Exploration of relationships between life course measures of socioeconomic status and structural brain changes linked with older life cognitive decline

Abstract

The structure and the function of the adult human brain are shaped by socioenvironmental factors that occur across the life course. These factors may contribute towards development of structural brain changes which may be associated with dementia. Socioeconomic status (SES) is a multifaceted construct which reflects an individual's access to economic and social resources.

Disadvantaged SES has been linked with an increased risk of dementia. Examining the impact of disadvantaged SES from a life course perspective on the adult brain may present valuable insights into the aetiology of dementia. This thesis aims to bridge the knowledge gaps in understanding the relationship between life course SES and damaging structural brain changes in adults.

Within Chapter 1, I introduce SES and adult structural brain changes through the life course paradigm. I focus on two major structural brain changes; white matter hyperintensities (WMH) and total brain volume (TBV). I discuss how studying critical time periods, accumulation of risk and social mobility may present more detailed insights into the role of disadvantaged SES on adult brain structures. I overview the Lothian Birth Cohort 1936 (LBC1936) dataset.

In Chapter 2, I present a systematic review of epidemiological studies exploring life course SES and structural brain changes in adults. Among 8134 studies selected, 24 unique publications were included and discussed in detail.

Within chapters 3 and 4 I examine relationships between life course SES and WMH volume and TBV respectively amongst a cross sectional sample of 657 LBC1936 participants. An adjusted multivariable critical time period linear regression model revealed that disadvantaged older life SES was associated with greater WMH volume, β= 2911mm3,95%CI (514, 5310), p =0.0174. Downward high to low social mobility was associated with greater WMH volume, β= 3363mm3, 95% CI (1090,5640), p= 0.00379. Furthermore, an adjusted critical time period multivariable linear model revealed that midlife low SES β= -8367mm3, 95%CI (-15800, -933.80), p= 0.02745 and older life low SES, β=-8669mm3, 95%CI (-14400, -2956), p=0.00301 were associated with smaller TBV. In adjusted models, accumulation of five periods of low SES was linked with smaller TBV, β=-13160mm3 95%CI (-26300, -1.41), p= 0.050. High to low end life SES trajectory β =-20680mm3, 95%CI (-39700, -1640), p= 0.0333 or sustained low SES across three time periods β=-10500mm3, 95%CI(-19800,-1150), p= 0.0277 was linked to smaller TBV.

In Chapter 5 I replicated the multivariable linear regression analyses conducted in chapters 3 and 4 using different cut off points to represent high and low SES. My findings suggest that the findings depicted within the prior chapters were maintained under different statistical conditions. In my final chapter I overview and contextualise the findings of my systematic review and the data analysis chapters and consider the implications of my findings, policy implications and directions for future research.