Biomarkers for Vascular Contributions to Cognitive Impairment and Dementia Consortium (MarkVCID)

Mass General Brigham

Status: Active, not recruiting

Conditions: Cognitive Impairment; Dementia

Treatments: Other: No interventions

Study type: Observational

Funder types: Other

Identifiers

NCT06284213

5U24NS100591 (U.S. NIH Grant/Contract)

Details and patient eligibility

About

Biomarkers for Vascular Contributions to Cognitive Impairment and Dementia (MarkVCID) is an NIH-funded consortium dedicated to finding biomarkers involved in age-related thinking and memory problems. Alzheimer's disease and other dementias leave signatures on brain scans or in the blood called biomarkers. The MarkVCID study will measure a panel of candidate biomarkers in 1800 participants and watch them closely to see what they tell us about changes in brain function and risk of memory loss.

Age-related problems in thinking and memory represent some of the greatest risks to public health in the US and globally. Diseases that affect small blood vessels in the brain have been shown to be major contributors to these changes. However, research and patient care can be held back by limited biomarkers that identify who should be treated.

The MarkVCID Consortium includes 17 US medical centers, a Coordinating Center, an External Advisory Committee, and NIH leadership. Data and biospecimens collected as part of this research study will be stored in a research database and biorepositories, so that researchers can use this information to study brain function.

Full description

Biomarkers for Vascular Contributions to Cognitive Impairment and Dementia (MarkVCID) is an NIH-funded multisite consortium dedicated to developing promising predictive, diagnostic, target engagement and progression candidate biomarkers of small vessel disease in VCID. MarkVCID is a collaborative consortium of nine North American research sites (consisting of 17 institutions nationwide), a Coordinating Center, External Advisory Committee, and NIH leadership.

MGH serves as the Consortium's Coordinating Center and is comprised of an administrative and data core providing participating research sites with a common support infrastructure that facilitates cross-site collaborations, oversees development of standard operating procedures and data collection methods and manages consortium-wide data.

In phase two of the MarkVCID study, research sites are charged with enrolling and following ≥200 diverse human subjects with cognitive complaints and/or early symptomatic stages of cognitive impairment and dementia potentially associated with cerebrovascular small vessel disease. Sites will share data with the Coordinating Center which will be used for validation studies of chosen consortium biomarkers. Throughout the duration of the study, sites will utilize harmonized procedures and data collection methods to engage in multi-site biomarker validation. Both Cores comply with regulations for the protection of human research subjects (including Good Clinical Practices (GCP), 21 Code of Federal Regulations (CFR)) and with the International Conference on Harmonization (ICH) Regulations E2A and E6.

Enrollment: 1,892 patients

Sex: All

Ages: 60 to 90 years old

Volunteers: Accepts Healthy Volunteers

Inclusion criteria

• Age ≥ 60 and ≤ 90 years

• Diagnosis of normal cognition with at least one criterion for vascular risk*, subjective cognitive decline (preliminary diagnosis based on self-report question or eCog-12), mild cognitive impairment, or mild dementia based on standard research criteria

• Fluent in English or Spanish

• No contraindications to MRI including CVR

• No confounding neurologic, psychiatric, or medical disease

  *Participants with normal cognition must meet at least one criterion (diabetes, OR hypertension plus, OR MRI factors) for vascular risk prior to enrollment:

• Diabetes (at least one of the following):

  • Fasting (8-hour fast, usually overnight) blood sugar ≥126 mg/dL (≥7 mmol/L, or ≥1260 mg/L)
  • Random or Post-prandial blood sugar ≥200 mg/dL (≥11.11 mmol/L, or ≥2000 mg/L)
  • HbA1C ≥6.5% (or ≥47.5412 mmol/mol)
  • Treatment with an anti-diabetic medicine

• Hypertension plus (at least two of the following):

  • Use of anti-hypertensive medications for lowering blood pressure for ≥ 10 years
  • Current use of two or more anti-hypertensive medications for lowering blood pressure
  • One measured blood pressure in a research or clinical setting in the last 2 years with SBP ≥140 or DBP ≥90
  • A second measured blood pressure in a research or clinical setting on a different date in the last 2 years with SBP ≥140 or DBP ≥90
  • Evidence of likely HTN end-organ damage (e.g., LVH, albuminuria, eGFR<60, CHF)

• MRI factors (at least one of the following):

  • Peri-Ventricular Fazekas Extent Grade or Deep Fazekas Extent Grade ≥ 2
  • 1 or more microbleeds
  • 1 or more lacunar infarcts

Exclusion criteria

• Neurologic Disease: Based on the available data and investigator's impression, exclude those with confounding neurologic disease that would interfere with test performance or with biomarker analysis:

  • Frontotemporal lobar degeneration (FTLD)

  • Lewy body dementia (LBD)

  • Parkinson's disease

  • Multi system atrophy

  • Traumatic brain injury (TBI)-related cognitive impairment

  • TBI that interferes with MRI biomarker analyses (e.g., large volume traumatic lesion)

  • Non-small vessel strokes that interfere with test performance (e.g., post-stroke cognitive impairment or aphasia)

  • Non-small vessel strokes that interfere with MRI biomarker analysis (e.g., large volume strokes)

  • CADASIL (Cerebral Autosomal Dominant Arteriopathy with Subcortical Infarcts and Leukoencephalopathy)

  • Individuals known to be receiving, or planning to receive, anti-amyloid immunotherapy*

  • Other neurologic conditions that interfere with test performance or biomarker analysis

    • Individuals prescribed anti-amyloid immunotherapy after MarkVCID enrollment should be kept in the study.

• Medical and Psychiatric Conditions: Exclude those with medical and psychiatric conditions that would confound the course or interfere with test performance:

  • Schizophrenia or other active/severe psychotic disorders

  • Medical or psychiatric conditions likely to interfere with participation or retention (e.g., metastatic or malignant CNS cancer, active/severe depression or anxiety, HIV- Associated Neurocognitive Disorder)

  • Contraindications to MRI procedures, such as:

    • Claustrophobia
    • Cardiac pacemaker
    • Intracranial clips/metal implants

  • Contraindications to CVR:

    • COPD or other respiratory condition requiring oxygen therapy
    • Asthma or other respiratory condition requiring current use of medications such as inhalers

Trial design

1,892 participants in 4 patient groups

Normal Cognition (NC) with at least 1 vascular risk factor

Description:

NC is defined as: 1. No diagnosis of SCD, MCI, or dementia; AND 2. CDR: Sum of Boxes = 0 AND neuropsychological testing in normal range. Participants must have at least 1 of the following criteria prior to enrollment: Diabetes (at least 1): * Fasting (8-hour) blood sugar ≥126 mg/dL * Random or Post-prandial blood sugar ≥200 mg/dL * HbA1C ≥6.5% * Treatment with anti-diabetic medicine Hypertension plus (at least 2): * Use of anti-hypertensive medications for lowering blood pressure for ≥10 years * Current use of 2 or more anti-hypertensive meds for lowering blood pressure * Blood pressure in a research or clinical setting in the last 2 years with SBP ≥140 or DBP ≥90 * Second blood pressure reading in a research or clinical setting in the last 2 years (different date) with SBP ≥140 or DBP ≥90 * Evidence of likely HTN end organ damage MRI factors (at least 1): * Peri-Ventricular Fazekas Extent Grade or Deep Fazekas Extent Grade ≥2 * ≥1 microbleeds * ≥1 lacunar infarcts

Treatment:

Other: No interventions

Subjective Cognitive Decline (SCD)

Description:

Subjective cognitive decline is defined as: 1. Cognitive concerns based on a Short eCog-12 score ≥ 3 (based on administration to participant), AND 2. Normal cognition (neuropsychological testing within normal range).

Treatment:

Other: No interventions

Mild Cognitive Impairment (MCI)

Description:

Mild cognitive impairment is defined as: 1. There is a cognitive concern, i.e., the subject, the co-participant, or a clinician is concerned about a change in cognition compared to the subject's previous level. 2. There is impairment in one or more cognitive domains (memory, language, executive function, attention, and visuospatial skills) that is greater than would be expected for the patient's age and educational background. 3. There is largely preserved independence in functional abilities (no change from prior level of functioning or requires only extra effort and minimal aids or assistance). 4. There is no evidence of dementia (cognitive changes are mild and there is no evidence of a significant impairment in social or occupational functioning).

Treatment:

Other: No interventions

Mild Dementia

Description:

Mild dementia is defined as: 1. The subject has cognitive or behavioral (neuropsychiatric) symptoms that meet all of the following criteria: 1. Interfere with ability to function as before at work or at usual activities? 2. Represent a decline from previous levels of functioning? 3. Are not explained by delirium or major psychiatric disorder? AND 2. Impairment in one\* or more of the following domains. 1. Impaired ability to acquire and remember new information. 2. Impaired reasoning and handling of complex tasks, poor judgment. 3. Impaired visuospatial abilities. 4. Impaired language functions. 5. Changes in personality, behavior, or comportment \* In the event of single-domain impairment (e.g., language in PPA, behavior in bvFTD, posterior cortical atrophy), the subject must not fulfill criteria for MCI. AND 3. CDR: Global Score = 0.5 or 1

Treatment:

Other: No interventions