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05/10/2023 - Press release

New prognostic marker for the evolution of patients with Alzheimer's and other dementias

Researchers at the Hospital del Mar Research Institute have described, for the first time, a marker that can help predict which patients with Alzheimer's or other types of dementia will suffer a more rapid progression of the disease. The marker it is the degree of deterioration of the blood-brain barrier, which regulates exchanges between the blood and the brain and protects it from possible attacks and infections. The study is published in the journal Alzheimer's&Dementia and has also involved researchers from the Barcelonaβeta Brain Research Center (BBRC), a research centre of the Pasqual Maragall Foundation, and the CIBER on Frailty and Ageing (CIBERFES) and the CIBER on Physiopathology, Obesity and Nutrition (CIBERObn).

From left to right, Joan Jiménez Balado, Aida Fernández-Lebrero, Ángel Ois and Albert Puig-Pijoan.

The first author of the study, Dr. Albert Puig-Pijoan, researcher at the Hospital del Mar Research Institute and assistant physician at the Neurology Department of the Hospital del Mar, points out that in this study "we have been able to see if the increased permeability of the blood-brain barrier is a good predictor or if it is associated with a different prognosis in patients with cognitive impairment". Until now, few markers were available to predict which patients diagnosed with Alzheimer's or other dementias would have a more rapid progression.

To test whether the state of the blood-brain barrier serves as a predictor, more than 300 patients in the BIODEGMAR cohort at the Hospital del Mar were followed for four years. These people had been diagnosed with mild cognitive impairment or dementia, caused by different neurodegenerative diseases such as Alzheimer's or cerebrovascular disease. For their diagnosis, the clinical assessment was accompanied by a neuropsychological assessment, as well as data extracted from a lumbar puncture and a magnetic resonance imaging. Clinical visits and neuropsychological assessments were carried out during the follow-up to monitor their evolution.

These people had been diagnosed with different neurodegenerative pathologies, such as Alzheimer's or cerebrovascular disease, but also with mild cognitive impairment. In order to assess their evolution, data was extracted from a lumbar puncture, accompanied by a neuropsychological assessment and an MRI.

The results indicate that those in whom the lumbar puncture detected higher levels of albumin in the cerebrospinal fluid compared to blood levels, an indicator of increased permeability and therefore impaired protective function of the blood-brain barrier, had a more accelerated progression of the disease. In the patients analysed, the risk of accelerated disease progression increases by 8% for every 10% increase in this indicator in the cerebrospinal fluid.

The origin, vascular damage

The researchers point out that there are different clinical and biological factors that can affect the ability of the blood-brain barrier to protect the brain. The most common in the study population are being male, cardiovascular risk factors, especially diabetes, and the presence of signs of vascular damage detected by magnetic resonance imaging. "The hypothesis is that vascular damage causes this alteration in permeability, which leads to an acceleration of the cognitive deterioration caused by the disease that causes dementia," explains Dr. Ángel Ois, the last signatory of the study, a researcher at the Hospital del Mar Research Institute and a neurologist at the Hospital del Mar.

One of the advantages of this marker is that it is relatively simple to test albumin levels in cerebrospinal fluid and blood. This makes it a good indicator that opens the door to investigating new approaches to slow the progression of these diseases. This means that it is important to focus on cardiovascular protection factors in order to preserve the protective capacity of the blood-brain barrier, or research to find treatments to restore it in order to improve the prognosis of patients. Dr. Puig-Pijoan points out that the results obtained "indicate that vascular risk factors and cerebrovascular damage are two of the main mechanisms involved in cognitive deterioration, not only in Alzheimer's disease. Therefore, focusing on the prevention of these risk factors and potentially having targeted therapies could be a very interesting avenue to explore”.

The research will continue with larger and more specific cohorts to validate this marker in different pathologies and to search for new variables to establish the rate of evolution of people diagnosed with some type of dementia. This study may also allow a more careful follow-up of patients depending on their condition, even in those with mild cognitive impairment but without a definite diagnosis.

Reference article

Puig-Pijoan, A, Jimenez-Balado, J, Fernández-Lebrero, A, et al. Risk of cognitive decline progression is associated to increased blood-brain-barrier permeability: A longitudinal study in a memory unit clinical cohort. Alzheimer's Dement. 2023; 1-11. https://doi.org/10.1002/alz.13433

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