Understanding and potentially reversing memory decline necessitates a comprehensive examination of memory's evolution throughout life. Traditional memory assessments, however, suffer from a lack of comparability across different age groups due to the diverse nature of the tests employed. Addressing this gap, our study introduces a novel, ACT-R model-based memory assessment designed to provide a consistent metric for evaluating memory function across a lifespan, from 5 to 85-year-olds. This approach allows for direct comparison across various tasks and materials tailored to specific age groups. Our findings reveal a pronounced U-shaped trajectory of long-term memory function, with performance at age 5 mirroring those observed in elderly individuals with impairments, highlighting critical periods of memory development and decline. Leveraging this unified assessment method, we further investigate the therapeutic potential of rs-fMRI-guided TBS targeting area 8AV in individuals with early-onset Alzheimer’s Disease—a region implicated in memory deterioration and mood disturbances in this population. This research not only advances our understanding of memory's lifespan dynamics but also opens new avenues for targeted interventions in Alzheimer’s Disease, marking a significant step forward in the quest to mitigate memory decay.

Alterations in sleep are hallmarks of the ageing process and emerges as risk factors for Alzheimer’s disease (AD). While the fine-tuned coalescence of sleep microstructure elements may influence age-related cognitive trajectories, its association with AD-related processes is not fully established. We investigated whether sleep arousals and the coupling of spindles and slow waves, key elements of sleep microstructure, are associated with early amyloid-beta (Aβ) brain burden, hallmark of AD neuropathology, and cognitive change at 2 years in 100 late-midlife healthy individuals. We first found that arousals interrupting sleep continuity were positively linked to Aβ burden, while, by contrast, the more prevalent arousals upholding sleep continuity were associated with lower Aβ burden and better cognition. We further found that young-like co-occurrence of spindles and slow-depolarisation slow waves is associated to lower burden of Aβ over the medial prefrontal cortex and is predictive of memory decline at 2-year follow-up. We provide empirical evidence that arousals are diverse and differently associated with early AD-related neuropathology and cognition. We further show the altered coupling of sleep microstructure elements that are key to its mnesic functions may contribute to poorer brain and cognitive trajectories. The presentation will end with preliminary data show that activity of the locus coeruleus, essential to sleep and showing some of the earliest signs of AD-related pathological processes, is associated with sleep quality. These preliminary findings are the first of a project ailed at link sleep and AD through the locus coeruleus.

Episodic memory performance decreases with advancing age. According to theoretical models, such memory decline might be a consequence of age-related reductions in the ability to form distinct neural representations of our past. In this talk, I want to present our new age-comparative fMRI study investigating age-related neural dedifferentiation across different representational levels. By combining univariate analyses and searchlight pattern similarity analyses, we found that older adults show reduced category selective processing in higher visual areas, less specific item representations in occipital regions and less stable item representations. Dedifferentiation on all these representational levels was related to memory performance, with item specificity being the strongest contributor. Overall, our results emphasize that age-related dedifferentiation can be observed across the entire cortical hierarchy which may selectively impair memory performance depending on the memory task.