Importance: Women are consistently reported to experience steeper rates after an Alzheimers disease (AD) diagnosis. We tested if this could be due to a sex-specific cognitive reserve based in verbal memory. Objective: To determine whether the divergence in verbal memory trajectories from cognitively normal (CN) to AD varies by sex. Design: We employed a longitudinal cohort design (ADNI, PREVENT-AD) to model cognitive change over time in Abeta- CN participants versus Abeta+ participants that progressed to AD. Setting: The study was conducted in two longitudinal research cohorts. ADNI is multi-site initiative recruiting through clinical referrals and digital outreach, while PREVENT-AD, based at the Douglas Hospital, recruits individuals with a familial history of AD. Participants: Both ADNI and PREVENT-AD aim to characterize AD. At baseline, ADNI participants may have normal cognition (CN), mild cognitive impairment or dementia, while PREVENT-AD participants were all CN. For this study, we harmonized CN participants from both cohorts as controls and defined the AD trajectory group as Abeta+ ADNI participants diagnosed with AD at baseline or during follow-up. Main Outcome(s) and Measure(s): The main measure used in this study was the RAVLT Immediate Recall sub-scores: Total Learning (trials 1-5), Early Learning (average of trials 1-2), and Late Learning (average of trials 4-5). All results are summarized using Bayesian Highest Density Intervals (HDI) to provide estimates of parameter uncertainty. Results: The final sample 987 participants (440 AD) with an average of 3.9 +/- 2.0 follow-up visits. Females maintained normal verbal memory longer than males, with delayed decline onset of 2.7 years (Total Learning), 3.8 years (Early Learning), and 1.4 years (Late Learning). Rates of decline differed significantly by sex: females decline by 0.5/75 points per year (Total Learning), 0.1/15 points per year (Early Learning) and 0.09/15 points per year (Late Learning). Conclusions and Relevance: Female may mask early signs of AD through compensatory verbal mechanisms, delaying detection but contributing to sharper decline once symptoms emerge. Current testing paradigms need to explore assessments that are more sensitive to early cognitive change in females that move beyond reliance on verbal memory.
Neural manifolds that orchestrate walking and stopping
Walking, stopping and maintaining posture are essential motor behaviors, yet the underlying neural processes remain poorly understood. Here, we investigate neural activity behind locomotion and