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2019 Alzheimer's Association Research Grant (AARG)

Brain vulnerability and resilience during midlife

Can lifestyle factors be modified to promote brain health during midlife?

Eider Arenaza-Urquijo, Ph.D.
Barcelonabeta Brain Research Center
Barcelona, Spain


Researchers believe that there is not a single cause of Alzheimer’s but rather it develops over time as a result of multiple factors such as lifestyle, environment and genetics. Preventing or slowing disease progression may be more successful if implemented before extensive and irreversible brain changes have occurred. Studies suggest that brain changes associated with Alzheimer’s may begin a decade or more before symptoms such as changes in memory, thinking and reasoning appear. Dr. Eider Arenaza-Urquijo believes that identifying and minimizing modifiable risk factors related to cardiovascular (heart) health such as high blood pressure, during midlife could impact the later development of Alzheimer’s and other dementias.

Research Plan

Dr. Arenaza-Urquijo and colleagues will study 1500 middle-aged cognitively unimpaired adults with a family history of Alzheimer’s (these individuals have at least one parent with the Alzheimer’s and therefore at an increased risk) as a part of another ongoing study – the Alzheimer’s and Families (ALFA). Participants in this study have undergone tests that include brain scans, cognitive tests, genetic, heart health, lifestyle assessments etc. The researchers will also leverage Alzheimer’s biological marker (biomarker) information from a subgroup (400) of these 1500 participants. The biomarker information includes beta amyloid and tau protein levels in the brain from brain scans as well as cerebrospinal fluid (called CSF that surrounds the brain and spinal cord) samples.
Using these available assessments, the researchers will determine the participant’s estimated years of Alzheimer’s onset and brain changes (seen in Alzheimer’s) compared to parent’s age at symptom onset. The researchers will use sophisticated statistical models in order to quantify and measure how numerous factors such as the participant’s lifestyle, heart health, family history, brain vulnerability or resilience may contribute to the onset. The researchers will also consider which type of APOE gene (that provides instructions to make the ApoE protein, which is thought to help carry fats throughout the body) the participants possess to be another factor, since there are several variations of the APOE gene including APOE-e2, APOE-e3 and APOE-e4; possessing APOE-e4 compared to the other variations increases a person’s risk of developing Alzheimer’s. Using the statistical models, Dr. Arenaza-Urquijo’s team will determine the combination of factors that may best predict cognitive decline.


The study may shed light on risk and protective factors during midlife and provide further clues to better understand how the modification of these lifestyle factors may help slow or prevent brain changes seen in Alzheimer’s.

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