More evidence on the clinical utility of blood-based biomarkers for Alzheimer’s disease

Higher Alzheimer’s disease blood­-based biomarker levels may lead to faster cognitive decline, but specific cognitive domains have not been tied clearly to specific biomarkers. The resear­chers of this clinic-­based prospective study evaluated whether Alzheimer’s disease blood-­based biomarkers affected cognitive and functional trajectories in individuals aged 60 years or older with subjective cognitive complaints or mild cognitive impairment. At baseline, participants were free of dementia; blood biomarker measurements included amyloid­beta 40 and 42, phosphorylated tau (p­tau181) and neurofilament light chain (NfL) levels. Cognitive assessments, conducted annually for five years, included performance on global cognition, verbal episodic memory, semantic fluency, cognitive flexibility, mental shifting and task switching. Other outcomes included physical performance and activities of daily living.

Among 1938 participants (mean age, 73 years; 61% women), 273 developed dementia and 68 died during follow up. Higher baseline p-­tau181 concentrations led to significantly faster decline in most cognitive, physical and functional out­comes. Higher baseline NfL concentra­tions were associated with faster decline in global cognition, verbal episodic memory, semantic fluency and activities of daily living. Participants with higher concentra­tions of both p­-tau181 and NfL had steeper declines in cognitive and functional trajectories than those with only one elevated biomarker. Lower amyloid-­beta 42/40 ratios were associated with slightly accelerated cognitive declines in verbal episodic memory and semantic fluency performance. These associations were not modified by APOE-­e4, sex or education level.

Comment: The results of this study support using blood-­based biomarkers in the clinic to identify patients with subjective cogni­tive complaints or MCI who may be at risk for faster cognitive, physical and functional decline. Future studies that include phosphorylated tau­-217, another blood­-based Alzheimer’s disease biomarker not included in this analysis, also may inform these clinical trajectories.

Jennifer Rose V. Molano, MD, Associate Professor, Department of Neurology and Rehabilitation Medicine, The University of Cincinnati, Ohio, USA.

Grasset L, et al. Associations between blood-based biomarkers and cognitive and functional trajectories among participants of the MEMENTO cohort. Neurology 2024; 102: e209307.

This summary is taken from the following Journal Watch title: Neurology.