Imaging the aging brain : cognitive and electrophysiological correlates

In all species, age brings a progressive slowing of brain function in virtually every domain. Our speed of processing slows down, our working memory capasity decreases, our motor functions deteriorate and our ability to form new memories is reduced. Such aging related decline is paralleled by concurrent reductions in brain volume, thinning of the cerebral cortex and expansion of the ventricular compartments, even in absense of any neurodegenerative disease. Despite these general trends, there is evidence of considerable variability between individuals. While some show a high degree of preservation of their cognitive abilities, in others neurobiological changes seen during the course of normal aging accelerate, effectively contributing to cognitive decline and dementia. Degree of cognitive deterioration in aging is determined by a dynamic interplay between a myriad of environmental and genetic factors influencing the molecular and cellular processes of aging. Thus, characterizing and understanding the aging-related alterations in the healthy human brain provide a window into the processes that at a later stage might accelerate and produce cognitive impairments characteristic for neurodegenerative disorders including Alzheimer’s disease. The main objectives of this thesis are to 1) delineate age differences in the microstructrual properties of the human brain white matter, and 2) establish links between structural and functional brain imaging and cognitive functions within the perspective of the aging brain and mind. To this end, we combine advanced neuroimaging techniques including structural magnetic resonance imaging (sMRI), diffusion tensor imaging (DTI) and electroencephalography (EEG) to delineate associations between structural and functional properties of the brain (Paper I), chart the life span trajectories of white matter microstructure and volume (Paper II), and explore relations between regional cortical thickness and cognitive performance (Paper III) in a large sample of healthy volunteers. In Paper I, we use DTI to investigate the associations between microstructural properties of the axonal pathways wiring the brain and an EEG marker of large-scale neuronal synchronization in a healthy adult sample (n=87, 40-60 years). The results support a link between brain activity and the microstructural measures, providing novel evidence of an association between structural brain connectivity and functional integration as measured by EEG within the same neuronal network. In Paper II we investigate the age-related differences in the microstructure of the brain white matter in a large healthy sample (n=484, 8-85 years). The results showed evidence of a three-phasic pattern with protracted maturation peaking around 30 years of age, followed by a relative stability in adulthood and accelerating alterations from about 65 years of age. The trajectories in general parallell life span cognitive development, and the findings support the use of DTI in studies aiming to integrate various levels of imaging and cognitive phenotypes. The attentional systems of the brain enable the organism to filter, select and extract relevant information from a noisy and often ambiguous environment. In Paper III, we test the hypothesis that cortical thickness in functionally relevant regions is sensitive to variability in specific attentional functions as measured by the Attention Network Test (ANT). The results support the findings from Paper I suggesting close associations between regional variability in brain structure and specific cognitive functions. The thesis provides novel information about the complex relationships between age, brain structure, brain function and cognition, and adds to the ongoing research efforts aiming to understand and ultimately detect, limit and treat cognitive impairments in aging.