Insulin resistance is associated with reductions in specific cognitive domains and increases in CSF tau in cognitively normal adults

Simon M Laws, Scott Gaskin, Amy Woodfield, Velandai Srikanth, David Bruce, Paul E. Fraser, Tenielle Porter, Philip Newsholme, Nadeeja Wijesekara, Samantha Burnham, Vincent Doré, Qiao-Xin Li, Paul Maruff, Colin Louis Masters, Stephanie Rainey-Smith, Christopher Rowe, Olivier Salvado, Victor L Villemagne, Ralph N Martins, Giuseppe Verdile

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22 Citations (Scopus)

Abstract

Growing evidence supports the hypothesis that type 2 diabetes (T2D) increases the risk of developing dementia. Experimental evidence from mouse models demonstrates that the induction of T2D/insulin resistance (IR) can promote the accumulation of Alzheimer's disease (AD) pathological features. However, the association of T2D with pathological and clinical phenotypes in humans is unclear. Here we investigate the relationship of indices of IR (HOMA-IR) and pancreatic β-cell function (HOMA-B) with cognitive performance across several domains (Verbal/Visual Episodic Memory, Executive Function, Language and a measure of Global cognition) and AD biomarkers (CSF Aβ42, T-tau/P-tau, hippocampal volume and neocortical Aβ-amyloid burden). We reveal that HOMA-IR (p < 0.001) incrementally increases across diagnostic groups, becoming significantly elevated in the AD group compared with cognitively normal (CN) adults. In CN adults, higher HOMA-IR was associated with poorer performance on measures of verbal episodic memory (p = 0.010), executive function (p = 0.046) and global cognition (p = 0.007), as well as with higher CSF T-tau (p = 0.008) and P-tau (p = 0.014) levels. No association was observed with CSF Aβ or imaging modalities. Together our data suggest that IR may contribute to reduced cognitive performance and the accumulation of CSF tau biomarkers in cognitively normal adults.

Original languageEnglish
Article number9766
Number of pages11
JournalScientific Reports
Volume7
Issue number1
DOIs
Publication statusPublished - 1 Dec 2017

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