Cognitive Testing, Neuroimaging, and Blood Biomarkers in the Development and Progression of Alzheimer's Disease

Abstract

Alzheimer’s disease (AD) is a progressive neurodegenerative disorder, characterized by significant loss of memory and cognitive dysfunction. It has a significant impact on an individual’s health and may financially and socially burden these individuals and their loved ones. Although the disease has been researched extensively, there is still no clear understanding of the proposed mechanisms behind the development of AD and factors aside from genetics which potentially influence the risk of developing AD. The purpose of this research is to compile and analyze data on cognitively healthy participants, participants with MCI, and participants with AD to better understand the importance of genetic risk and changes in cognitive function, bioimaging and biomarker levels, as recorded on the Alzheimer’s Disease Neuroimaging Initiative (ADNI) database. There are complex and significant relationships among these three variable groups with genetics and time. Executive function scores in healthy participants and participants with MCI were decreased with age and increased with education. In participants with AD, scores decreased over time. Language scores in healthy participants decreased with age, increased with education and for women. In participants with MCI, scores decreased with risk and time, and there was an interaction between these two variables. They also decreased with age and increased with education. In participants with AD language scores decreased over time. Memory scores in healthy participants increase with time and education and for women. In participants with MCI, scores increased with education and decreased with risk and time, and there was an interaction between these two variables. For participants with AD, there was a decrease over time. Visuospatial ability scores in healthy participants decreased with education. In participants with MCI, scores decreased with genetic risk and increased with education. In participants with AD, scores decreased over time and increased with age. Left hippocampal volume in healthy participants decreased with time, age, and education, and is increased in women. In participants with MCI, volume decreased with risk, time, age, and education. In participants with AD, volume decreased with time and age. Right hippocampal volume in healthy participants decreased with time, age, and education. In participants with MCI, volume decreased with risk and time, and there was an interaction between these two variables. Volumes also decreased with age. For participants with AD, volume decreased with risk, time, and age. Total hippocampal volume in healthy participants decreased with time, age, and education, and was increased for women. There was also an interaction between risk and time. In participants with MCI, volumes decreased with risk and time, and there was an interaction between these two variables. Volumes also decreased with age and education. For participants with AD, volumes decreased with risk, time, and age. Aβ42 levels in healthy participants decreases with risk and increased with time. In participants with MCI, levels increased with time and age, and were lower in women. In participants with AD, levels increased with time. Aβ40 levels in healthy participants increased with time and were lower for women. For participants with MCI, levels increased with time and age, and were lower for women. In participants with AD, levels increased over time. The Aβ42/40 ratio in healthy participants decreased with risk and time, and decreased with time in participants with MCI. The findings give insight into AD development and contribute to a greater understanding of longitudinal changes in AD progression. In relation to the study of AD includes the perpetuation of racial inequalities. People of color have an increased risk of developing AD and are disproportionately affected by the disease, yet are severely underrepresented in most research studies, including the research collected in the ADNI database. Racial minorities also often do not have the same access to healthcare as white people, thus contributing to the decreased possibility of early detection and treatment of AD. Black Americans, specifically, often face socio-economic barriers, which further renders the burden of AD development and progression more serious for minority families. In order to promote awareness of AD among underrepresented communities, Team Brain virtually presented to the African American Health Program, a local community of minority elders, via virtual presentations. Overall, this research concluded that hippocampal atrophy and cognitive tests appear to be the most consistent factors in the progression of MCI and AD. The analysis of blood biomarkers produced inconclusive results. This research indicates a clear set of imaging and cognitive factors that can be used to create less invasive and novel diagnostic methods for AD as well as supports the need for further research on blood biomarkers to understand their relationship with cognitive decline and progression of AD.