​​Focus: Effect of reducing brain Aβ plaque on cognitive and functional decline Alzheimer’s disease (AD) patients. Method: Instrumental variable meta-analysis.

Finding: “This meta-analysis provides statistically significant evidence of a likely causal relationship between a reduction in Aβ plaque and a reduction in cognitive and functional decline in patients with AD.“

Limitation: Combining individuals with varying stages of AD may complicate result interpretation.

​​Focus: Does altering lymphatic drainage enhance the effectiveness of antibody treatments targeting amyloid-beta in a mouse model of early-onset AD?

Method: Removing lymphatic vessels or boosting with a growth factor and measuring Aβ accumulation.

Finding: Impaired lymphatic drainage increases Aβ and inflammation.

​​Focus: Exploring gait changes in patients with mild cognitive impairment and the relationship between their gait performance and AD plasma biomarkers, specifically Aβ and p-tau181.

Method: This study recruited 231 participants with normal cognition or mild cognitive impairment and stratified them based on plasma p-tau181 and Aβ42/Aβ40 levels to analyze the association between AD plasma biomarkers, neuropsychological performance, and gait changes using quantitative motion assessment.

Findings:
1. High plasma p-tau181 levels are significantly associated with decreased stride length
2. No significant association between stride length and Aβ42/Aβ40 levels
3. Plasma p-tau181 has potential as a biomarker for tau-related motor dysfunction in MCI.

Limitation: A larger sample size is needed, and longitudinal studies are required to complete and enrich the research.

​​Focus: The study focuses on demonstrating whether glymphatic transport in humans can be pharmacologically enhanced and if such enhancement improves the brain-to-blood clearance of Alzheimer’s disease-related proteins, specifically amyloid β (Aβ) and tau.

Method: The study utilized two cross-over clinical trials in healthy older adults: one testing intravenous dexmedetomidine and the other a fixed-dose combination (ACX-02) of intravenous dexmedetomidine and oral midodrine, each compared to a placebo. Participants underwent a 4-hour and 15-minute sleep opportunity, during which physiological determinants of glymphatic function were monitored and brain-to-blood clearance of Alzheimer’s disease-related proteins (Aβ and tau) was measured.

Finding: A key finding of the study is that pharmacological enhancement of glymphatic transport is achievable in humans and significantly increases the brain-to-blood clearance of Alzheimer’s disease-related proteins, Aβ and tau.

Limitation: One study limitation is that the participants were healthy older adults without established Alzheimer’s pathology or sleep disturbances, and the biomarker effects were measured after only a single intervention.