Hypertension, Brain Clearance, and Markers of Neurodegeneration

NCT05785871 | Completed

• 2 other identifiers: 19-050200735R01NS104364-03
• Study Type: observational
• Target: 80
• Locations: 1 country
• Sites: 1

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.

Conditions

Mild Cognitive Impairment; Hypertension

Outcome Measures

Primary Outcomes (5)

• Change in cerebral blood flow

  cerebral blood flow with arterial spin labeling MRI

  Baseline and up to 24 month follow up

• Change in Brain Clearance

  the rate of radiotracer removal from the brain ventricle after injection of MK-6240 images, measured with positron emission tomography

  Baseline and up to 24 month follow up

• Change in total tau

  total tau protein measured in cerebrospinal fluid

  Baseline and up to 24 month follow up

• Change in amyloid 42

  amyloid 42 protein measured in cerebrospinal fluid

  Baseline and up to 24 month follow up

• Change in cognitive performance

  A composite score of tests assessing: Immediate and delayed memory (score ranges in parentheses): Craft Story immediate (0-44) and delayed recall (0-44), Guild battery immediate (0-21) and delayed recall (0-21) of paragraph and word pairs immediate (0-10) and delayed (0-10). Working memory: Number Span test forward (0-14) and backward (0-14) Naming: Verbal Naming Test (0-26). Attention: Trail Making Test part A (0-25) Executive functions: Trail Making Test Part B (score range 0-13) and Wisconsin Sorting Card Test (0-128). Verbal Fluency: Category Fluency: animals (0-30) and vegetables (0-30), category letters F (0-30) and L (0-30). Each test is transformed into normative z-score. For each domain the scores are expressed as a composite z-score of all the tests assessing a given domain. The score range from -3.0 - to +3.0 higher indicating better performance.

  Baseline and up to 24 month follow up

Study Arms (3)

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).

Normotensive

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

Controlled Hypertension

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

Eligibility Criteria

• Age: 60 Years - 80 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Cognitively healthy, with and without hypertension, age 60-80, both men and women

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Weill Medical College of Cornell University: lead
• National Institute of Neurological Disorders and Stroke (NINDS): collaborator

Study Sites (1)

Weill Cornell Medicine

New York, New York, 10065, United States

Location

Biospecimen

Retention: SAMPLES WITH DNA

In addition to the tests and goals described, participants' data, images, blood samples, cerebrospinal fluid and extracted DNA (Deoxyribonucleic acid) may, with the subject's permission, also be stored and used for current and future research purposes not outlined here. Blood samples are stored including whole blood, serum, plasma, red blood cells (erythrocytes) and white blood cells (leukocytes). Data stored will encompass all clinical, cognitive and imaging data.

MeSH Terms

Conditions

Cognitive Dysfunction; Hypertension

Condition Hierarchy (Ancestors)

Cognition Disorders; Neurocognitive Disorders; Mental Disorders; Vascular Diseases; Cardiovascular Diseases

Study Officials

• Lidia Glodzik

  Weill Cornell MC

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Target Duration: 2 Years
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 14, 2023
• First Posted: March 27, 2023
• Study Start: November 18, 2020
• Primary Completion: June 30, 2025
• Study Completion: June 30, 2025
• Last Updated: August 27, 2025

Record last verified: 2025-08

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL
• Time Frame: 5 years
• Access Criteria: Researchers who provide IRB-approved, methodologically sound proposal.

Locations

US (1)