Association and Causal Relationship of Midlife Obesity and Related Metabolic Disorders with Old Age Cognition

Abstract

Epidemiological studies suggest a relationship between midlife metabolism and old age cognition. We examined the effect of midlife BMI and related metabolic conditions on old age cognitive performance and whether there was evidence from direct causal pathways behind these associations in a large sample of Finnish twins. Midlife variables of 2606 twin individuals were based on postal questionnaires and registry records. Old age cognitive status was measured by using a validated telephone interview. Midlife BMI, cardiovascular disease, hypertension and diabetes were each associated with old age cognition when adjusted for sex, education, birth year and age at the interview. Similarly, overweight increased the risk for categories of mild impairment of cognitive function and likely dementia. Cardiovascular disease diminished the mean cognitive score also among discordant twin pairs (β-estimate=1.10, p-value= 0.012). Weight gain more than 1.7 kg/m(2) and loss more than 2 kg/m(2) within an average of 5.6 years were associated with lower cognitive performance independently of BMI. An additive genetic correlation explained the association between BMI and old age cognition (r(A)=-0.12, 95% CI -0.21; -0.03), but adjustment for education led to loss of significance (r(A)=-0.06, 95% CI -0.16; 0.03). Midlife metabolic diseases, especially diabetes, are independently associated with impaired cognition in old age. Even a more subtle weight change than suggested previously was associated with lower old age cognition. There was evidence from direct causal pathway between cardiovascular disease and old age cognition, while the correlation between midlife BMI and old age cognition was explained mostly by genetic factors.