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.
