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Identifying preclinical Alzheimer´s disease in the community using a panel of biomarkers among individuals with Subjective Memory Complaints

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Investigating retinal changes as early biomarkers for dementia

As we live longer, dementia is a fast-growing socio-economic problem around the world. With no prevention or cure, IPACBIS has been developing a way to identify it earlier using retinal imaging, improving the chances for effective therapies.

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Dementia is an umbrella term that includes several disorders, with Alzheimer’s disease (AD) being the leading underlying cause. Dementia affects different cognitive functions, including memory, orientation, language and behaviour, leaving sufferers unable to perform daily tasks. The condition affects around 10 million people in Europe and is the main cause of dependency and disability in the elderly. Its prevalence is expected to double by 2030. With support from the Marie Skłodowska-Curie Actions programme, the IPACBIS project set out to detect the illness early, using retinal changes as disease biomarkers. “Results from clinical trials for drugs against AD have been disappointing, indicating that interventions are typically implemented too late. Acting earlier would increase the chance of success,” says Mercè Boada, principal investigator of the IPACBIS project.

Retinal thickness link to preclinical AD

The project host, Fundació ACE in Barcelona, has analysed the relationship between retinal changes and cognitive decline since 2014 using optical coherence tomography (OCT), a non-invasive scan of the retina. Patients are scanned during routine evaluations at the Memory Clinic, which has amassed data from over 10 000 scans. IPACBIS worked with 200 participants over 50 years old from the Fundació ACE Healthy Brain Initiative. Subjects self-reported cognitive decline, known as subjective cognitive decline (SCD). However, they all had normal scores on neuropsychological testing. It is known that AD-related changes are detectable in the brain years before cognitive decline is clinically evident. IPACBIS wanted to test whether retinal changes may indicate early stages of AD in the SCD individuals tested. This cohort underwent OCT and a 18F (PET-Florbetaben) scan to measure their brain’s levels of amyloid beta. Increased uptake of this protein is one of the neuropathological hallmarks of AD. Participants then underwent yearly reviews. Some of them showed impaired cognitive function at their neuropsychological evaluation without functional decline and no dementia. Their diagnosis was converted to mild cognitive impairment (MCI). “We wanted to know whether changes to retinal thickness at the start of the study, measured by OCT, correlated with future AD risk as indicated by elevated amyloid uptake. We also considered the relevance of changes in the retinal thickness to cognitive decline, and conversion to MCI at 24 months,” explains Marta Marquié, project fellow. The team found that those SCD individuals who had increased thickness in the inner nasal macula had a higher probability of testing positive for amyloid on first scan and after a 2-year follow-up. However, retinal thickness did not correlate with worsened neuropsychological scores or predicted conversion to MCI after 2 years. “Our study is a first step, but analysis of larger datasets of SCD individuals with amyloid biomarkers and OCT are needed before making conclusions about changes of retinal thickness present in preclinical AD, and its usefulness as AD biomarkers. We also need more normative data about thickness in different regions of the retina,” adds Marquié.

Addressing an urgent health concern

Identifying dementia earlier would benefit patients and save healthcare costs, as options to control the disease could be offered, such as lifestyle modification, clinical trials, cognitive stimulation and social resources. Patients could also make decisions about future care. The team will now focus on the vascular component of the retina – the network of blood vessels in the macular and peripapillary regions. They want to explore changes in retinal vascular density that occur in early stages of AD, and whether these correlate with vascular changes in the brain.


IPACBIS, dementia, Alzheimer’s, disease, memory, retina, diagnosis, optical coherence tomography, biomarker, amyloid beta, cognitive impairment

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