Higher Fasting Plasma Glucose is Associated with Increased Cortical Thinning Over 12 Years: The PATH Through Life Study

Marnie E. Shaw, Julia Nettersheim, Perminder S. Sachdev, Kaarin J. Anstey, Nicolas Cherbuin

Recent evidence suggests that type 2 diabetes (T2D) is associated with accelerated brain ageing, consistent with the observation of increased risk of cognitive impairment and dementia in affected individuals. Even non-diabetic individuals with impaired fasting plasma glucose (IFG) levels have shown increased cerebral atrophy, compared to individuals with normal glucose levels. We tested whether longitudinal rates of age-related cortical thinning were associated with fasting plasma glucose levels in a large sample (n = 322) of early-old age individuals (60-66 years) who were scanned with magnetic resonance imaging (1.5 T) on up to four occasions over 12 years. Higher plasma glucose levels (measured on up to three occasions) were associated with increased cortical thinning in individuals with T2D as well as those with IFG, with a similar trend for individuals with normal fasting glucose (NFG) levels. Across groups, a 1 mmol/l increase in plasma glucose (above 5 mmol/l in NFG and IFG and above 6.1 mmol/l in T2D) resulted in a 10-13% increase in annual cortical thinning. Increased cortical thinning was detected in insular cortex, as well as posterior cingulate, parahippocampus and medial orbitofrontal cortex. Our results provide support for the idea that raised plasma glucose levels, even in the normal range, are associated with accelerated age-related cortical atrophy.