Retinal and Cognitive Dysfunction in Type 2 Diabetes

Retinal and Cognitive Dysfunction in Type 2 Diabetes: Unraveling the Common Pathways and Identification of Patients at Risk of Dementia

Sponsors

Lead Sponsor: Hospital Universitari Vall d'Hebron Research Institute

Collaborator: Queen's University, Belfast
Association for Innovation and Biomedical Research on Light and Image
UMC Utrecht
University of Medical Centre Amsterdam
University of Rome Tor Vergata
Ospedale San Raffaele
University of Milan
University of Southern Denmark
Azienda Ospedaliero Universitaria Maggiore della Carita
Hospital Mutua de Terrassa
Institut Catala de Salut
Faculty of Medicine, University of Montenegro
Clinical Center of Montenegro
University of Cadiz
European Infrastructure for Translational Research
Alzheimer Europe
IDF Europe
Anaxomics Biotech
Oxurion
Genesis Biomed

Source Hospital Universitari Vall d'Hebron Research Institute
Brief Summary

The retina shares similar embryologic origin, anatomical features and physiological properties with the brain and hence offers a unique and accessible "window" to study the correlates and consequences of subclinical pathology in patients with cognitive impairment. Our hypothesis is that the neurodegeneration of the retina will run in parallel to the neurodegeneration of the brain and, therefore, the signs of neurodysfunction in the retinal assessment will be more evident in those patients with rapid cognitive decline. Microangiopathy will also participate in cognitive decline and its specific role, as well as usefulness of retinal imaging, will be also examined.

This is a multinational and multicentre cross-sectional study and prospective, longitudinal cohort observational study.

Detailed Description

The study consists of two main parts: a cross-sectional part and a longitudinal part, aimed at a) to determine whether functional and/or structural retinal biomarkers or circulating biomarkers are able to differentiate people with mild cognitive impairment (MCI) within the type 2 diabetes (T2D) population (the investigators will be able to do in the cross-sectional study, and, thus, use retina and/or blood biomarkers as a potential proxy to events taking place in the brain); b)to determine whether functional and/or structural retinal biomarkers or circulating biomarkers can be used to determine the speed of cognitive decline in people with T2D and MCI and those at higher risk of developing dementia.

The cross-sectional study will allow characterization of a large group of individuals with T2D (720 participants) and establish correlations between the various functional and structural retinal endpoints obtained and the presence/absence of mild cognitive impairment (MCI) and dementia. The cross-sectional study will allow identification of T2D patients with MCI; of these a group of 168 T2D patients with MCI and a group of T2D patients without MCI (n=63), which will act as a control group, will be then followed prospectively in the longitudinal cohort study to evaluate end points predictive of cognitive decline and dementia.

The primary objective is: to assess whether retinal sensitivity measured by microperimetry is able to predict cognitive decline and progression to dementia in MCI T2D patients.

The secondary objectives are:

1. To assess whether retinal sensitivity, measured by microperimetry, can identify individuals with MCI among people with T2D.

2. To assess whether eye fixation, measured by microperimetry, can identify individuals with MCI among people with T2D.

3. To assess whether eye fixation measured by microperimetry is able to predict rapid cognitive decline in T2D patients with MCI.

4. To define a T2D phenotype at high risk of developing dementia based on retinal imaging and functional retinal assessments.

5. To determine whether retinal imaging and functional retinal assessments may identify individuals with MCI among people with T2D.

6. To define a T2D phenotype at high risk to develop cognitive decline and dementia based on retinal imaging plus brain imaging.

7. To define a T2D phenotype at high risk to develop dementia based on retinal imaging plus brain imaging plus circulating biomarkers.

8. To establish a score to predict cognitive decline or progression from MCI to dementia based on the variables included in the study.

Overall Status Not yet recruiting
Start Date June 2020
Completion Date December 2023
Primary Completion Date July 2023
Study Type Observational
Primary Outcome
Measure Time Frame
Retinal sensitivity 48 month
Secondary Outcome
Measure Time Frame
Retinal neurodysfunction/ neurodegeneration-1 48 month
Retinal neurodysfunction/ neurodegeneration-2 48 month
Retinal neurodysfunction/ neurodegeneration-3 48 month
Retinal vascular abnormalities-1 48 month
Retinal vascular abnormalities-2 48 month
Brain imaging-1 48 month
Brain imaging-2 48 month
Circulating biomarkers: Hypothesis free analysis 48 month
Geriatric Depression Scale 48 month
Quality of life: EQ-5D-3L 48 month
Visual Functioning Questionnaire 48 month
Diabetes Specific Dementia Risk Score. 48 month
Enrollment 720
Condition
Eligibility

Sampling Method: Non-Probability Sample

Criteria:

Inclusion Criteria:

1. Type 2 diabetes

2. 65 years and older

3. Diabetes duration of at least 5 years

4. Mild to moderate non-proliferative diabetic retinopathy (NPDR), as determined by the evaluating ophthalmologists using fundus examination by slit-lamp biomicroscopy

5. Able to provide informed consent

Prospective study:

In addition to the above, participants enrolled in the prospective longitudinal cohort study should fulfilled the following criteria:

1. Diagnosis of MCI confirmed by a neuropsychological test battery (NTB) and a specialized physician. For the control group the absence of MCI will also be confirmed by a neuropsychological test battery (NTB) and a specialized physician.

2. Diagnosis of mild to moderate NPDR (ETDRS DR level 35 to 47) confirmed by the reading centre.

Exclusion Criteria:

1. Previous history of stroke or neurodegenerative diseases.

2. Severe NPDR, Proliferative DR (PDR), Diabetic Macular Edema (DME) or other eye disorders affecting vision besides these complications of diabetic retinopathy (DR).

3. Previous laser photocoagulation.

4. Other diseases which may induce retinal neurodegeneration (e.g. glaucoma).

5. Subjects with a refractive error ≥ ± 6 D.

6. Media opacities that preclude retinal imaging.

7. HbA1C > 10% (86 mmol/mol).

8. Severe systemic illness or personal circumstances that would not make it possible for patients to fulfil study protocols.

Prospective study:

In addition to the above, participants enrolled in the prospective longitudinal cohort study should fulfilled the following criteria:

1. Established dementia.

Gender: All

Minimum Age: 65 Years

Maximum Age: N/A

Healthy Volunteers: No

Overall Official
Overall Contact

Last Name: Andreea Ciudin, Prof.

Phone: 697817352

Email: [email protected]

Verification Date

February 2020

Responsible Party

Type: Principal Investigator

Investigator Affiliation: Hospital Universitari Vall d'Hebron Research Institute

Investigator Full Name: Andreea Ciudin

Investigator Title: Prof. Dr. Rafael Simo Canonge

Has Expanded Access No
Condition Browse
Arm Group

Label: Cross-sectional cohort

Description: 720 type 2 diabetic patients (>5 years duration), older than 65 years of age

Label: Prospective study-MCI

Description: 168 Patients from the cross-sectional cohort diagnosed with mild cognitive impairment during the cross-sectional evaluation

Label: Prospective study normocognitive

Description: 63 Patients from the cross-sectional cohort without mild cognitive impairment evaluated during the cross-sectional evaluation

Acronym RECOGNISED
Study Design Info

Observational Model: Case-Control

Time Perspective: Prospective

Source: ClinicalTrials.gov