Medizinische Universität Graz Austria/Österreich - Forschungsportal - Medical University of Graz
Gewählte Publikation:
Freudenberger, P.
Predictors of brain aging
PhD-Studium (Doctor of Philosophy); Humanmedizin; [ Dissertation ] Graz Medical University; 2016. pp.
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- Autor*innen der Med Uni Graz:
- Freudenberger Paul
- Betreuer*innen:
- Schmidt Helena
- Schmidt Reinhold
- Windpassinger Christian
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- Abstract:
- The decline in a one’s mental capacities are a natural phenomenon of brain aging. Very often the cognitive decline precedes more serious diseases and results in dementia. Due to global increases in life span and aging of societies millions of people suffer from diseases associated with brain aging. The diseases underlying brain aging are complex, and influence by genetic factors, as well as many life-style choices. This thesis provides novel and original research on the topic of brain aging in three separate chapters. In chapter I the influence of maintaining a high cardiorespiratory fitness is investigated in the context of the healthy brain aging. According to our data, cardiorespiratory fitness is associated with less white matter lesions, which are hallmark of structural brain aging of vascular origin in healthy elderly. In addition, we observed higher levels of fitness to be associated with and better performance in all cognitive domains and overall cognition in the same cohort. Chapter II summarizes the current state of literature on the genetic underlying of white matter lesions and vascular dementia. In addition original research is presented on genetic polymorphisms in the NOTCH3 gene. Rare mutations in the gene are causative for CADASIL, a disease associated with early vascular brain aging and vascular stroke. We demonstrate data on four common polymorphisms in NOTCH that were associated with increase amounts of white matter lesions in hypertensive elderly. Chapter III represents my contribution to international investigations on the genetic background of brain aging. In the initial article we investigate the heritability, i.e. the amount of variance in a phenotype that is explained by genetics for intracerebral hemorrhage, a subtype of stroke. Our findings indicate that the risk of intracerebral hemorrhage, the hematoma volume and progression display high heritability and significant genetic underlying. In a follow up investigation, we present a meta-analysis of genome wide association study with intracerebral hemorrhage in Europeans. We report a novel susceptibility locus finding on chromosome 12q21.1 (rs11179580) for lobar intracerebral hemorrhage and on chromosome 1q22 (rs2984613) for non-lobar intracerebral hemorrhage. The last section of chapter III we provide a meta-analysis to identify susceptibility loci for late onset Alzheimer’s disease in over 70.000 people. We successfully identify 11 new susceptibility loci, which provide novel insight into a complex disease. In summary, both genetics and life-style influence healthy brain aging. Genetic research is crucial to determine risk factors and pinpoint molecular pathways, but they do not necessarily lead to treatments. Life-style choices, such as maintaining fitness are easily adaptable and although they might not prevent dementia, have significant impact on healthy aging overall.