Steeper Basal Cortisol Slopes Are Associated with Elevated Risk of Pathological Amyloid‐beta Accumulation

AbstractBackgroundThe accumulation of amyloid‐beta (Aβ) plaques, the hallmark neuropathology of Alzheimer’s disease (AD), begins several decades prior to the onset of cognitive symptoms. The progression of the disease is believed to be driven by this accumulation; therefore, there is interest in identifying factors which trigger or accelerate the aggregation of Aβ. We examined whether changes or elevations in basal cortisol levels predicted the transition to a state of Aβ‐positivity, as determined by Pittsburgh Compound B (PIB) thresholds.MethodData were utilized from the neuroimaging subset of the Baltimore Longitudinal Study of Aging. One‐hundred and fifteen middle‐aged to older adults (mean age 58.39 at baseline) with at least two 24‐hour urinary free cortisol measures collected prior to reaching the threshold for Aβ‐positivity were included.ResultA Cox regression model showed that after controlling for age, the slope of basal cortisol levels over time was significantly associated with the risk of becoming Aβ‐positive, such that each standard deviation unit increase in slope was associated with a 38% increase in Aβ‐positivity risk. Conversely, the average cortisol level during this same period was not significantly associated with Aβ‐positivity risk (HR = 1.03, p = 0.14).ConclusionThese results suggest that increases in basal cortisol levels, regardless of the average level, are associated with increased likelihood of pathological Aβ accumulation. Further investigation is warranted to determine whether basal cortisol increases directly contribute to increased Aβ accumulation and whether this mechanism can be targeted by therapeutic intervention.