Periodic Reporting for period 4 - RECOGNISED (Retinal and cognitive dysfunction in type 2 diabetes: unraveling the common pathways and identification of patients at risk of dementia)
Período documentado: 2024-07-01 hasta 2024-12-31
There is growing evidence that type 2 diabetes (T2D) is associated with cognitive impairment and dementia, which can be considered a long-term diabetic co-morbid complication with dramatic consequences for patients and their families, and a significant impact on 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.
With the prevalence of T2D and dementia rising in ageing populations, this intersection represents a major societal challenge. Early identification of individuals at risk of cognitive decline can significantly reduce personal, familial, and healthcare system burdens. By identifying retinal markers that correlate with brain changes, RECOGNISED aims to establish a low-cost, non-invasive screening tool for the early detection of dementia risk in the T2D population. This aligns with public health priorities around dementia prevention, improved chronic disease management, and health system sustainability.
The project had two overarching aims: 1) To investigate the common mechanisms involved in the pathogenesis of DR and cognitive impairment in T2D. 2) To use the retina to identify individuals with T2D at a higher risk of developing cognitive decline or dementia.
Specific objectives included identifying the molecular links between brain and retinal degeneration, clarifying the mechanisms of shared disease mediators, characterising clinical phenotypes within T2D based on imaging and biomarkers, and developing a feasible cognitive screening protocol for this population.
The RECOGNISED consortium brought together leading experts from 15 institutions, three SMEs, and key patient and clinical advocacy organisations such as EATRIS, IDF-Europe, and Alzheimer Europe.
Conclusions of the action - Despite delays due to the COVID-19 pandemic, recruitment for the clinical cohort was completed, and a range of preclinical and clinical data has been generated and partially analyzed. Nine open-access publications have emerged from the project. The research identified molecular links—such as tau protein phosphorylation and neuroinflammatory pathways—shared between the retina and brain in diabetes and Alzheimer’s models. Preliminary evidence supports the retina and in particular the parameters assessed by microperimetry (retinal sensitivity and gaze fixation) and portable electroretinography (RETeval) as promising tools for early identification of dementia risk. While full data analysis is still underway, RECOGNISED has laid a strong foundation for future research and clinical translation aimed at mitigating the dual burden of T2D and dementia.
With the prevalence of T2D and dementia rising in ageing populations, this intersection represents a major societal challenge. Early identification of individuals at risk of cognitive decline can significantly reduce personal, familial, and healthcare system burdens. By identifying retinal markers that correlate with brain changes, RECOGNISED aims to establish a low-cost, non-invasive screening tool for the early detection of dementia risk in the T2D population. This aligns with public health priorities around dementia prevention, improved chronic disease management, and health system sustainability.
The project had two overarching aims: 1) To investigate the common mechanisms involved in the pathogenesis of DR and cognitive impairment in T2D. 2) To use the retina to identify individuals with T2D at a higher risk of developing cognitive decline or dementia.
Specific objectives included identifying the molecular links between brain and retinal degeneration, clarifying the mechanisms of shared disease mediators, characterising clinical phenotypes within T2D based on imaging and biomarkers, and developing a feasible cognitive screening protocol for this population.
The RECOGNISED consortium brought together leading experts from 15 institutions, three SMEs, and key patient and clinical advocacy organisations such as EATRIS, IDF-Europe, and Alzheimer Europe.
Conclusions of the action - Despite delays due to the COVID-19 pandemic, recruitment for the clinical cohort was completed, and a range of preclinical and clinical data has been generated and partially analyzed. Nine open-access publications have emerged from the project. The research identified molecular links—such as tau protein phosphorylation and neuroinflammatory pathways—shared between the retina and brain in diabetes and Alzheimer’s models. Preliminary evidence supports the retina and in particular the parameters assessed by microperimetry (retinal sensitivity and gaze fixation) and portable electroretinography (RETeval) as promising tools for early identification of dementia risk. While full data analysis is still underway, RECOGNISED has laid a strong foundation for future research and clinical translation aimed at mitigating the dual burden of T2D and dementia.
Through integrated clinical research, biological analysis, and advanced imaging, the project has delivered major results in patient studies, biomarker identification, cognitive assessment, and data integration.
1. The clinical study achieved full patient recruitment across multiple centres, enabling the collection of critical longitudinal data despite initial delays due to the pandemic. This dataset forms the basis for current and future analyses on disease progression and dementia risk.
2. Preclinical research confirmed that T2D accelerates neurodegenerative processes similar to those observed in Alzheimer’s disease. Animal models revealed shared molecular signatures (i.e. pTau-217) between the brain and retina, including tau hyperphosphorylation and protein misfolding. These discoveries highlight new therapeutic targets and reinforce the connection between diabetic retinal changes and brain degeneration.
3. Preliminary results show that the assessment of retinal neurodysfunction by using microperimetry and portable ERG (RETeval) can predict cognitive decline in patients with T2D. The combination of a clinical score (DSDRS) + pupillary reactivity assessed by RETeval seems a feasible and cost-efficient examination for the screening of cognitive impairment in people with T2D over 65 years.
4. Cognitive testing was conducted using a validated neuropsychological battery tailored for the T2D population. We have found that visuo-construction is the first domain impaired in the T2D population over 65 years. In parallel, circulating blood biomarkers were investigated as non-invasive indicators of cognitive decline. Several biomarkers (i.e. pTau-217, pTau-231) have been identified in both cross-sectional and prospective studies.
5. Advanced imaging, including MRI and retinal scans, was used to assess structural and functional alterations. The 7T MRI sub-study unravelled promising candidate biomarkers. Further analysis aims to integrate clinical, imaging, and molecular data.
6. Using systems biology, the project integrated clinical, biological, and imaging data to understand disease mechanisms and develop predictive models for dementia in T2D. Although two final deliverables (D5.3 and D7.3) were delayed due to COVID-related constraints, their analyses continue beyond the project’s official close.
7. Exploitation and Dissemination: Fifteen deliverables were submitted during the final period, alongside nine open-access publications. A Business Plan, Innovation Management Plan, and Dissemination Plan were produced. The consortium actively engaged in scientific events, public communication, and social media outreach. A catalogue of exploitable results was also developed to guide future collaborations and potential commercial applications.
1. The clinical study achieved full patient recruitment across multiple centres, enabling the collection of critical longitudinal data despite initial delays due to the pandemic. This dataset forms the basis for current and future analyses on disease progression and dementia risk.
2. Preclinical research confirmed that T2D accelerates neurodegenerative processes similar to those observed in Alzheimer’s disease. Animal models revealed shared molecular signatures (i.e. pTau-217) between the brain and retina, including tau hyperphosphorylation and protein misfolding. These discoveries highlight new therapeutic targets and reinforce the connection between diabetic retinal changes and brain degeneration.
3. Preliminary results show that the assessment of retinal neurodysfunction by using microperimetry and portable ERG (RETeval) can predict cognitive decline in patients with T2D. The combination of a clinical score (DSDRS) + pupillary reactivity assessed by RETeval seems a feasible and cost-efficient examination for the screening of cognitive impairment in people with T2D over 65 years.
4. Cognitive testing was conducted using a validated neuropsychological battery tailored for the T2D population. We have found that visuo-construction is the first domain impaired in the T2D population over 65 years. In parallel, circulating blood biomarkers were investigated as non-invasive indicators of cognitive decline. Several biomarkers (i.e. pTau-217, pTau-231) have been identified in both cross-sectional and prospective studies.
5. Advanced imaging, including MRI and retinal scans, was used to assess structural and functional alterations. The 7T MRI sub-study unravelled promising candidate biomarkers. Further analysis aims to integrate clinical, imaging, and molecular data.
6. Using systems biology, the project integrated clinical, biological, and imaging data to understand disease mechanisms and develop predictive models for dementia in T2D. Although two final deliverables (D5.3 and D7.3) were delayed due to COVID-related constraints, their analyses continue beyond the project’s official close.
7. Exploitation and Dissemination: Fifteen deliverables were submitted during the final period, alongside nine open-access publications. A Business Plan, Innovation Management Plan, and Dissemination Plan were produced. The consortium actively engaged in scientific events, public communication, and social media outreach. A catalogue of exploitable results was also developed to guide future collaborations and potential commercial applications.
RECOGNISED has taken an innovative approach to understanding and predicting cognitive decline in people with T2D, using the retina as a window into brain health. By applying advanced technologies and integrating molecular, clinical, and imaging data, the project has developed a detailed profile of dementia risk in diabetic individuals and moved the field forward.
The project showed that tau protein accumulates similarly in the brain and retina of diabetic models, supporting a shared neurodegenerative mechanism. It also identified dysfunction in protein-folding systems, particularly the downregulation of Hsp90β, implicating cellular stress pathways. These insights, combined with preclinical imaging and behavioural studies, support the retina’s role as an accessible biomarker of cognitive health.
Clinically, harmonised data collection across centres enabled analysis of retinal images, cognitive scores, and blood biomarkers. The retinal parameters of neurodysfunction identified in this project and the new application of DSDRS, and new circulating biomarkers are key steps toward practical cognitive screening. While full data analysis continues, the findings significantly contribute to incorporating feasible screening methods for cognitive impairment in people with diabetes that could be further transferred to the general population.
Early identification of cognitive impairment in T2D patients allows timely interventions, better management, and reduced long-term associated costs. Retinal imaging as a scalable, non-invasive method could transform diabetic care. The discovery of shared disease pathways supports the development of targeted therapies for retinal and cerebral complications.
The project showed that tau protein accumulates similarly in the brain and retina of diabetic models, supporting a shared neurodegenerative mechanism. It also identified dysfunction in protein-folding systems, particularly the downregulation of Hsp90β, implicating cellular stress pathways. These insights, combined with preclinical imaging and behavioural studies, support the retina’s role as an accessible biomarker of cognitive health.
Clinically, harmonised data collection across centres enabled analysis of retinal images, cognitive scores, and blood biomarkers. The retinal parameters of neurodysfunction identified in this project and the new application of DSDRS, and new circulating biomarkers are key steps toward practical cognitive screening. While full data analysis continues, the findings significantly contribute to incorporating feasible screening methods for cognitive impairment in people with diabetes that could be further transferred to the general population.
Early identification of cognitive impairment in T2D patients allows timely interventions, better management, and reduced long-term associated costs. Retinal imaging as a scalable, non-invasive method could transform diabetic care. The discovery of shared disease pathways supports the development of targeted therapies for retinal and cerebral complications.