Structural changes in the brain of patients with Alzheimer’s begin 20 years before the symptoms onset

Structural brain changes in Alzheimer’s disease

Brain alterations in Alzheimer’s disease patients begin years before symptoms appear and a clinical diagnosis can be made. The neuroimaging team in our group has developed a technique that measures the movement of water particles in the cerebral cortex and makes it possible to detect structural changes in the brain up to 20 years before the diagnosis of the disease.

The study, the result of collaboration between the Sant Pau Memory Unit, the Hospital Clinic de Barcelona and the international consortium DIAN (The Dominantly Inherited Alzheimer Network) has been published in the journal Alzheimer’s & Dementia: The journal of the Alzheimer’s Association.

What have we done in this study?

In this work, we analyse cerebral magnetic resonance images of more than 300 participants that carry a genetic mutation that causes Alzheimer’s disease. The images were acquired years before they developed any symptoms. Given that the age of symptoms onset is similar in people carrying the same mutation, it was possible to estimate at what point in their life they would develop the first symptoms of the disease. We processed their brain magnetic resonance images to quantify structural measures of cortical thickness and microstructural cortical diffusivity.

Structural changes Alzheimer - Sant Pau Memory Unit - Barcelona

Main results of the study

Applying a mathematical modeling, we observed that, contrary to what was believed until now, the cortical changes follow a biphasic model. In very early stages of the disease, we observe an increase in cortical thickness and a decrease in diffusion that begins 20 years before clinical symptoms. When the participants approached the onset of clinical symptoms, a decrease in cortical thickness and increases in diffusivity were observed. These changes are associated to the deposit of amyloid and tau proteins in the brain.

Structural changes Alzheimer - Sant Pau Memory Unit - Barcelona
Relevance of the study

Many of the treatments for Alzheimer’s disease currently under development are targeted to the earliest stages of the disease, where they are most likely to be effective. Having as accurate a knowledge as possible about what happens in the brain during these early stages of the disease will allow us to assess whether a drug works or not. In this study, we propose a model that is congruent with the pathophysiological changes of the disease that could help evaluate the effectiveness of new drugs for Alzheimer’s disease.

More information

This work has been funded by national organizations (Instituto de Salud Carlos III, CIBERNED, Generalitat de Catalunya) and international organizations (National Institute of Health).

Biphasic cortical macro- and microstructural changes in autosomal dominant Alzheimer’s disease. Montal, V, Vilaplana, E, Pegueroles, J et al. Alzheimers Dement 2020

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