*4.8. Future Research Directions*

The present study suggests a potential compensatory hemodynamic mechanism in end-of-life dementia, which is sex-dependent. Those vascular adaptations observed in 3xTg-AD female mice survivors might provide clues to understand potential vascular targets for pharmacological and non-pharmacological interventions.

**Supplementary Materials:** Supplementary materials can be found at https://www.mdpi.com/2227 -9059/9/2/111/s1. Supplementary data: Mental health and cardiovascular function correlates.

**Author Contributions:** Conceptualization, L.G.-L. and F.J.-A.; methodology: behavior, asymmetry quantifications, and correlation analysis, A.M.; systolic blood pressure, E.V.; MRI-ASL-rCBF, E.J.-X.; angiogenesis, L.P.-U. and F.J.-A.; aortic function, F.J.-A.; writing—original draft: L.G.-L., F.J.-A. and A.M.; writing—manuscript: all the authors. Funding acquisition, L.G.-L. and F.J.-A. All authors have read and agreed to the published version of the manuscript.

**Funding:** This work was funded by UAB-GE-260408 to L.G.-L and SAF2014-56111 to F.J.-A. The colony of 3xTg-AD mice is sustained by European Union's Horizon 2020 research and innovation program under grant agreement No 737390 to L.G.-L.

**Institutional Review Board Statement:** The study was conducted according to the guidelines of the Declaration of Helsinki, and approved by the Ethics Committee of Departament de Medi Ambient i Habitatge, Generalitat de Catalunya (CEEAH 3588/DMAH 9452) the 8th of March 2019.

**Informed Consent Statement:** Not applicable.

**Data Availability Statement:** Not applicable.

**Acknowledgments:** We thank Frank M. LaFerla, Institute for Memory Impairments and Neurological Disorders, University of California Irvine, CA, USA for kindly providing the progenitors of the Spanish colonies of homozygous 3xTg-AD and NTg mice. Thanks to Javier Carrasco, The INc Molecular Biology Unit for corticosterone determination. The joint nuclear magnetic resonance facility of the UAB and Centro de Investigación Biomédica en Red-Bioingeniería, Biomateriales y Nanomedicina (CIBER-BBN) (Cerdanyola del Vallès, Spain), Unit 25 of NANBIOSIS.

**Conflicts of Interest:** The authors declare no conflict of interest. The funders had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript, or in the decision to publish the results.
