This paper aims to determine whether APOE4 genotype and AD-related pathological load in the form of CSF-derived Aβ and tau can be used for prediction of mnemonic discrimination performance in cognitively healthy, non-demented elderly. Alzheimer's disease (AD) affects millions worldwide, primarily in the elderly population. To date, virtually all drug therapies have failed to effectively treat AD. Subjects carrying the APOE4 gene are known to be at up to 12-times increased risk for AD. The underlying pathological changes in the form of β-amyloid plaques (Ab) and tau tangles are detectable two decades before symptoms of memory decline arise and can be measured in cerebrospinal fluid (CSF). Early detection of AD in cognitively normal elderly would open a window of opportunity for treatment and preventative measures. This study aims to determine whether APOE4 genotype and AD-related pathological load in the form of CSF-derived Ab and tau can be used for prediction of mnemonic discrimination performance in non-demented elderly.
The global prevalence of Alzheimer’s disease and other dementias was 43.8 million in 2016 and is likely to exceed 152 million by 2050. It affects 40 % of individuals above 85 and is characterised by episodic memory decline, confusion, as well as other cognitive deficits in later stages of the disease. This global epidemic is estimated to cost over 1 trillion US Dollar, creating a serious burden for healthcare systems worldwide. At an earlier stage, Mild Cognitive Impairment (MCI) describes abnormal forms of cognitive decline that have not reached the severity of dementia. MCI affects approximately 16-20 percent of elderly aged 65 or above and 24-32 % of individuals with MCI progress to dementia. In contrast to MCI, the diagnosis of dementia requires low performance of one or more cognitive domains with significant interference in everyday activities. AD is more prevalent in women, who make up two-thirds of all cases in the US. Further, African Americans are twice as likely and Hispanics one-and-a-half times as likely to be diagnosed with AD than Caucasians. While biological differences play a partial role, for example through a stronger AD-association with the ABCA7 risk gene in African Americans, socioeconomic characteristics such as education level are more likely to drive this disproportion. Further, African Americans have a higher prevalence of diabetes, obesity and hypertension, all of which are associated with AD.
Table of Contents
Introduction
Materials and Methods
Results
Discussion
Conclusion
Objectives and Research Themes
This study aims to investigate the potential association between the APOE4 genotype, Alzheimer's-related pathological markers (Aβ and tau) in cerebrospinal fluid (CSF), and performance in mnemonic discrimination tasks among cognitively normal elderly individuals.
- Analysis of the impact of APOE4 genotype on cognitive performance.
- Examination of CSF-derived biomarkers as predictors for mnemonic discrimination.
- Evaluation of age-related effects on cognitive sub-domains (object, spatial, temporal).
- Exploration of the link between specific neuropathological markers and cognitive decline.
Excerpt from the book
Introduction
The global prevalence of Alzheimer's disease (AD) and other dementias was 43.8 million in 2016 and is likely to exceed 152 million by 2050 (1-3). It affects 40% of individuals above 85 and is characterised by episodic memory decline, confusion, as well as other cognitive deficits in later stages of the disease (4). This global epidemic is estimated to cost over US$1 trillion, creating a serious burden for healthcare systems worldwide (3).
At an earlier stage, Mild Cognitive Impairment (MCI) describes abnormal forms of cognitive decline that have not reached the severity of dementia. MCI affects approximately 16-20 percent of elderly aged 65 or above and 24-32% of individuals with MCI progress to dementia (5, 6). In contrast to MCI, the diagnosis of dementia requires low performance of one or more cognitive domains with significant interference in everyday activities (7). AD is more prevalent in women, who make up two-thirds of all cases in the US (3). Further, African Americans are twice as likely and Hispanics one-and-a-half times as likely to be diagnosed with AD than Caucasians. While biological differences play a partial role, e.g. through a stronger AD-association with the ABCA7 risk gene in African Americans, socioeconomic characteristics such as education level are more likely to drive this disproportion. Further, African Americans have a higher prevalence of diabetes, obesity and hypertension, all of which are associated with AD (3, 8, 9).
Summary of Chapters
Introduction: Outlines the rising global prevalence of Alzheimer's disease and the critical need for biomarkers that can predict early cognitive decline in preclinical stages.
Materials and Methods: Details the recruitment of 37 non-demented older adults, the procedures for APOE4 genotyping, CSF collection, and the implementation of mnemonic similarity tasks.
Results: Presents the statistical findings, noting that age significantly predicted performance in object-based tasks in females, while APOE4 status did not significantly influence mnemonic discrimination.
Discussion: Interprets the study findings within the context of existing literature, highlighting limitations such as sample size and the potential influence of high education levels among participants.
Conclusion: Summarizes that APOE4 and CSF markers were insufficient to explain variance in mnemonic discrimination performance, emphasizing the need for longitudinal and multivariate research.
Keywords
Alzheimer's disease, APOE4, cerebrospinal fluid, mnemonic discrimination, cognitive decline, biomarker, memory, amyloid-beta, tau, neurodegeneration, hippocampus, preclinical AD, aging, episodic memory, pattern separation.
Frequently Asked Questions
What is the primary focus of this research?
The research investigates whether APOE4 genotype and specific biomarkers found in cerebrospinal fluid, such as amyloid-beta and tau, can predict cognitive performance in mnemonic discrimination tasks in a non-demented elderly population.
What are the central thematic areas?
The central themes include the progression of preclinical Alzheimer's disease, the role of genetic risk factors (APOE4), the utility of CSF-based biomarkers, and the sensitivity of memory sub-domains like object, spatial, and temporal discrimination.
What is the main research question?
The study asks whether APOE4 genotype and AD-related pathological loads in the form of CSF-derived Aβ and tau can serve as reliable predictors for mnemonic discrimination performance in cognitively healthy older adults.
Which scientific methods were employed?
The study utilized a cross-sectional approach, involving CSF lumbar punctures for biomarker analysis, APOE4 genotyping via PCR, and behavioural cognitive assessments using the Mnemonic Similarity Task (MST).
What does the main body cover?
The main body covers the theoretical background of Alzheimer’s disease, detailed recruitment and testing protocols, statistical analyses of performance data, and an interpretation of how these factors relate to underlying pathology.
Which keywords characterize this work?
Key terms include Alzheimer's disease, APOE4, cerebrospinal fluid, mnemonic discrimination, cognitive decline, amyloid-beta, tau, and pattern separation.
Did the APOE4 genotype significantly influence the study outcomes?
The study found no statistically significant difference in mnemonic discrimination performance between APOE4-positive and APOE4-negative subjects within the analyzed sample.
How does age affect the results observed in this study?
The analysis indicated that age was a predictor for performance in object discrimination tasks specifically in female subjects, but it did not have a significant impact on other measured cognitive domains.
- Arbeit zitieren
- Faissal Sharif (Autor:in), 2019, Effect of APOE4 genotype and Alzheimer’s-related cerebrospinal fluid markers on cognitive decline in non-demented elderly, München, GRIN Verlag, https://www.grin.com/document/508573
