Abstract Alzheimer's Disease (AD) pathology is characterized by the accumulation of amyloid-beta (Aß) plaques and tau tangles, leading to cognitive decline. Cognitive reserve (CR), in this study...Show moreAbstract Alzheimer's Disease (AD) pathology is characterized by the accumulation of amyloid-beta (Aß) plaques and tau tangles, leading to cognitive decline. Cognitive reserve (CR), in this study estimated by educational level, is believed to mitigate the impact of these pathologies on cognitive function. This study hypothesized that at similar levels of amyloid and tau built-up, people with higher educational level show less cognitive decline overtime compared to people with lower educational level. For this we used a preclinical sample, as the non-symptomatologic stage is understudied. In a prospective study design, 217 cognitively healthy monozygotic twins over the age of 60 (mean age = 70.79, SD = 7.96) from the Netherlands Twin Register were analysed. Aß levels were assessed using PET imaging, while tau levels were measured via cerebrospinal fluid (CSF) analysis. Cognitive performance was evaluated at baseline and through three follow-up assessments over approximately six years. Linear Mixed Models (LMMs) results indicated a significant association between higher Aß levels and memory decline, with no significant impact on attention, language, or executive functioning. Higher tau levels were associated with declines in memory, attention, and language. Contrary to expectations, CR did not moderate the relationship between AD biomarkers and cognitive decline. These results suggest that while Aß and tau are linked to cognitive decline, CR estimated through educational attainment, does not provide significant protective effects in the preclinical stages of AD. This may be due to disproportionate biomarker distribution across educational groups, small sample sizes in lower education groups, and the study's cross-sectional and global biomarker measurements. Layman’s Abstract: De ziekte van Alzheimer leidt tot geheugen- en denkproblemen als gevolg van schadelijke eiwitten in de hersenen. In deze studie werd onderzocht of hoger onderwijs, waarvan gedacht wordt dat het de cognitieve reserve vergroot, bescherming kan bieden tegen deze effecten. We bestudeerden 217 gezonde oudere tweelingen en ontdekten dat hogere niveaus van deze eiwitten verband hielden met een afname van het geheugen en andere cognitieve vaardigheden. Verrassend genoeg kon hoger onderwijs deze achteruitgang niet voorkomen, wat erop wijst dat onderwijs alleen, mogelijk geen bescherming biedt tegen de vroege tekenen van de ziekte van Alzheimer.Show less
