognitively healthy subjects 60-80 years old, classified at baseline into the following groups: 1) Normotensive NT (n=20), 2) Controlled hypertension C-HTN (n=20), 3) Uncontrolled hypertension or Untreated hypertension UU-HTN (n=30).

For subjects in the NT and C-HTN groups this will be an observational longitudinal study with clinical, imaging and CSF (cerebrospinal fluid) assessment at baseline and 24 month follow-up, with 3 visits to monitor BP (blood pressure) in-between (both at the office and using home BP monitoring). Subjects in the UU-HTN group after having completed their baseline evaluation will be referred for a further evaluation of HTN (hypertension) and an intervention. Intervention: the initiation of treatment or treatment modification to achieve the SBP (systolic blood pressure) goal of <140 mmHg. Subjects will be referred to their physician or, in case they do not have one, to the study cardiologist for treatment according to current guidelines. Imaging at 0 and 24 month consist of MRI (magnetic resonance imaging) with ASL (arterial spin labeling) and brain clearance imaging using 18F-MK6240 PET (positron emission tomography). CSF assessment includes Aβ42 (amyloid beta 42), t-tau (total tau) and p-tau181 (tau phosphorylated at threonine 181).

Conditions

Mild Cognitive Impairment; Hypertension

Study Design

• Observational Model Type: COHORT
• Study Time Perspective: PROSPECTIVE

Study Groups

Untreated Hypertension

in office SBP ≥140 at two separate occasions and currently treated with antihypertensive medications (uncontrolled), or in office SBP ≥ 140 at two different occasions and no current treatment (untreated).

No interventions assigned to this group

Normotensive

in office SBP\<140 mmHg, no treatment with antihypertensive medications

No interventions assigned to this group

Controlled Hypertension

in office SBP \<140 and current treatment with antihypertensive medications

No interventions assigned to this group

Eligibility Criteria

Inclusion Criteria

• Male and female subjects between 60-80 years old
• All subjects will speak English as their first language or demonstrate proficiency in English.
• All subjects will have normal cognition at baseline: a Clinical dementia rating CDR=0, Global deterioration Scale GDS <2
• For the HTN subjects: systolic HTN defined according to Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood pressure (JNC) 7 report. Specifically: Blood pressure in the ranges greater or equal to 140 mmHG, which is a mean of three seated BP readings on each of two or more office visits

Exclusion Criteria

• Non-essential hypertension
• Diabetes
• Isolated diastolic hypertension
• Neurodegenerative disorders (i.e Parkinson disease)
• Dementia or Mild cognitive impairment at baseline
• Long life major depression. Baseline scores greater or equal to 20 on Beck Depression Inventory at baseline
• Long-life DSM-IV axis 1 disorders
• Mental retardation
• Substance abuse

• Minimum Eligible Age: 60 Years
• Maximum Eligible Age: 80 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

National Institute of Neurological Disorders and Stroke (NINDS)

NIH

Sponsor Role: collaborator

Weill Medical College of Cornell University

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Lidia Glodzik

Role: PRINCIPAL_INVESTIGATOR

Weill Cornell MC

Locations

Weill Cornell Medicine

New York, New York, United States

Countries

United States

Other Identifiers

5R01NS104364-03

Identifier Type: NIH

Identifier Source: secondary_id

View Link

19-05020073

Identifier Type: -

Identifier Source: org_study_id