Time will tell: Language and cognitive change in early Alzheimer's disease

Abstract

This dissertation employed an epidemiological approach to investigate language and cognitive changes associated with Alzheimer’s disease by leveraging longitudinal data and cohort studies. This dissertation is organized into three key sections, each addressing distinct but interconnected themes in the early detection and understanding of Alzheimer’s disease. The first section focused on biomarker-defined preclinical and prodromal impairment in language and cognition with two systematic reviews and meta-analyses that provide a comprehensive overview of existing literature. The findings of this section provided valuable insights into the cross-sectional associations of amyloid and tau burden—two established biomarkers of Alzheimer's disease—with semantic and episodic memory in older adults without dementia. The second section of this dissertation concentrated on how biological, behavioral, and sociocultural determinants can influence cognitive aging outcomes. The findings of this section show that cognitive outcomes, including trajectories over time, are subject to influences at both the micro-level (i.e., individual) and macro-level (i.e., societal factors, including the environment, society, and health infrastructure). The third section of this dissertation focused on understanding language trajectories in early stages of Alzheimer's disease. The findings of this section elucidate how language abilities evolve during the early stages of Alzheimer’s disease, with a special emphasis on semantic decline and its potential in early diagnosis and prognosis. Collectively, the nine chapters in this dissertation emphasize the power of longitudinal data: while cross-sectional approaches provide snapshots of single measurement moments, longitudinal studies allow to distinguish subtle changes over time in language and cognitive function that serve as early indicators of Alzheimer’s disease. The identification of subtle language changes in the preclinical and prodromal stages aligns with the broader acknowledgment of language impairment as an early symptom of Alzheimer's disease. This dissertation emphasized that, within the complex system of language, semantic decline plays a crucial role in the early stages of Alzheimer's disease. The findings in this dissertation contribute to theoretical advancements and provide practical insights for the development of sensitive cognitive tools that may be used for early diagnosis and aid clinical trial research. The intersection of epidemiology and neurolinguistics that this dissertation applied to investigate the complexities of language and cognitive trajectories opens the door to innovative research possibilities. Future studies can continue to explore this interdisciplinary approach, by utilizing medical statistics to analyze detailed language and cognitive assessments in relation to biomarkers to identify early cognitive markers of dementia. The studies presented in this dissertation also have broader implications for clinical practice and research, advocating for the inclusion of diverse populations in cognitive assessments, culturally sensitive metrics, and the development of tools that align with the cultural, demographic, and linguistic characteristics of different populations. The novel approaches explored in this dissertation, together with the acknowledgment of the limitations of existing cognitive assessments for detecting early Alzheimer’s disease, call for continued enhancement and innovation in the development of sensitive and inclusive cognitive tools.