An investigation into the structural variability of the prefrontal cortex and Its relationship to cognition and ageing

Abstract

The world is ageing at a rapid rate. Cognitive impairments, including dementia get increasingly common with age. Brain structural changes and the role of frontal cortex in cognitive ageing are well established. However, there is a paucity of research investigating differences between middle-aged adults, when cognitive difficulties are minimal, and early old-aged adults, where decline in memory are just starting to become apparent and dementia is less prevalent than during later decades. Furthermore, most studies investigating brain structure have used cortical volumes, and the associations between cortical shape changes such as cortical thickness and gyrification during ageing have not been adequately investigated.

This thesis examines the structural variability of the prefrontal regions and its relationships with cognitive function contrasting middle-aged and early old-aged groups. Analyses were undertaken using the second wave of the Personality and Total Health (PATH) Through Life Study. This study collects data on the three narrow-aged cohorts living in Canberra and Queanbeyan region (Australia) every four years. Participants were aged 40-44 and 64-68. Relationships between brain structure and cognitive function were measured using three cortical indices: cortical volume, thickness, and gyrification. Cognitive tests utilized included measures for episodic memory, processing speed, mental flexibility, working memory, and reaction times. Cortical structural measures were obtained through the use of automated brain parcellation software FreeSurfer. Structure-cognition relationships were investigated using Path analyses.

Early old-aged adults showed poorer performance in each of the cognitive domains tested. However, structure-cognition relationships varied by age-group and the structural measure utilised. While middle-aged adults showed mostly positive relationships with cortical volume, thickness, and gyrification, older adults showed mostly negative relationships with structural measures. The probability of detecting such relationships increased when more than one cortical measure was used as the use of cortical thickness and gyrification revealed significant relationships for middle-aged adults even though no such relationships had been detected using frontal cortical volume.

While the focus of the thesis was investigating how structural variability of the prefrontal cortex can affect the detection of structure-cognition relationships in middle-aged and early old-aged adults, additional investigations were also undertaken to verify the measurement of frontal structure through automated methods. The research undertaken investigated frontal cortical measurement for volume using both manual and automated methods and established that both methods provided equivalent results for measurement of absolute volume and for relationships between cognitive and demographic variables.

Research conducted demonstrated that structure-cognition relationships differ between adults of different ages. Overall, the findings suggest that different structural measures can provide separate and unique information, which capture variance of the frontal cortex and can help clarify the nature of relationships between structure and function in ageing. In addition, the significant relationships between cortical gyrification with brain volumes, cortical thickness, and cognitive functioning suggest that gyrification measures can be used as a predictor of cortical function in future structure-cognition studies. Research on the brain and cognitive ageing are fundamental in understanding cognitive ageing, so that effective strategies can be implemented to mitigate some of the adverse consequences of population ageing. Information from this thesis can be used to optimise the detection of structural correlates of cognitive function so that those with cognitive impairment are identified early and appropriate targeted interventions can follow.