Age-related association of functional brain networks with white matter lesions and cortical thinning

Abstract

The sharp increase of life expectancy in the last decades has led to a progressive aging of the population and an increasing incidence of age-related diseases, like cerebral small vessel disease. These pathological developments are accompanied by a decline in cognitive abilities that contrasts with the benefits of increased life expectancy. Despite some efforts in the past, the relationship between structural damage in the brain, altered communication between neurons and cognitive consequences remains complex. This dissertation addresses the question of the extent to which age-related structural damage, in particular in the form of cerebral vascular lesions, influences the functional properties of the brain. To pursue this research question, a systematic literature review was conducted and supplemented with a small study of severely affected CSVD patients and a large cohort study of relatively healthy participants. A variety of study results from systematic review show evidence for a model of network dysfunction, particularly in the resting state networks, that underlies the cognitive impairment caused by white matter damage. However, the association between structural damage and altered functional connectivity showed a discrepancy between the results of small studies with severely affected patients and large cohort studies with relatively healthy participants. This contradiction is accompanied by a great heterogeneity of individual results, as well as analytical approaches and study populations, which, combined with a lack of standardisation of methods, suggest a cautious interpretation of the results. In the two subsequent studies, the functional topology of 17 CSVD patients was compared with 20 healthy controls and the influence of decreasing white matter integrity and cortical thickness on the functional connectomes of 976 relatively healthy participants was investigated. However, both the functional topology of CSVD patients and the functional connectivity of the cohort study participants were found to be independent of structural brain impairment at a global scale. Solely the part of the default mode network affected by age showed an indirect relationship with decreasing cortical thickness. These results indicate a certain resilience of neural communication to structural degeneration, whose direct influence on functional connectivity is more locally observable at the meso or micro level.