Document Type

Journal Article

Publication Title

Alzheimer's Research & Therapy


NLM (Medline)


School of Medical and Health Sciences




de Frutos-Lucas, J., Cuesta, P., López-Sanz, D., Peral-Suárez, Á., Cuadrado-Soto, E., Ramírez-Toraño, F., ... & Verdejo-Román, J. (2020). The relationship between physical activity, apolipoprotein E ε4 carriage, and brain health. Alzheimer's Research & Therapy, 12, 1-12.


BACKGROUND: Neuronal hyperexcitability and hypersynchrony have been described as key features of neurophysiological dysfunctions in the Alzheimer's disease (AD) continuum. Conversely, physical activity (PA) has been associated with improved brain health and reduced AD risk. However, there is controversy regarding whether AD genetic risk (in terms of APOE ε4 carriage) modulates these relationships. The utilization of multiple outcome measures within one sample may strengthen our understanding of this complex phenomenon. METHOD: The relationship between PA and functional connectivity (FC) was examined in a sample of 107 healthy older adults using magnetoencephalography. Additionally, we explored whether ε4 carriage modulates this association. The correlation between FC and brain structural integrity, cognition, and mood was also investigated. RESULTS: A relationship between higher PA and decreased FC (hyposynchrony) in the left temporal lobe was observed among all individuals (across the whole sample, in ε4 carriers, and in ε4 non-carriers), but its effects manifest differently according to genetic risk. In ε4 carriers, we report an association between this region-specific FC profile and preserved brain structure (greater gray matter volumes and higher integrity of white matter tracts). In this group, decreased FC also correlated with reduced anxiety levels. In ε4 non-carriers, this profile is associated with improved cognition (working and episodic memory). CONCLUSIONS: PA could mitigate the increase in FC (hypersynchronization) that characterizes preclinical AD, being beneficial for all individuals, especially ε4 carriers.



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Creative Commons Attribution 4.0 License
This work is licensed under a Creative Commons Attribution 4.0 License.