Clinical trial NCT05785871: Hypertension, Brain Clearance, and Markers of Neurodegeneration
Official title: Hypertension, Brain Clearance, and Markers of Neurodegeneration
Study type: OBSERVATIONAL
Overall status: ACTIVE_NOT_RECRUITING
Conditions: Mild Cognitive Impairment
Hypertension
Lead sponsor: Weill Medical College of Cornell University
Sponsor class: OTHER
Collaborators: name: National Institute of Neurological Disorders and Stroke (NINDS)
First posted: 2023-03-27
Enrollment: 80
Sex: ALL
Minimum age (years): 60
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Cognitively healthy, with and without hypertension, age 60-80, both men and women

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).

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

Primary outcomes:
measure: Change in cerebral blood flow
timeFrame: Baseline and up to 24 month follow up
measure: Change in Brain Clearance
timeFrame: Baseline and up to 24 month follow up
measure: Change in total tau
timeFrame: Baseline and up to 24 month follow up
measure: Change in amyloid 42
timeFrame: Baseline and up to 24 month follow up
measure: Change in cognitive performance
timeFrame: Baseline and up to 24 month follow up
Secondary outcomes:
Other outcomes:
Locations:
city: New York
country: United States
facility: Weill Cornell Medicine
state: New York
Study officials:
affiliation: Weill Cornell MC
name: Lidia Glodzik
role: PRINCIPAL_INVESTIGATOR
References: