Association of early-onset Type 2 diabetes with cognitive impairment is partially mediated by increased pulse pressure

Aims: Type 2 diabetes mellitus (T2DM) has been shown to be associated with cognitive decline and dementia. As earlier onset of diabetes implies a longer disease duration and an increased risk to complications, we sought to investigate the effect of T2DM onset on cognitive function of our patients.

Methods: We administered the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) to T2DM patients aged 45-85 from our SMART2D cohort. We assessed the association of the T2DM onset age (both continuous and stratified into 3 groups: early-onset ≤40 (n = 326), middle-aged onset 41-64 (n = 703) and late-onset ≥65 years old (n = 38)) and RBANS cognitive indices in 1067 patients. Potential mediation of this association by vascular compliance using mediation analysis was investigated.

Results: T2DM onset associates significantly with RBANS total score. Patients with early T2DM onset have lower RBANS total score as compared to patients with middle-aged onset (β = -2.01, p = 0.0102) and those with late-onset (β = -5.80, p = 0.005). This association was partially mediated by pulse pressure index (25.8%), with indirect effect of 0.028 (Bootstrapped-CI: 0.008-0.047).

Conclusions: Association of early-onset T2DM with cognitive impairment is partly mediated by diminished vascular compliance. Appropriate screening and assessment of cognitive function is important for early intervention and management of cognitive impairment.