Association between Longitudinal Cerebrospinal Fluid Alzheimer's Biomarkers and the Lifestyle for Brain Health (LIBRA) Index: Findings from the European Prevention of Alzheimer's Dementia Cohort Study (EPAD LCS)

Abstract

Background: In the absence of preventative pharmacological interventions for Alzheimer's Disease dementia, there is a growing interest in modifiable risk factors associated with AD. Such risk factors are thought to contribute up to 40% of the risk of dementia. The Lifestyle for Brain Health (LIBRA) index, a dementia risk score which focuses exclusively on modifiable factors, has been found to be associated with increased risk of dementia and cognitive decline. It is currently unclear how the LIBRA index relates to cerebrospinal fluid (CSF) biomarkers of Alzheimer's Disease.

Objectives: To examine the association between LIBRA index scores and trajectories of phospho-tau 181 and total tau in the European Prevention of Alzheimer's Dementia Longitudinal Cohort Study (EPAD LCS), and to examine whether these trajectories differ between participants with high and low CSF amyloid-beta 1-42 (Aβ42).

Design: Analysis of CSF biomarker and LIBRA index scores from the European Prevention of Alzheimer's Dementia Longitudinal Cohort Study.

Setting: The European Prevention of Alzheimer's Dementia Longitudinal Cohort Study is a multi-centre, pan-European study.

Measurements: Cerebrospinal fluid samples were taken by lumbar puncture and analysed using electrochemiluminescence. LIBRA index scores were calculated from self-reported variables, questionnaires, and physiological measurements.

Result: In the total sample (n = 1715; mean age = 66.0, 56.4% female), there were no significant associations between LIBRA scores (mean = 0.73 points) and rate of change in cerebrospinal fluid biomarkers. In participants with high Aβ, reflecting less deposition in the brain, (n = 1134), LIBRA scores were significantly associated with the rate of change in total tau, where higher LIBRA scores (denoting higher dementia risk) were associated with increases in t-tau. There were no significant associations between LIBRA scores and change in cerebrospinal biomarkers in participants with low Aβ.

Conclusion: We found an association between modifiable risk factors and total tau accumulation in participants without dementia and without Aβ accumulation. This suggests that increasing levels of total tau may be driven by factors other than Aβ accumulation and highlights the need for developing and examining tau-targeting drugs in Alzheimer's Disease development.

Keywords: Biomarkers; dementia; lifestyle; risk-factors.