Background Allostatic load (AL) is the cumulative burden of chronic stress and life events. It involves the interaction of different physiological systems at varying degrees of wear and tear. When environmental challenges exceed the individual’s ability to cope, allostatic overload ensues. AL, a measure of the physiological ‘cost’ identified using biomarkers and clinical criteria, has been associated with socioeconomic gradients in coronary heart disease, but no studies have investigated the potential link with neurodegenerative conditions such as dementia.

This work aims to evaluate the associations between allostatic load (AL), with subsequent coronary heart disease (CHD) and dementia during a 12-year follow-up in participants from the English Longitudinal Study of Ageing.

Methods Participants (N= 4,335) were aged ≥50 years at baseline. The AL index included five biomarker risk groups covering neuroendocrine (Insulin growth factor 1), cardiovascular (systolic and diastolic blood pressure, resting pulse rate, medication), metabolic (total cholesterol-to-HDL ratio, HbA1c, triglycerides), immune (C-reactive protein, fibrinogen) and anthropometric systems (waist-to-height ratio, obese) as measured at baseline. Except for obesity, the highest gender-specific quartile of the distribution for each biomarker was scored with 1, while the remaining groups with 0. The sum ranged from 0 to 12, with higher scores signifying higher AL, and was grouped into 3 categories: 0 (reference group), 1–3 and 4+. CHD events were defined as myocardial infarction and angina. Dementia was determined by doctor’s diagnosis combined with a positive score on the Informant Questionnaire on Cognitive Decline in the Elderly. Poisson regressions were used to model CHD and dementia disease rates according to postulated aetiologic mechanisms of AL exposures while controlling for covariates such as age, sex, socioeconomic status and health behaviours.

Results After adjustment for a full range of covariates, we found that those with a higher AL index of 4+ had a 56% increased risk of CHD (Incidence Rate Ratio (IRR) 1.56 (95% Confidence Intervals (CI) 1.08–2.24), with a significant trend p=0.01), whereas the results for dementia were inconclusive (IRR=1.16 (95% CI) 0.68–1.97)).

Conclusion Our results showed that a high physiological burden was related to subsequent CHD, supporting the hypothesis that a cumulative index of ‘biological dysregulation’ could act as an early determinant of CHD. However, although higher levels of cortisol and increased risk for dementia, this multisystem etiological model of allostasis was not predictive of dementia in this particular study.