Abstract
INTRODUCTION: Alzheimer's disease (AD) patients with higher educational attainment (EA) often exhibit better cognitive function. However, the relationship among EA status, AD pathology, structural brain reserve, and cognitive decline requires further investigation. METHODS: We compared cognitive performance across different amyloid beta (Aβ) positron emission tomography (A ±) statuses and EA levels (High EA/Low EA). We examined the effects of Aβ plaques, tau tangles, and gray matter volume (GMV) on the relationship between EA and domain-specific cognitive decline. RESULTS: A+/High-EA individuals exhibited slower cognitive decline in global cognition and language domains than A+/Low-EA individuals. This cognitive benefit was independently and synergistically explained by reduced AD pathology, including lower Aβ and tau burdens, as well as preserved GMV. Additionally, High-EA individuals experienced a median delay of 1.9 years in the onset of significant brain atrophy among A+ individuals. DISCUSSION: These findings highlight the independent and synergistic contributions of EA-associated AD pathology and GMV alterations to longitudinal cognitive decline. HIGHLIGHTS: Alzheimer's disease (AD) individuals with high educational attainment (EA) show slower declines in global cognition and language. EA-related slower cognitive decline is linked to reduced tau and greater gray matter volume in AD. AD individuals with high EA show a median 1.9 year delayed onset of brain atrophy.