Periodic Reporting for period 1 - RECOGNISED (Retinal and cognitive dysfunction in type 2 diabetes: unraveling the common pathways and identification of patients at risk of dementia)
Período documentado: 2020-01-01 hasta 2021-06-30
There is mounting evidence that type 2 diabetes (T2D) is associated with cognitive impairment and dementia, which can be considered as a “new” long-term diabetic co-morbid complication with dramatic consequences for patients and their families, and a significant impact for healthcare systems. There are no reported phenotypic indicators or reliable tests to identify T2D patients at risk of developing dementia. Since the retina is ontogenically a brain-derived tissue, we propose that the evaluation of retinal parameters related to either neurodegeneration or microvascular disease will be robust and valuable biomarkers to identify those T2D patients at higher risk of developing cognitive impairment and dementia. On this basis the overarching aims of the project are:
1) To investigate the common mechanisms involved in the pathogenesis of DR and cognitive impairment in the T2D.
2) To use the retina as a tool to identifying individuals with T2D at a higher risk of developing cognitive decline or dementia.
The specific objectives of the project are:
1. To identify the molecular links between the brain and the retina in terms of neurodegenerative pathways and neurovascular unit impairment that occurs in experimental models of diabetes and in eyes from human T2D and age-matched donors.
2. To unravel the mechanism of action of common disease-causing mediators in both the brain and the retina.
3. To characterize clinical phenotypes within T2D based on retinal functional and structural characteristics and serum biomarkers in order to stratify the risk and the velocity of cognitive decline.
4. To generate a feasible protocol for the screening of cognitive impairment in the T2D population.
Our multidisciplinary consortium (RECOGNISED) consists of top research leaders in the field belonging to 15 prestigious institutions, as well as EATRIS, IDF-Europe and Alzheimer Europe and 3 SMEs.
1) To investigate the common mechanisms involved in the pathogenesis of DR and cognitive impairment in the T2D.
2) To use the retina as a tool to identifying individuals with T2D at a higher risk of developing cognitive decline or dementia.
The specific objectives of the project are:
1. To identify the molecular links between the brain and the retina in terms of neurodegenerative pathways and neurovascular unit impairment that occurs in experimental models of diabetes and in eyes from human T2D and age-matched donors.
2. To unravel the mechanism of action of common disease-causing mediators in both the brain and the retina.
3. To characterize clinical phenotypes within T2D based on retinal functional and structural characteristics and serum biomarkers in order to stratify the risk and the velocity of cognitive decline.
4. To generate a feasible protocol for the screening of cognitive impairment in the T2D population.
Our multidisciplinary consortium (RECOGNISED) consists of top research leaders in the field belonging to 15 prestigious institutions, as well as EATRIS, IDF-Europe and Alzheimer Europe and 3 SMEs.
The RECOGNISED project has been negatively impacted by the COVID-19 pandemic. The recruitment start in the clinical study was delayed by 4 months and the Coordination team extended the recruitment period by 4.5 months (until 30/09/2021). The slow recruitment rate led to activating the competitive recruitment according to the Consortium Agreement.
The first milestone MS1-Obtaining all ethical approvals, has been achieved on time. The work packages have progressed as follows:
WP1: General coordination and management
Organizational Structures were constituted (Deliverable D1.1). The project was coordinated and managed smoothly. The first amendment to the Grant Agreement was requested and approved by the European Commission during the period.
Three main consortium meetings were held: 1) Kick-off meeting & 1st General Assembly. Barcelona (27.1.2020). 2) 2nd General Assembly. Online (19.6.2020). 3) 3rd General Assembly. Online (21.6.2020).
WP2: Basic research
The final version of the study protocol as submitted to Institutional Animal Care and Use Committees (IACUC) was delivered (D2.1). Collaborations and research activities yielded significant advances that revealed new insights into both brain and retinal pathology in animal models of T2D, AD, and where both phenotypes are combined.
WP3: Cross-sectional and prospective observational clinical studies.
The WP3 team opened all 11 Clinical Sites for recruitment since 09/11/2020 and delivered the documentation required for starting the clinical study (D3.1). A mid-term patients recruitment report has been delivered (D3.2).
WP4: Central Reading and Imaging Processing of the brain and the retina.
The Ophthalmological Reading Centre (AIBILI-CORC) and Brain Imaging Reading Centres (UMCU for MRI and VHIR for PET images) have developed Study-Specific Acquisition Protocols for these ophthalmological and brain examinations (Deliverable D4.1). They have also developed study materials for each CRC analysis and the activities of the centralized analysis of ophthalmological and brain examinations are ongoing. The CORC online platform for exams submission was also made available (Deliverable D4.2).
WP5: Neuropsychological and quality of life assessment.
Harmonization of the neuropsychological test battery for all clinical sites is completed. Several guidelines have been created to assist the clinical sites in data collection to improve data quality (Deliverable D5.1). Results derived from cross-sectional analyses have been reported (Deliverable D5.2).
WP6: Identify circulating biomarkers.
The blood collection is ongoing following the specific SOP (Deliverable D6.1). In addition, we performed a pilot study in order to evaluate the usefulness of serum levels of GFAP and NFL as biomarkers of retinal neurodysfunction progression in a sub-group of patients from the EUROCONDOR cohort (FP7 278040). The results confirm GFAP, a marker of glial activation, in combination with NfL and the other selected biomarkers will enable us to predict both retinal and brain neurodegeneration with a high accuracy.
WP7: Data mining and systems biology.
Base ground activity has been started to retrieve relevant molecular information from existing knowledge.
WP8: Dissemination and exploitation.
WP8 has designed a rigorous translational research strategy plan that includes strategic tasks such as: 1) Identify partners for potential industrial developments; 2) Secure follow-on funding to guarantee the sustainability of the project; and 3) Facilitate rigorous health care technology assessment into (real) clinical setting. The data management plan has been delivered (D8.2).
WP9: Communication Activities.
WP9 partners have developed a first draft of the communications plan, defining the target audiences, identifying key messages and communication channels. VHIR supervised the development of the website (public and private sections). WP9 also created a leaflet and a twitter handle, complemented by the RECOGNISED logo, as well as document/PowerPoint presentation templates that help with the branding of RECOGNISED, and a video presentation of the project (Deliverable D9.2). Alongside these channels, outreach to external stakeholders has also been achieved by leveraging the communication channels of the patient organisation co-leads of WP9, Alzheimer Europe and IDF-Europe. In terms of dissemination and impact, Prof. Rafael Simó (VHIR) was invited to collaborate with the EU-funded PRIME consortium (https://prime-study.eu/) and Noemi Lois (QUB) was invited to present RECOGNISED as a webinar to the members of this consortium.
WP10: Ethics requirements.
Seven deliverables were produced (D10.1-D10.7) demonstrating the ethical compliance of the clinical study.
The first milestone MS1-Obtaining all ethical approvals, has been achieved on time. The work packages have progressed as follows:
WP1: General coordination and management
Organizational Structures were constituted (Deliverable D1.1). The project was coordinated and managed smoothly. The first amendment to the Grant Agreement was requested and approved by the European Commission during the period.
Three main consortium meetings were held: 1) Kick-off meeting & 1st General Assembly. Barcelona (27.1.2020). 2) 2nd General Assembly. Online (19.6.2020). 3) 3rd General Assembly. Online (21.6.2020).
WP2: Basic research
The final version of the study protocol as submitted to Institutional Animal Care and Use Committees (IACUC) was delivered (D2.1). Collaborations and research activities yielded significant advances that revealed new insights into both brain and retinal pathology in animal models of T2D, AD, and where both phenotypes are combined.
WP3: Cross-sectional and prospective observational clinical studies.
The WP3 team opened all 11 Clinical Sites for recruitment since 09/11/2020 and delivered the documentation required for starting the clinical study (D3.1). A mid-term patients recruitment report has been delivered (D3.2).
WP4: Central Reading and Imaging Processing of the brain and the retina.
The Ophthalmological Reading Centre (AIBILI-CORC) and Brain Imaging Reading Centres (UMCU for MRI and VHIR for PET images) have developed Study-Specific Acquisition Protocols for these ophthalmological and brain examinations (Deliverable D4.1). They have also developed study materials for each CRC analysis and the activities of the centralized analysis of ophthalmological and brain examinations are ongoing. The CORC online platform for exams submission was also made available (Deliverable D4.2).
WP5: Neuropsychological and quality of life assessment.
Harmonization of the neuropsychological test battery for all clinical sites is completed. Several guidelines have been created to assist the clinical sites in data collection to improve data quality (Deliverable D5.1). Results derived from cross-sectional analyses have been reported (Deliverable D5.2).
WP6: Identify circulating biomarkers.
The blood collection is ongoing following the specific SOP (Deliverable D6.1). In addition, we performed a pilot study in order to evaluate the usefulness of serum levels of GFAP and NFL as biomarkers of retinal neurodysfunction progression in a sub-group of patients from the EUROCONDOR cohort (FP7 278040). The results confirm GFAP, a marker of glial activation, in combination with NfL and the other selected biomarkers will enable us to predict both retinal and brain neurodegeneration with a high accuracy.
WP7: Data mining and systems biology.
Base ground activity has been started to retrieve relevant molecular information from existing knowledge.
WP8: Dissemination and exploitation.
WP8 has designed a rigorous translational research strategy plan that includes strategic tasks such as: 1) Identify partners for potential industrial developments; 2) Secure follow-on funding to guarantee the sustainability of the project; and 3) Facilitate rigorous health care technology assessment into (real) clinical setting. The data management plan has been delivered (D8.2).
WP9: Communication Activities.
WP9 partners have developed a first draft of the communications plan, defining the target audiences, identifying key messages and communication channels. VHIR supervised the development of the website (public and private sections). WP9 also created a leaflet and a twitter handle, complemented by the RECOGNISED logo, as well as document/PowerPoint presentation templates that help with the branding of RECOGNISED, and a video presentation of the project (Deliverable D9.2). Alongside these channels, outreach to external stakeholders has also been achieved by leveraging the communication channels of the patient organisation co-leads of WP9, Alzheimer Europe and IDF-Europe. In terms of dissemination and impact, Prof. Rafael Simó (VHIR) was invited to collaborate with the EU-funded PRIME consortium (https://prime-study.eu/) and Noemi Lois (QUB) was invited to present RECOGNISED as a webinar to the members of this consortium.
WP10: Ethics requirements.
Seven deliverables were produced (D10.1-D10.7) demonstrating the ethical compliance of the clinical study.
The 48-month project started on 1.1.2020. RECOGNISED applies innovative approaches to identify the molecular mechanisms involved in the high prevalence of cognitive impairment and dementia in T2D population and uses this knowledge to characterize clinical phenotypes (personalized medicine) based on retinal functional and structural characteristics and serum biomarkers in order to stratify the risk and severity of cognitive decline. Previously collected data from registries, cohorts and biobanks appropriately exploited and the generation of robust new data will guide clinical recommendations and open up new therapeutic strategies.
Ultimately, the RECOGNISED project will help to reduce the huge societal and economic burden associated with diabetes-related cognitive impairment.
Ultimately, the RECOGNISED project will help to reduce the huge societal and economic burden associated with diabetes-related cognitive impairment.