Clinical Applicability of pCASL as a Substitute for FDG-PET in MCI and SCD Patients (CAPE)

Clinical Applicability of Pseudo-continuous Arterial Spin Labeling as a Substitute for FDG-position Emission Tomography in MCI and SCD Patients

The goal of this observational study is to compare cerebral perfusion patterns with pseudo-continuous arterial spin labeling (pCASL) and brain metabolism patterns with fluorodeoxyglucose-position emission tomography (FDG-PET) in patients with mild cognitive impairment (MCI) and subjective cognitive decline (SCD). The main questions it aims to answer are:

• Do pCASL sequences identify hypoperfusion patterns that correlate well with FDG-PET hypometabolic patterns?
• Are there differences in this correlation in terms of cerebrospinal fluid (CSF) profiles?
• Can hypoperfusion patterns in pCASL predict conversion to dementia? Participants will undergo brain 3 Tesla magnetic resonance imaging (MRI), FDG-PET, lumbal puncture and blood collection to analyze amyloid beta and tau, yearly detailed neuropsychological tests for three years.

Study Overview

• Status: Recruiting
• Conditions: Mild Cognitive Impairment; Subjective Cognitive Decline
• Intervention / Treatment: Diagnostic test: pCASL

• Study Type: Observational
• Enrollment (Estimated): 150

Contacts and Locations

• Study Contact: Name: Carlo Ferrarese, MD, PhD; Phone Number: +390392333595; Email: carlo.ferrarese@unimib.it

Study Locations

• Italy
  • MB
    • Monza, MB, Italy, 20900
      • Recruiting
      • Fondazione IRCCS San Gerardo dei Tintori
      • Contact: Carlo Ferrarese, MD, PhD; Phone Number: +390392333595; Email: carlo.ferrarese@unimib.it
      • Principal Investigator: Gianpaolo Basso, MD, PhD
      • Principal Investigator: Carlo Ferrarese, MD, PhD
      • Sub-Investigator: Federico Emanuele Pozzi, MD
      • Sub-Investigator: Fulvio Da Re, MD, PhD
      • Sub-Investigator: Valeria Isella, MD, PhD
      • Sub-Investigator: Cinzia Crivellaro, MD
      • Sub-Investigator: Lucio Tremolizzo, MD, PhD, PGDip
      • Sub-Investigator: Valeria Cerina, MSc
      • Sub-Investigator: Ildebrando Appollonio, MD, PhD
      • Sub-Investigator: Elisa Conti, PhD
      • Sub-Investigator: Elisabetta De Bernardi, PhD
      • Sub-Investigator: Sabrina Morzenti, PhD
      • Sub-Investigator: Lorenzo Jonghi Lavarini, MD
      • Sub-Investigator: Monica Musarra, MD
      • Sub-Investigator: Jacopo Cosimo Di Francesco, MD, PhD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

Patients with mild cognitive impairment

Description

Inclusion Criteria:

• Patients with mild cognitive impairment or subjective cognitive decline according to established criteria
• Clinical Dementia Rating scale of 0 or 0.5
• Signed informed consent before study entry

Exclusion Criteria:

• Contraindication to brain MRI, FDG-PET or lumbar puncture
• Secondary causes of cognitive decline
• Known major neurological or psychiatric comorbidities
• History of substance or alcohol abuse
• Known causes of cerebral brain perfusion alterations
• Enrollment in anti-amyloid or anti-tau drugs trials

Study Plan

How is the study designed?

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Correlation between brain hypoperfusion and brain hypometabolism at baseline	The investigators will correlate cerebral perfusion indices and standardized uptake value ratios (SUVr) ratios for each pre-specified region of interest (ROI) within statistical parametric mapping (SPM) Automatic Anatomic Labeling (AAL), after coregistration on T1 sequences	Baseline
Correlation between brain hypoperfusion and brain hypometabolism at baseline according to CSF profile	The investigators will correlate cerebral perfusion indices and SUVr for each pre-specified ROI (region of interest) within SPM Automatic Anatomic Labeling (AAL), after coregistration on T1 sequences. This analysis will be done within subgroups according to CSF status according to amyloid beta, phosphorylated tau and total tau.	Baseline

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Differences among brain hypoperfusion patterns according to amyloid and tau status	The investigators will analyze differences in brain perfusion indices for each ROI among patients wit amyloid positive status, amyloid and tau negative status, and amyloid negative - tau positive status	Baseline
Correlations between brain hypoperfusion and neuropsychological tests	The investigators will perform correlations between brain hypoperfusion indices for each ROI and various neuropsychological (NPS) test scores	Baseline, 1 year, 2 years
Predictive properties of brain hypoperfusion and brain hypometabolism for conversion to dementia	The investigators will analyze correlations between each ROI hypoperfusion and conversion to dementia rates within the prespecified time frame. In case of significant associations, a receiver operating characteristic curve (ROC) analysis will be carried out to individuate optimal cut-offs for cerebral blood flow indices and SUVr to predict conversion of dementia	1 year, 2 years
Correlations between brain hypoperfusion and CSF and blood biomarkers	The investigators will perform correlations between brain hypoperfusion indices for each ROI and values of CSF and blood amyloid beta, phosphorylated tau and total tau	Baseline

Collaborators and Investigators

• Sponsor: University of Milano Bicocca

Study record dates

Study Major Dates

• Study Start (Actual): June 3, 2022
• Primary Completion (Estimated): June 1, 2024
• Study Completion (Estimated): June 1, 2026

Study Registration Dates

• First Submitted: February 22, 2023
• First Submitted That Met QC Criteria: February 22, 2023
• First Posted (Actual): March 6, 2023

Study Record Updates

• Last Update Posted (Actual): August 1, 2023
• Last Update Submitted That Met QC Criteria: July 27, 2023
• Last Verified: July 1, 2023

More Information

Terms related to this study

• Keywords: biomarkers; mild cognitive impairment; subjective cognitive decline; pseudo-continuous arterial spin labeling; fluorodeoxyglucose positron emission tomography
• Additional Relevant MeSH Terms: Mental Disorders; Neurocognitive Disorders; Cognition Disorders; Cognitive Dysfunction
• Other Study ID Numbers: CAPE

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No