Resistance, brain and cognitive resilience to ATN in a memory clinic population

Abstract

AbstractBackgroundBrain resistance (R) has been defined as the capacity of the brain to preserve its integrity and to sustain normal cognition despite aging. Resilience has been defined as the capacity to sustain a better‐than‐expected brain integrity (brain resilience,BR) or cognitive performance (cognitive resilience,CR) in presence of pathological burden. There is a high variability in the individuals’ R, BR or CR, and it has been demonstrated that individuals with high BR and CR develop symptoms later than those with low CR. The aim of this study was to investigate the association between demographics, clinical features, and blood measures and individual’s R, BR and CR. Moreover, we investigated the cognitive longitudinal trajectories of individuals with low and high R, BR and CR.Method166 patients from the Geneva Memory Center cohort (41 controls, 106 MCI, 19 dementia) who underwent amyloid‐PET (A), tau‐PET (T), MRI (N) and clinical and neuropsychological assessment were included. Linear regression models were performed to extract residuals, used as measures of individual R (age predicted by ATN), BR (thickness by AT), and CR (MMSE by ATN). The associations between R, BR, CR and demographics, clinical features, blood measures were investigated using linear models. Moreover, linear mixed models were performed to examine whether longitudinal changes in MMSE scores differed as a function of R, BR or CR.ResultMean age was 71 (8), 52% were female, mean years of education was 14 (4). Resistance predicted by ATN was positively associated with plasma NfL (β=0.50,p<0.001) and GFAP (β=0.32,p=0.007). Brain resilience predicted by AT was associated with gender (higher in males) and, yet not significantly, age (β=0.14,p=0.063). Cognitive resilience predicted by ATN was associated with age (β=0.18,p=0.020) and education (β=0.27,p<0.001). Individuals with low cognitive resilience had a lower MMSE scores at baseline but those with higher cognitive resilience showed a faster cognitive decline.ConclusionWe confirm the expected associations between BR, age and gender, and between CR and age and education, consistent with previous literature findings. The association between R and plasma markers opens novel perspectives for screening and preventive programs while the assessment of the effect of plasma biomarkers on resistance needs further investigation.