Better stress coping associated with lower tau in amyloid-positive cognitively unimpaired older adults

Abstract

Objective: Research in animals has shown that chronic stress exacerbates tau pathology. In humans, psychological stress has been associated with higher risk of Alzheimer disease clinical syndrome. The objective of this cross-sectional study was to assess the hypothesis that stress coping ability (assessed via the Brief Resilience Scale [BRS]) is associated with tau burden and to evaluate whether these associations differed by sex and amyloid status (A+/A-) in cognitively unimpaired (CU) older adults.

Methods: We included 225 CU participants (mean age 70.4 ± 10.2 years, 48% female) enrolled in the population-based Mayo Clinic Study of Aging who completed the BRS and underwent amyloid-PET (Pittsburgh compound B-PET) and tau-PET (AV1451-PET). We fitted multiple regression and analysis of covariance models to assess the associations between BRS and tau-PET and the interaction with amyloid status and sex. We focused on entorhinal cortex (ERC) tau burden and also performed voxel-wise analyses. Age, sex, education, depression, and anxiety were considered as covariates.

Results: Higher stress coping ability was associated with lower tau burden in the medial temporal lobe (including ERC) and occipito-temporal and cuneal/precuneal cortices. The association was present in both A+ and A- but weaker in A- CU older adults. There was an interaction between amyloid status and stress coping ability that was restricted to the medial temporal lobe tau such that A+ CU older adults with lower stress coping abilities showed higher tau. There were no significant interactions between stress coping and sex.

Conclusions: A faster termination of the stress response (higher coping ability) may limit the negative effects of stress on tau deposition. Conversely, lower stress coping ability may be an early sign of accumulating tau pathology. Longitudinal studies are warranted to clarify whether stress mechanisms act to exacerbate tau pathology or tau influences stress-related brain mechanisms and lowers the ability to cope with stress.

Figure 1. Results from the voxel-wise multiple regression analysis between stress coping ability and tau-PET adjusted by sex, age, and education

Maps were thresholded at p < 0.005 at voxel level and family-wise error p < 0.05 at cluster level. Significant clusters included inferior and medial temporal lobes, occipito-temporal (fusiform and lingual gyri), and cuneal/precuneus cortices. The Y axis represents the mean standard uptake value ratio (SUVR) tau-PET uptake within these regions. The X axis represents the brief resilience scale scores. Medial temporal results are shown as a binary mask overlaid into a T1 structural image.

Figure 2. Plots show the association between mean tau-PET uptake of the areas from the voxel-wise analysis (inferior and medial temporal lobes, occipito-temporal and cuneal/precuneus cortices, Y axis) and stress coping scale in amyloid-positive and amyloid-negative participants (X axis)

(A) Amyloid-positive group. (B). Amyloid-negative group. The discontinuous line in the A+ group plot (A) represents the regression line without the participant showing the lowest stress coping score (r = −0.36; p = 0.002). SUVR = standard uptake value ratio.

Figure 3. Results from the regional analyses showing an interaction between stress coping scale and amyloid status on entorhinal tau standard uptake value ratios (SUVRs) but not on inferior temporal tau SUVRs and results from the voxel-wise analyses showing an interaction between stress coping ability and amyloid status

(A) Results from the regional analyses show an interaction between stress coping scale and amyloid status on entorhinal tau SUVRs (left) but not on inferior temporal tau SUVRs (right). (B) Results from the voxel-wise analyses show an interaction between stress coping ability and amyloid status. Maps were thresholded at p < 0.005 at voxel level. Medial temporal results are shown as a binary mask overlaid on a T1 structural image. Both analyses were adjusted for age, sex, and years of education.