Vascular Aspects in Dementia: Part 2

NCT06322121 | Active Not Recruiting

• 1 other identifier: NL83653.058.23
• Study Type: observational
• Target: 120
• Locations: 1 country
• Sites: 1

Brief Summary

Cerebral amyloid angiopathy (CAA), a common cerebrovascular small vessel disease (SVD), is a frequently (98%) found co-morbidity at autopsy in patients with Alzheimer's disease (AD). Current in vivo hallmarks of CAA represent changes relatively late in the disease process and leaves CAA in AD often undetected. Recently, it was shown that decreased vascular reactivity (VR) measured with blood oxygen level dependent (BOLD) MRI, after visual stimulus, is an early CAA marker. With BOLD-MRI to detect decreased VR in different stages of AD, it was shown that increasing stages of AD associate with decreasing VR independent of age, classic SVD markers and atrophy. Moreover, VR is associated with cognitive deficits. Therefore, cross-sectional data indicate that decreased VR is an important co-morbidity already in early stages of AD with an independent effect on disease severity. In this respect, the study aim is to determine the natural course of the decrease of VR in both controls and (early stage) AD patients to monitor AD disease progression. This is an essential step to aid in the development and application of effective treatment as it is expected that CAA can cause/worsen AD pathology.

Conditions

Dementia

Outcome Measures

Primary Outcomes (3)

• Vascular reactivity - BOLD amplitude

  The change in BOLD signal in response to visual stimulation as measured by the amplitude of the BOLD response in percentage signal change between stimulus on and off.

  1,5 - 2 years between time point 1 and time point 2

• Vascular reactivity - time-to-peak

  The time-to-peak response (sec) is defined as the duration from the beginning of visual stimulation to the peak response.

  1,5 - 2 years between time point 1 and time point 2

• Vascular reactivity - time-to-baseline

  The time-to-baseline response (sec) is defined as the duration from the end of the stimulus to baseline.

  1,5 - 2 years between time point 1 and time point 2

Secondary Outcomes (9)

• Intracranial hemorrhage

  1,5 - 2 years between time point 1 and time point 2

• Lobar microbleeds

  1,5 - 2 years between time point 1 and time point 2

• Subarachnoidal hemorrhage

  1,5 - 2 years between time point 1 and time point 2

• Superficial siderosis

  1,5 - 2 years between time point 1 and time point 2

• Lacunes

  1,5 - 2 years between time point 1 and time point 2

Study Arms (4)

Dementia patients

Patients with a dementia diagnosis; probable Alzheimer or mixed-type dementia

Other: MRI

MCI patients

Patients with a MCI diagnosis; patients demonstrating cognitive deficits on neuropsychological testing but not fulfilling the criteria for dementia.

Other: MRI

SCI patients

Patients not demonstrating cognitive deficits on neuropsychological testing are classified as SCI

Other: MRI

Controls

Control subject without cognitive complaints

Other: MRI

Interventions

MRI OTHER

Assessment of vascular reactivity and CAA/SVD MRI markers

Controls; Dementia patients; MCI patients; SCI patients

Eligibility Criteria

• Age: 50 Years - 90 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Patients who attended a memory clinic and healthy controls

You may qualify if:

• Participants who were included in our previous CASCADE study (P19.039).
• Capable of giving informed consent (see appendix)
• Patients who attended a memory clinic within one year ago
• Diagnosed with (mixed) probable AD
• Diagnosed as MCI
• Diagnosed as SCI
• Age between 50-90 years
• Capable of giving informed consent (see appendix)
• Control subjects
• Healthy adults without memory complaints
• Age between 50 -90 years
• Capable of giving informed consent

You may not qualify if:

• Contra-indication to MRI scanning:
• Claustrophobia
• Pacemakers and defibrillators
• Nerve stimulators
• Intracranial clips
• Intraorbital or intraocular metallic fragments
• Cochlear implants
• Ferromagnetic implants
• Hydrocephaluspump
• Intra-utrine device (not all types) Permanent make-up
• Tattoos above the shoulders (not all)
• Specific contraindications to fMRI
• Seizure within prior year.
• Noncorrectable visual impairment.
• MMSE \< 19 points (measured at moment of screening or at memory clinic with a maximum of 6 months in retrospect)

Sponsors & Collaborators

• Leiden University Medical Center: lead

Study Sites (1)

Leids Universitair Medisch Centrum

Leiden, 2333 ZA, Netherlands

Location

Biospecimen

Retention: SAMPLES WITH DNA

2 ml saliva for APOE genotype

MeSH Terms

Conditions

Dementia

Condition Hierarchy (Ancestors)

Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Neurocognitive Disorders; Mental Disorders

Study Design

• Study Type: observational
• Observational Model: CASE CONTROL
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: dr. Principal Investigator

Study Record Dates

• First Submitted: December 11, 2023
• First Posted: March 20, 2024
• Study Start: September 4, 2023
• Primary Completion (Estimated): September 1, 2026
• Study Completion (Estimated): September 1, 2026
• Last Updated: September 15, 2025

Record last verified: 2025-09

Locations

NL (1)