Memory and Neurodegeneration Across the Lifespan

Abstract

The prevention and treatment of age-related memory impairment requires the early detection of underlying pathological changes and the availability of effective risk modifying intervention. This, in turn, demands research into biomarkers and risk factors of cognitive performance over the life course. Prospective cohort studies are well suited for examining biomarkers and risk factors. However, life-course approaches to cognitive performance require cognition tests that are applicable to a wide age range of participants, provide reliable and valid results after multiple administration, require limited examination time, and yield rich data to allow exploring a broad range of potential research hypotheses. When setting up the cognitive assessment battery for the Rhineland Study, a brain focused prospective cohort study which aims to investigate causes and biomarkers of healthy aging and neurodegeneration, the need for memory tasks that meet these requirements became apparent. Therefore, I aimed to develop sensitive memory measurements for use in prospective cohort studies. I successfully created nine equally difficult versions of Rey's Auditory Verbal Learning Test (AVLT), a sensitive, well-known and widely used measure of episodic verbal memory which is subject to learning effects in case of multiple testing. Furthermore, I developed a functional magnetic resonance imaging (fMRI) task that shows visual and auditory specific sensory brain activity as well as sensory-specific and -unspecific memory-encoding-associated brain activity within only ten minutes of fMRI acquisition time. Finally, we compiled the Rhineland Study cognitive assessment battery, which consists of the AVLT as our main memory examination together with other tests that examine other cognitive domains.<br /> To illustrate the use of such a cognitive assessment battery, in the second part of my thesis we examined the association between retinal layers as potential biomarkers and chronic stress as a potential risk factor of neurodegenerative processes. We found small but significant associations between the macular ganglion cell layer (mGCL) volume and global cognitive function, processing speed and episodic verbal memory independent of age and other influencing factors. Perceived stress also showed associations with all cognitive domains, especially working memory and executive functions. We conclude that mGCL volume may be a potential biomarker and perceived stress a potential risk factor for memory decline, but longitudinal studies are needed.