Neuroticism as a Predictor of Frailty in Old Age: A Genetically Informative Approach

Abstract

Objective: Neuroticism is associated with poor health outcomes, but its contribution to the accumulation of health deficits in old age, i.e. frailty, is largely unknown. We aimed to explore associations between neuroticism and frailty cross-sectionally and over up to 29 years, and to investigate the contribution of shared genetic influences.Method: Data were derived from the UK Biobank (UKB, n=502,631), the Australian Over 50's Study (AO50, n=3,011) and the Swedish Twin Registry (SALT n=23,744, SATSA n=1,637).Associations between neuroticism and the Frailty Index were investigated using regression analysis cross-sectionally in UKB, AO50 and SATSA, and longitudinally in SALT (25-29y follow-up) and SATSA (6 and 23y follow-up). The co-twin control method was applied to explore the contribution of underlying shared familial factors (SALT, SATSA, AO50). Genome-wide polygenic risk scores for neuroticism in all samples were used to further assess whether common genetic variants associated with neuroticism predict frailty.Results: High neuroticism was consistently associated with greater frailty cross-sectionally

Neuroticism polygenic risk predicts conversion from mild cognitive impairment to Alzheimer's disease by impairing inferior parietal surface area

“…The neuroticism personality showed genetic susceptibility to AD by exacerbating cognitive impairment (Zufferey et al, 2017 ), disturbing emotional fragility (Danielsdottir et al, 2019 ) and sleep difficulties (Stephan et al, 2020 ), which in turn makes people more susceptible to various cardiovascular diseases (Lee et al, 2022 ), all of which are high‐risk factors for AD (Andrews et al, 2021 ; Korologou‐Linden et al, 2019 ; Li et al, 2021 ; Stephan et al, 2018 ). Furthermore, neuroticism is an important risk factor for many psychiatric disorders, such as major depressive disorder and schizophrenia (Brainstorm Consortium et al, 2018 ; Genetics of Personality Consortium et al, 2015 ).…”