Summary
A secondary analysis of the two-year FINGER trial found that Alzheimer’s-related blood markers were associated with cognitive trajectories, but did not significantly modify the cognitive benefit of a multidomain lifestyle intervention. The findings come from a medRxiv preprint.
A secondary analysis of the two-year FINGER randomized trial found that Alzheimer’s-related blood biomarkers were associated with less favourable cognitive trajectories in at-risk older adults, but did not significantly change who benefited from the multidomain lifestyle intervention. The analysis covered 1,260 participants and is reported in a medRxiv preprint.
The researchers measured six plasma biomarkers: amyloid beta (Aβ), phosphorylated tau 181, 217 and 231 (p-tau181, p-tau217 and p-tau231), neurofilament light (NFL) and glial fibrillary acidic protein (GFAP). The original FINGER trial had demonstrated cognitive efficacy for its intervention in an at-risk older population; this secondary analysis examined how the blood markers related to cognition and intervention response.
Biomarker levels tracked with cognitive trajectories
At the start of the study, 85% of participants had p-tau217 levels below the pathological threshold used with the Lumipulse assay. Higher levels of the measured biomarkers were associated with less favourable cognitive trajectories over the two years.
The biomarkers were less informative for one other measure: their ability to predict brain amyloid accumulation on PET scans was modest. For p-tau217, the reported area under the receiver operating characteristic curve (AUC) was 0.72. AUC describes how well a measure distinguishes between groups across possible cut-offs; a value of 0.72 indicates some discriminatory ability, rather than a definitive prediction for an individual.
Biomarker levels changed little overall during the study. The report says 82% of participants remained below the p-tau217 pathological threshold over the two-year period.
Blood markers did not distinguish intervention response
The analysis found no indication that participants’ baseline biomarker levels significantly modified the cognitive benefits of the intervention. Biomarker trajectories were also similar in the intervention and control groups.
The authors suggest that the cognitive benefits observed in this population may involve pathways not captured by the Alzheimer’s blood markers measured here. The findings therefore distinguish two questions: these markers were associated with cognitive trajectories, but their baseline levels did not significantly identify who gained more cognitive benefit from the lifestyle intervention.
The report is a secondary analysis of a randomized controlled trial and is currently a preprint. It is registered as ClinicalTrials.gov NCT01041989.