Exploring frailty and cognitive functioning trajectories in later life

Abstract

Understanding the ageing process in later life is a crucial step in identifying those at highest risk of health decline, and in implementing effective prevention and treatment strategies. However, measuring the ageing process is a complex and divisive issue. As chronological age does not necessarily capture the vast heterogeneity of older age, we require the development of quantifiable health states. This thesis explored two of these states: Frailty and mild cognitive impairment. A consensus on the concept of frailty and how it should be measured remains elusive; however, it is generally understood to describe a state of higher vulnerability to adverse events such as disease, disability, dementia, and death. Mild cognitive impairment (MCI) is a health state that describes a borderland between normal cognitive functioning and dementia, exhibited by mild subjective and objective cognitive impairments but a retained independency and ability to undertake activities of daily living. This thesis explored later life ageing trajectories using these health states and ultimately sought to provide a foundation for further research and clinical care to build upon.

The first study acts as an introduction to the concept of frailty by conducting a systematic review of publications that explore frailty trajectories. After screening 8,318 publications, 25 met the eligibility criteria. Findings showed that the field has a considerable degree of heterogeneity in how studies measure frailty, the statistics they use to interpret their results, and the types of populations they sample. Despite this, some valuable conclusions can be made: as expected, frailty increases with age, and these increases are consistently associated with certain factors such as socioeconomic factors, social support, physical activity, and brain pathologies. I conclude that more longitudinal research is required in the field, specifically research that compares and contrasts the ways in which frailty is quantified.

The second study investigated the association between chronic inflammation and frailty trajectories in the Lothian Birth Cohort 1936. Using two common measures (Frailty index and Fried phenotype) and two blood-based inflammatory biomarkers (Fibrinogen and C-reactive protein), frailty is tracked over approximately 12 years. Findings showed that Fibrinogen was significantly associated with higher baseline Frailty index score (β = 0.011, 95% CI [0.002, 0.020], p < .05). Additionally, over the 12-year follow-up, higher baseline C-reactive protein (β = 0.001, 95% CI [0.000, 0.002], p < .05) and Fibrinogen (β = 0.004, 95% CI [0.001, 0.007], p < .05) were both significantly associated with increased Frailty index change. For the Fried phenotype, higher baseline inflammation biomarkers were associated with higher baseline frailty status (p < .001), but there were no significant associations over the 12-year follow-up. Accordingly, inflammation appeared to be associated with higher rates of frailty over time but the way in which you measure frailty can affect this association.

The third study aimed to explore the heterogeneity of frailty trajectories and account for the probability that not all individuals follow the same path. Using a quadratic latent class mixed model, subpopulations of frailty trajectories were identified over approximately 12 years in the Lothian Birth Cohort 1936. Analyses revealed three classes of frailty trajectories which begin at different intercepts and follow different slopes: Low (61%, n = 632), Medium (36%, n = 368), or High (3%, n = 28). Those in the Low class were younger, had higher education, higher age 11 cognitive ability, and were from a higher social class when compared to those in either Medium or High classes. These findings help to demonstrate the heterogeneous nature of frailty progression and indicate that not all older adults will follow a similar path. This has clinical implications for identifying those on steeper trajectories and implementing effective prevention strategies.

The fourth study shifted focus to the cognitive aspects of later life decline by exploring the health state known as mild cognitive impairment or MCI. This study introduced the concept and detailed how it was coded and implemented in the Lothian Birth Cohort 1936. MCI is implemented at three waves of the cohort at ages 76 (n = 567), 79 (n = 441), and 82 years (n = 341). In line with similar cohorts, rates of MCI showed an increase at each wave between 76 and 82 years from 15% to 18%. Additionally, two subtypes of MCI were derived: amnestic, which solely considered memory related cognitive decline, and non-amnestic, which considered non-memory related cognitive impairments (executive function, attention, language, and visuospatial skills). These subtypes also showed increases over time in the cohort, however, the non-amnestic subtype showed rates that were higher than expected compared to similar cohorts. This study highlighted the prevalence of MCI in the Lothian Birth Cohort 1936 and opened the door for further study of cognitive ageing trajectories.

The fifth and final study considered transitions in MCI status and the factors that may be associated with these changes in the Lothian Birth Cohort 1936. Progressions and reversions in MCI status between the ages of 76 and 82 years were assessed. At age 76, 14% of the sample had MCI, compared to 19% at age 82. Findings showed that over the six-year period, 74% remained cognitively healthy, 12% transitioned to MCI, 7% reverted to healthy cognition, and 7% maintained their baseline MCI status. Multinomial logistic regression analysis indicated that these transitions are affected by factors including age, cardiovascular disease, and number of depressive symptoms. This study illustrates the volatility of cognitive states in later life and highlights several factors, including depression, which may be associated with these changes.

This thesis provided an exploration of the ageing process by considering the trajectories of frailty and MCI in the Lothian Birth Cohort 1936. The findings contribute to an expanding field of longitudinal research, which hopes to understand how health statuses like frailty and MCI change over time, and the salient factors associated with these changes. Incremental advances like those seen in the studies in this thesis allow for a better understanding of how the ageing process affects us in later life, ultimately leading to better prevention strategies and interventions that allow every individual to follow their healthiest ageing trajectory.