Resumen de Impact of alzheimer's disease risk factors on white matter hyperintensities and cognition in cognitively unimpaired individuals
White matter hyperintensities (WMH) have been associated with increased risk and progression of Alzheimer’s disease (AD). However, the range to which this association can be extended to AD risk factors and WMH burden in cognitively unimpaired (CU) middle-aged individuals has not yet been fully explored. Thus, the main goal of this thesis is to study how AD risk factors impact on WMH burden in CU middle-aged participants. In addition, we aim to explore the mechanisms by which WMH impact on cognition. We gathered clinical data, lifestyle habits, cognitive assessments and MRI acquisitions in a sample of more than 500 CU middle-aged individuals. The results show that despite the low WMH burden and a low prevalence of AD risk factors in the participants, AD risk factors were associated with a higher WMH burden. Regionally, WMH burden showed an impact on cognition in CU middle-aged individuals. Finally, it was found that WMH volume mediates the relationship with cortical gray matter volume in regions involved in executive functioning. The main conclusion of this study is that even very low levels of AD risk factors have a significant impact on brain structure and cognition in CU individuals. These findings support the control of modifiable AD risk factors in individuals at higher risk of developing WMH as a practical way to reduce or delay the onset of dementia.
