Associations between psychological factors, grey matter volume, and resistance and resilience to tau pathology in cognitively unimpaired older adults

Abstract

AbstractBackgroundModifiable factors may influence risk for Alzheimer’s disease (AD) via two distinct, though not mutually exclusive, pathways: resistance and resilience to pathology. Whereas cognitive ‘resilience’ is defined as the maintenance of better‐than‐expected cognitive performance in the face of Aβ and tau pathology, ‘resistance’ refers to an absence or delaying of the pathology itself. We explored the potential influence of psychological factors on resistance and resilience to tau pathology in older adults at risk of AD dementia, and whether grey matter volume mediates these relationships.MethodMeasures of psychological factors (including mindfulness, optimism, purpose in life, Big‐5 personality traits, and affective symptoms), longitudinal cognitive assessments, and structural MRI scans were collected in 259 nondemented older adults, along with Aβ‐ and tau‐ positron emission tomography (PET) scans in a subset of 156 individuals. Relationships between psychological factors and entorhinal tau pathology, and between psychological factors and cognitive resilience to entorhinal tau pathology (quantified using the residuals method), were explored, controlling for age, sex, and global Aβ burden. Principal components analysis was then performed to reduce the psychological factors that were associated with resistance/resilience down to their underlying components. Relationships between the psychological components and grey matter volume were explored using voxel‐based morphometry analyses. Finally, the potentially mediating effect of grey matter volume on the relationships between the psychological components and resistance/resilience to pathology were examined.ResultOne principal component was associated with resistance to pathology, comprising mindful acting with awareness, perseverative thinking, conscientiousness, neuroticism, depression, purpose in life, and optimism. Two principal components were associated with resilience to pathology, the first comprising mindful nonjudgment, anxiety, and stress, and the second comprising extraversion and openness. These three principal components were associated with partially distinct patterns of grey matter volume, which overlapped in medial prefrontal and posterior cingulate cortices (Figure 1). Grey matter volume partially mediated the relationship between psychological factors and resistance, but not resilience, to pathology.ConclusionPsychological functioning may influence resistance and resilience to AD pathology in cognitively unimpaired older adults. Increased grey matter associated with different combinations of protective psychological factors may assist in the delaying or prevention of AD pathology.