Core Findings - A 14-year longitudinal study published in *Nature Medicine* indicates that walking more than 5,000 steps daily may effectively slow the progression of Alzheimer's disease in cognitively healthy older adults [1][2] - The study reveals that moderate exercise significantly reduces the accumulation rate of tau protein in the brains of preclinical patients, thereby slowing cognitive decline [1] - This research provides a clear and achievable exercise goal for older adults and opens new avenues for early intervention in Alzheimer's disease [1] Study Details - The research analyzed data from 294 cognitively intact older adults (ages 50-90) from the Harvard Aging Brain Study, including step counts, longitudinal amyloid and tau PET imaging data, and cognitive assessments over up to 14 years [1] - Increased physical activity is associated with slower cognitive decline related to amyloid plaque, indicating a protective effect of exercise [1] - The benefits of exercise are linked to the slowing of tau protein accumulation rather than changes in amyloid pathology [1] Activity Levels - Moderate activity levels of 5,001 to 7,500 steps per day are associated with stable tau protein accumulation and cognitive function [1] - Encouragingly, even light activity levels (3,001 to 5,000 steps daily) are significantly correlated with reduced tau protein accumulation and cognitive decline [1][2] Implications for Technology - The findings suggest that increasing physical activity may help delay tau pathology and cognitive decline in preclinical Alzheimer's disease [2] - The rise of digital wearable devices, such as smartwatches, makes it easier to achieve the exercise goals proposed by the study, potentially motivating sedentary older adults to engage in more physical activity [2]

Core Viewpoint - Recent innovations in Alzheimer's disease drugs have shown promising results in clinical trials, particularly the long-term efficacy of therapies like donanemab, but concerns about long-term effects and safety remain [3][4]. Group 1: Clinical Trial Results - Eli Lilly's donanemab has demonstrated a significant slowing of disease progression in Alzheimer's patients over a three-year follow-up, with early treatment showing a 27% reduced risk of advancing to the next disease stage compared to delayed treatment [3][4]. - Over 75% of early-treated patients achieved amyloid clearance within 76 weeks, and the rate of amyloid plaque re-deposition was slow at approximately 2.4 CL/year during the longest observation period of 2.5 years [3][4]. Group 2: Safety and Side Effects - No new safety signals were observed during the long-term extension phase of the study, but previously noted issues related to amyloid-targeting treatments, such as ARIA (Amyloid-related imaging abnormalities), remain a concern [4]. - ARIA-related symptoms, including edema and bleeding, primarily occur within the first six months of treatment, and patients with the ApoE4 allele are at higher risk for these complications [4]. Group 3: Market Context and Patient Demographics - Donanemab was recently introduced in China, but the long-term efficacy in the Chinese patient population is yet to be validated due to the timing of its market entry [4][5]. - The earlier launched drug, lecanemab, has also shown a 34% reduction in cognitive decline over four years, with no new safety issues reported, although this data does not include Chinese patients [5]. - China has approximately 9.83 million Alzheimer's patients, with an estimated 20% being in the early stages of the disease, indicating a significant potential market for innovative treatments [5].

Core Insights - The aging population in China is leading to an increased threat from Alzheimer's disease (AD), which has become the fifth leading cause of death in the country, following cardiovascular diseases, malignant tumors, chronic respiratory diseases, and diabetes [1] - There is a significant disease burden from Alzheimer's and other dementias in China, exceeding the global average, necessitating effective intervention measures to help patients capture the early intervention window [1] - Eli Lilly's TRAILBLAZER-ALZ2 long-term extension study results indicate that treatment with donanemab significantly slows disease progression, with benefits increasing over three years [1][2] Company Insights - Eli Lilly's TRAILBLAZER-ALZ2 study is a double-blind extension phase aimed at evaluating the long-term efficacy and safety of donanemab in early symptomatic Alzheimer's patients [2] - Participants originally receiving donanemab either continued treatment or switched to a placebo, while the placebo group began receiving donanemab under blind conditions [2] - The study included an external control group from the Alzheimer's Disease Neuroimaging Initiative (ADNI) to measure treatment outcomes [2] Study Results - Key preliminary results from the TRAILBLAZER-ALZ2 study show that participants receiving donanemab experienced sustained clinical benefits over three years, with a 0.6-point reduction in cognitive decline at 18 months and a 1.2-point reduction at 36 months on the Clinical Dementia Rating Scale Sum of Boxes (CDR-SB) [3] - Early use of donanemab reduced the risk of disease progression to the next stage by 27% compared to delayed treatment [3] - Over 75% of participants treated with donanemab achieved amyloid clearance within 76 weeks, and the rate of amyloid plaque re-deposition remained slow at approximately 2.4 CL/year over a maximum observation period of 2.5 years [3] - No new safety signals were observed during the long-term extension phase, confirming the existing safety profile of donanemab [3]