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

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

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

Conditions
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Mild Cognitive Impairment, Alzheimer Disease, Dementia

Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 50 Years
Maximum Age: 90 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Patient Participants<br>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<br>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?
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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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Neurodegenerative Diseases, Diagnosis, Prognosis, Diagnostic Imaging, Neuroimaging, Magnetic Resonance Imaging, Diffusion Tensor Imaging