In January 2020, researchers at the Barcelonaβeta Brain Research Center (BBRC) published the results of a study on the relationship between insomnia and the risk of developing Alzheimer's disease. Specifically, they discovered that people with sleeping problems present differences in cognitive performance and brain structure, especially in the white matter and some regions that are affected in early stages of Alzheimer's disease.
We spoke with the first author of this work, Dr. Oriol Grau, neurologist and researcher in the Clinical Research, Biomarkers and Risk Factors group, to learn about the evolution of this study and the new research project Alfa Sleep, which he will lead alongside the Director of the BBRC Alzheimer's Prevention Program, Dr. José Luis Molinuevo.
Broadly speaking, what do we know about the relationship between insomnia and Alzheimer's disease?
It is well known that insomnia negatively affects cognitive performance, increases the risk of cognitive decline in older ages, and also that people with Alzheimer's disease often have insomnia and other sleep disorders. What we have begun to understand better in recent years are some of the mechanisms responsible for this association, particularly the relationship between sleep quality and brain changes related to Alzheimer's disease. Everything points to the existence of a vicious circle between sleep quality and Alzheimer's: on the one hand, sleeping little and poorly would favor the accumulation of beta-amyloid and tau proteins, which we know accumulate in the brains of people with Alzheimer's disease; on the other hand, Alzheimer's disease affects from early stages regions of the brain involved in the regulation of sleep, favoring the appearance of insomnia.
Does having insomnia directly imply that we can develop the disease in the future?
No. Alzheimer's disease is the result of a very complex interaction involving many factors such as age, genetics and numerous environmental factors, many of them related to our lifestyle. Insomnia is one more among many of these risk factors, so its contribution to the total risk of suffering from the disease is surely small. Even so, it is vitally important to understand how each and every one of these risk factors affect the development of the disease, especially those on which we can act, in order to develop effective preventive strategies.
There are many factors that can affect the quality and quantity of sleep. For example, now during confinement many people have more trouble sleeping. What factors do you take into account to measure insomnia in BBRC study participants?
Sleep quality can be affected by a multitude of factors and can vary from day to day. For this reason, we use questionnaires that try to reflect the quality of sleep during a certain period of time, not a single day. Still, it is true that exceptional circumstances such as the current one affect this type of measurement and it would probably have to be taken into account in the analyzes. In fact, when we analyze the data, we always try to take into account all kinds of circumstances and factors that can influence the sleep quality. For example, people with high levels of anxiety or depression tend to sleep worse. On the other hand, we know that sleep quality worsens with age, that women are more prone to insomnia and that obesity is associated with a greater probability of sleep apnea. When analyzing the data, we always take all these variables into account to ensure that the results we find are explained by differences in the quality of sleep, and not by other factors.
What results have you obtained so far thanks to the tests carried out by BBRC participants?
We have analyzed data from 1,683 healthy people who participated in the Alfa study, which has the support of the “la Caixa” Foundation, and we have observed that the presence of insomnia is associated with poorer performance on cognitive tests. In a group of about 400 people who underwent a brain MRI we have also analyzed whether there are differences in the volume of gray matter between people with and without insomnia, and we have seen that the first ones have a lower volume of gray matter in regions that are altered early in Alzheimer's disease. Our data also suggests that there could be inflammatory changes in white matter (where we find the connections between different brain regions) related to insomnia.
In the coming months you will launch a new study on insomnia, called ‘Alfa Sleep’, thanks to two competitive projects obtained from the Alzheimer’s Association Research Fellowship Program and the Carlos III Health Institute. What will this study consist of?
In this study we take a very important step in terms of the quality of the type of information about sleep we collect, since, in addition to questionnaires, we will collect data using actigraphs, which are wristband-shaped devices that provide very accurate and reliable data about the quality and quantity of sleep. We will also invite a small group of participants to take a polysomnogram, which is the most reliable and detailed test available to study sleep. In addition, we will analyze the levels of a substance called orexin, which is key in the regulation of sleep and could be involved in the disease. This information will be added to all the data that we already collect within the Alfa+ study, which includes highly detailed clinical information, cognition tests, advanced neuroimaging and collection of blood and cerebrospinal fluid samples.
What results do you hope to obtain?
By analyzing the collected data, we will study the association between different sleep parameters and brain and biochemical changes, both in terms of their function and structure. We hope to be able to demonstrate that a lower quality of sleep is associated with higher deposits of tau and beta-amyloid proteins, and differences in brain structure and function in healthy people, as well as understanding what is the role of orexin and brain inflammation in this relationship. A good understanding of the mechanisms that link sleep and Alzheimer's is necessary in order to lay the foundations for the design of pharmacological treatments or other types of interventions aimed at preventing or treating Alzheimer's disease through an improvement in the quality of sleep.