Cortical Disarray Measurement in Mild Cognitive Impairment and Alzheimer's Disease (CONGA)

An Observational Longitudinal Cohort Study to Investigate Cortical Disarray Measurement in Mild Cognitive Impairment and Alzheimer's Disease

The aim of this study is to find out whether a new image analysis technique called Cortical Disarray Measurement (CDM) could be used to help better diagnose Alzheimer's disease. This study will see whether changes on CDM can be used to identify Alzheimer's disease from a group of people living with memory and thinking problems. The study will also explore how CDM relates to changes in memory or thinking over time.

Study Overview

• Status: Active, not recruiting
• Conditions: Dementia; Alzheimer Disease; Mild Cognitive Impairment

Detailed Description

This is a multi-centre observational longitudinal cohort study to evaluate and optimise the Cortical Disarray Measurement (CDM) technique for diagnosis and prognosis in patients with mild cognitive impairment and prodromal / mild Alzheimer's Disease. CDM is a novel MRI analysis tool that quantifies cortical and regional diffusion tensor imaging signals in grey matter to observe pathological changes related to neurodegeneration. Participants in this study will be monitored for 2 years.

Research Aims:

• Assess the accuracy of CDM in detecting progressive change in cognitive and functional measures over 2 years in participants presenting with mild cognitive impairment or early dementia.
• Determine the relationship between CDM (both cross-sectionally and longitudinally) and change on standard cognitive and functional assessment measures.
• Explore patient and companion views and experiences of the diagnostic journey for dementia and their views on CDM implementation.
• To explore the costs and consequences of introducing CDM-augmented MRI as a form of early diagnosis of Alzheimer's disease in people presenting with MCI or mild AD compared to current practice.

• Study Type: Observational
• Enrollment (Estimated): 400

Contacts and Locations

Study Locations

• United Kingdom
  • Bournemouth, United Kingdom
    • Dorset Healthcare University NHS Foundation Trust
  • Cardiff, United Kingdom
    • Cardiff And Vale University Health Board
  • Hampshire
    • Southampton, Hampshire, United Kingdom, SO16 6YD
      • University Hospital Southampton NHS Foundation Trust

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 46 years to 86 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

A total of 200 patient participants and 200 study companions will be recruited to the study. Patient participants will have a diagnosis of mild cognitive impairment or prodromal / mild Alzheimer's Disease. Participants with a global CDR score of 0.5 and 1 will be recruited in a minimum of a 2:1 ratio respectively in the study.

Description

PATIENT PARTICIPANTS

Inclusion Criteria:

• Diagnosis of mild cognitive impairment (MCI) or prodromal Alzheimer's Disease (AD) as defined by National Institute on Ageing/Alzheimer's Association (NIA/AA) diagnostic criteria for MCI/prodromal AD, NOT including MCI unlikely due to AD; OR, Diagnosis of Alzheimer's disease as defined by NIA/AA criteria for probable AD
• Clinical dementia rating (CDR) scale global score of very mild or mild (0.5 or 1) impairment
• Ability to undergo and tolerate MRI scans, with no contraindications to MRI
• Ability to tolerate blood draws
• Ability to give informed consent to participate in the study

Exclusion Criteria:

• Do not meet the inclusion criteria
• No study companion available
• Individuals with a non-progressive learning disability
• Pregnant or intending to become pregnant during the study

COMPANION PARTICIPANTS

Inclusion Criteria:

• Aged over 18 years
• Sufficient knowledge on study participant's condition to complete companion assessments of the patient, in the investigator's judgement
• Able and willing to attend all clinical visits for completion of companion assessments or provide the relevant assessments remotely via phone or video call

Exclusion Criteria:

• A condition or reason, in the investigator's judgement, that would question the validity of the acquired companion reported data
• Individuals who are not fluent in English

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Prospective

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort
Patient Participants; Patient participants will have a diagnosis of mild cognitive impairment or prodromal / mild Alzheimer's Disease. Participants with a global CDR score of 0.5 and 1 will be recruited in a minimum of a 2:1 ratio respectively in the study.
Study Companions; Study companions will have sufficient knowledge on the patient participant's condition to complete companion assessments of the patient, in the investigator's judgement, for example they may be carers of the patients.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
CDR Progression	CDR Progression defined as a binary variable (yes/no) indicating either an increase in global outcome on Clinical Dementia Rating (CDR) scale (which takes value 0, 0.5, 1, 2 or 3, with higher scores reflecting more severe dementia), or an increase greater than, or equal to, 2 points on CDR Sum of Boxes (which takes values from 0 to 18 with higher values indicating a worse outcome)	Baseline (Study day 1) to month 24

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
CDR Sum of Boxes	Change from baseline in the Clinical Dementia Rating (CDR) Sum of Boxes. CDR Sum of boxes is the sum over 6 domains (memory, orientation, judgment & problem solving, community affairs, home & hobbies, and personal care), each rated on a 5-point scale (0, 0.5, 1, 2, 3), giving a total score that ranges from 0 to 18, with higher values indicating a worse outcome.	Baseline (Study day 1) to month 24
ADAS-cog	Change from baseline in Alzheimer's Disease Assessment Scale - Cognitive subscale (ADAS-cog). Higher scores for ADAS-Cog represent a worse outcome.	Baseline (Study day 1) to month 24
MMSE	Change from baseline in Mini Mental State Examination (MMSE). MMSE ranges from 0 to 30, with lower scores representing a worse outcome.	Baseline (Study day 1) to month 24
ADCOMS	Change from baseline in Alzheimer's disease composite score (ADCOMS). The range of ADCOMS is between 0 and 1.97, with higher scores representing a worse outcome.	Baseline (Study day 1) to month 24
RBANS	Change from baseline in the RBANS total score. The repeatable battery for the assessment of neuropsychological status (RBANS) is a brief neuropsychological battery. The total score can classify patients as follows: Average/Mild Impairment (standard scores of 70 or above), Moderate Impairment (standard scores from 55 to 69), and Severe Impairment (standard scores <54), such that lower scores indicate a worse outcome.	Baseline (Study day 1) to month 24
ADCS-ADL	Change from baseline in Alzheimer's Disease Cooperative Study Activities of Daily Living Scale (ADCS-ADL). ADCS-ADL	Baseline (Study day 1) to month 24
Functional Activities Questionnaire (FAQ)	The Functional Activities Questionnaire (FAQ) measures instrumental activities of daily living. Scores range from 0 (independent) to 30 (dependent), with higher scores indicating a worse outcome.	Baseline (Study day 1) to month 24
Institutionalisation or POC	Institutionalisation in care home or nursing home or implementation of package of care (POC) for dementia. Binary outcome (yes, no), with "yes" indicating a worse outcome.	Baseline (Study day 1) to month 24
Death (any cause)	Death due to any cause	Baseline (Study day 1) to month 24
EQ-5D-5L (Patient Participant)	EuroQuol EQ-5D-5L is an instrument to describe and value health on five dimensions: mobility, self-care, usual activities, pain/discomfort and anxiety/depression. Each dimension has 5 levels: no problems, slight problems, moderate problems, severe problems and extreme problems.	Baseline (Study day 1) to month 24
EQ-5D-5L (Study Companion)	EuroQuol EQ-5D-5L is an instrument to describe and value health on five dimensions: mobility, self-care, usual activities, pain/discomfort and anxiety/depression. Each dimension has 5 levels: no problems, slight problems, moderate problems, severe problems and extreme problems.	Baseline (Study day 1) to month 24
Zarit Burden Interview	The Zarit Burden Interview (ZBI) assesses caregiver perceptions of burden. Higher scores indicate a worse outcome.	Baseline (Study day 1) to month 24
Health and social care resource usage	Health and social care resource usage questionnaire. Higher values indicate a worse outcome.	Baseline (Study day 1) to month 24

Collaborators and Investigators

• Sponsor: University Hospital Southampton NHS Foundation Trust
• Collaborators: Cardiff University; University of Oxford; University of Southampton; Cardiff and Vale University Health Board; Bournemouth University; Oxford Brain Diagnostics Ltd
• Investigators: Principal Investigator: Christopher Kipps, PhD, University Hospital Southampton NHS Foundation Trust; Study Chair: Steven Chance, PhD, Oxford Brain Diagnostics Ltd

Study record dates

Study Major Dates

• Study Start (Actual): September 28, 2022
• Primary Completion (Estimated): September 1, 2026
• Study Completion (Estimated): September 1, 2026

Study Registration Dates

• First Submitted: September 16, 2022
• First Submitted That Met QC Criteria: October 11, 2022
• First Posted (Actual): October 13, 2022

Study Record Updates

• Last Update Posted (Actual): May 7, 2026
• Last Update Submitted That Met QC Criteria: May 1, 2026
• Last Verified: April 1, 2026

More Information

Terms related to this study

• Keywords: Prognosis; Magnetic Resonance Imaging; Diagnosis; Diffusion Tensor Imaging; Neuroimaging; Neurodegenerative Diseases; Diagnostic Imaging
• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Mental Disorders; Pathologic Processes; Neurocognitive Disorders; Cognition Disorders; Tauopathies; Pathological Conditions, Signs and Symptoms; Cognitive Dysfunction; Alzheimer Disease; Disease; Dementia; Neurodegenerative Diseases
• Other Study ID Numbers: RHM NEU0402; NIHR202146 (Other Grant/Funding Number: National Institute for Health Research)

Drug and device information, study documents

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