To date, there is a considerable heterogeneity of methods to score Allostatic Load (AL). Here we propose a comprehensive algorithm (ALCS) that integrates commonly used approaches to generate AL risk categories and assess associations to brain structure deterioration. In a cohort of cognitively normal mid-life adults (n = 620, age 51.3 ± 5.48 years), we developed a comprehensive composite for AL scoring incorporating gender and age differences, high quartile approach, clinical reference values, and current medications, to then generate AL risk categories. Compared to the empirical approach (ALES), ALCS showed better model fit criteria and a strong association with age and sex. ALSC categories were regressed against brain and white matter hyperintensity (WMH) volumes. Higher AL risk categories were associated with increased total, periventricular, frontal, and left parietal WMH volumes, also showing better fit compared to ALES. When cardiovascular biomarkers were removed from the ALSC algorithm, only left-frontal WMHV remained associated with AL, revealing a strong vascular burden influencing the index. Our results agree with previous evidence and suggest that sustained stress exposure enhances brain deterioration in mid-life adults. Showing better fit than ALES, our comprehensive algorithm can provide a more accurate AL estimation to explore how stress exposure enhances age-related health decline.

Only few studies of Allostatic Load (AL) have been conducted in Latin-American cohorts. Here, we replicated a recently proposed comprehensive algorithm (ALCS) to derive an AL index in a Chilean cohort of cognitive healthy adults. Using data from the GERO cohort (n = 166, age 76.92 ± 5.07 years) we generated an ALCS AL index through and compared for model fit with a purely sample distribution l algorithm (ALES). ALCS largely improved when some clinical values were corrected for ages ≥65, although failed to achieve sufficient goodness of fit. A final inclusion of an additional inflammatory biomarker resulted in further improvement of ALES, but not on ALCS. The ALES algorithm, which do not include clinical thresholds, achieved satisfactory fit after correcting for sample disparities between sexes. This suggests the need to consider the suitability of clinical thresholds developed in younger populations and the need to develop specific thresholds for assessing older adults.

Objectives: We assessed the modulation of allostatic load (AL) by engagement in healthy habits and life stressors, mediated through resilience and the perceived influence of the stressors. Sleep was included as third mediator given extensive evidence associating to all the analysed factors.Methods: Structural equation models to assess the modulation of AL by either traumatic or psychosocial stressors and healthy habits were generated with data from 620 mid-life adults (age 51.3 ± 5.48 years). Model 1 included self-reported life stressors, engagement in cognitive and physical activities, resilience and a pyramid score for diet. In Model 2, self-reported sleep quality was included in the mediation analysis between resilience and perceived stress on AL.Results: Direct effects of sports and diet on AL, and on resilience by sports were found in all the evaluated models. The modulation of AL by both types of stressors was only revealed in model 2, through indirect effects of perceived influence via sleep quality. An effect of sport habits on AL via resilience was found to be mediated by sleep, and equivalent but opposed effects of perceived influence of stressors and resilience on sleep quality emerged as critical factor for AL modulation.Conclusion: Our results suggest that sleep plays a pivotal role in the modulation of AL by both life stressors and sport habits, balancing the harmful and protective effects of perceived stress and resilience. The relative weight of one over the other to worsen or improve sleep quality will determine the resulting level of AL.

Intrinsic capacity (IC) is a composite that includes five different domains related to a person’s capacities: sensory, locomotion, vitality, psychological and cognitive. IC represents part of a global effort to promote healthy ageing, one aspect of which is healthy cognitive functioning. This study aimed to elucidate the association of IC and cognitive decline in older adults. Using data from the English Longitudinal Study of Ageing (ELSA, wave 6), IC composite was derived through z-score and item-response theory (IRT) methods in a sample of cognitively normal older adults ( n = 731, aged 70.1 ± 6.77 years). Global cognition (GC) was derived by categorizing Mini-mental State Examination scores obtained in the same population 4–5 years later (ELSA-HCAP, 2018). After algorithm selection, GC categories were regressed on IC scores, demographic and lifestyle covariates. The IRT algorithm showed better model fit and strong associations with age, sex and education. Lower IC was associated with higher likelihood of developing mild cognitive impairment (MCI) 4 to 5 years after IC assessment. Increased age and lower education were also strong predictors of GC, whereas no significant effects were found for sex, physical activity, or number of comorbidities in the fully adjusted model. Although bivariate regressions showed that reduced moderate or vigorous physical activity and increased number of comorbidities are associated with higher odds of developing later MCI, the lack of associations between these covariates and GC in the fully adjusted model suggests a possible mediation effect on IC. No study had previously explored the association of IC on later cognitive impairment. Results agree with previous evidence associating low IC to females, older ages and lower education. Further research to reveal possible underlying mechanisms explaining this association is needed to improve our understanding and relevance of IC for healthy ageing.

To date, there is a lack of universally agreed values to calculate an Allostatic Load (AL) index and a considerable heterogeneity of methods. In this study we propose a comprehensive algorithm that integrates several approaches and generate risk categories to assess associations between AL and brain structure deterioration. In a cohort of cognitively normal mid-life adults (n = 620, age 51.3 ± 5.48 years), we developed a comprehensive composite for AL scoring incorporating gender and age differences, high quartile approach, up-to-date clinical reference values, and current medications, enabling us to then categorize individuals as no-risk, low-risk, medium-risk and high-risk of AL. Compared to the empirical approach, the comprehensive composite showed better model fit criteria and a strong association with gender. AL categories were regressed against Magnetic Resonance Imaging brain volume and white matter hyperintensity (WMH) measurements. Higher AL risk categories were associated with increased total, periventricular, frontal, and left parietal WMH volumes. This suggests that sustained stress exposure enhances brain deterioration in mid-life adults, potentially accelerating later development of cognitive decline and dementia. Showing better model fit than the classical approaches, our comprehensive algorithm can provide a more accurate AL estimation to explore how stress exposure enhances age-related health decline.