Does T2D Cause Cognitive Decline Later in Life?

In this study, researchers examined the relationship between type 2 diabetes (T2D) and insulin resistance and diminished cognitive function in older age, and whether this association is causal or if other earlier life factors play a role. The population-based British 1946 cohort was used to collect data on 1,780 patients with metabolic variables including T2D, insulin resistance (HOMA2-IR), and HbA1c. Patients underwent evaluation between ages 60 and 64 years, and were assessed for cognitive state (Addenbrooke’s Cognitive Examination III [ACE-III]) and verbal memory at 69 years. The study authors also gathered data on earlier-life socioeconomic position (SEP), cognition at age 8 years, and educational attainment. T2D polygenic risk scores (PSRs) were determined. The researchers employed a two-step approach to data analysis: first, a PRS approach with multivariable linear regression was implemented to determine whether PRSs and metabolic traits and later-life cognitive state were correlated; second, a path model approach was employed to determine the interrelationships between earlier-life measures mid-life T2D features, and cognitive state at age 69 years. According to the study, “The externally weighted PRS for type 2 diabetes was associated with mid-life metabolic traits (e.g. HOMA2-IR β = 0.08 [95% CI, 0.02, 0.16]), but not with ACE-III (β = 0.04 [−0.02, 0.90]) or other cognitive outcomes.” HOMA2-IR was correlated with eventual ACEI-III, but in path modelling analysis when adjusting for the correlation between childhood SEP and education and HOMA2-IR, no direct effect could be established. The same result was obtained for later-life verbal memory.