Abstract

The aging brain undergoes structural changes, such as brain atrophy, especially of the white and grey matter. Due to these changes, the cognition and the memory performance of elderly people decreases, but nevertheless there are considerably large differences in cognitive performance. Why some elderly people are able to maintain their memory performance relatively long despite brain atrophy still remains unclear. A mechanism called reserve is characterized by the phenomenon that a person can preserve a substantial percentage of her cognitive abilities in spite of the presence of age- or disease-related brain changes. It could be shown that in subjects without mental pathology and with similar levels of cognitive performance the degree of reserve (as measured by protective factors such as education or IQ) was associated with the degree of grey matter atrophy. These findings suggest increased compensatory ability in elderly subjects with high reserve, which allows to accrue more age-related grey matter atrophy while still holding up cognitive performance. Yet, the neural underpinnings of such compensatory effects remain largely unclear. A putative brain network supporting reserve is the cognitive control network (CCN). This particular network is of major importance for the regulation of the activity of other brain networks that are involved in mental processes like memory or attention. Within this control network especially the lateral frontal cortex (LFC), Brodman-Area 44/6, is a hub-region (a region that is highly connected with other brain regions) with a high degree of functional connectivity (FC, i.e. correlated brain activity) to an array of other brain regions. In the present study, one of the main goals was the attempt to identify the functional brain mechanisms that underlie reserve in aging subjects, which allow to mitigate the impact of grey matter atrophy on cognitive performance. Specifically, we investigated whether functional MRI assessed LFC connectivity during a memory-task is related to reserve-associated protective factors (IQ, education), and whether high LFC connectivity was associated with better mnestic parameters in relation to the respective level of grey matter atrophy. The sample consisted of 37 elderly cognitively normal subjects who consulted the memory clinic of the Ludwig-Maximilians-University Munich located at the Institute for Stroke and Dementia Research (ISD). All subjects were over 60 years old and underwent comprehensive neuropsychological testing. To assess brain activation during episodic memory, functional MRI during a face-name association task was acquired. Reserve was operationalized by years of formal education and intelligence quotient (IQ). Grey matter volume was measured within the hippocampus, a key brain region involved in episodic memory, based on volumetric T1 MRI images. Subjects performed a memory task during which the functional connectivity of the LFC was determined via psychophysiological interaction (PPI) analysis, a useful tool to investigate task-dependent changes in functional connectivity. Using various linear regression models, we focused on the question if and to what extent the functional LFC connectivity during effective mnestic encoding or recognition may be related to reserve. Reserve was defined as higher educational level and better scores in the memory tasks in relation to the stage of grey matter atrophy. Our main method was the psychophysiological interaction (PPI) analysis, a useful tool to investigate task-dependent changes in functional connectivity. The current project uses modern neuroimaging techniques to investigate functional brain mechanisms underlying reserve, which could provide further insight on how the brain manages to sustain higher levels of cognitive abilities and performance despite brain pathology. Our current findings could show that during memory processes a higher education level was related to higher LFC connectivity, which in turn predicted a better memory performance relative to the levels of brain atrophy. Higher LFC connectivity may thus be an important factor contributing to reserve.