Document Type

Journal Article


Nature Publishing Group

Place of Publication

United Kingdom


School of Medical and Health Sciences / Centre of Excellence for Alzheimer’s Disease Research and Care




Commonwealth Scientific Industrial and research Organization (CSIRO

Edith Cowan University (ECU)

Mental Health Research institute (MHRI)

National Ageing Research Institute (NARI)

Austin Health

CogState Ltd.

National Health and Medical Research Council (NHMRC)

Dementia Collaborative Research Centres program (DCRC2)

Science and Industry Endowment Fund (SIEF)

Cooperative Research Centre (CRC) for Mental Health – funded through the CRC Program (Grant ID:20100104)

Australian Government Initiative

GV was supported by the Curtin Senior Resarch Fellowship (CRF140196)

West Australian Department of Health Merit Award

National Health and Medical Research Council

Grant Number

NHMRC Number : APP1105698


Laws, S. M., Gaskin, S., Woodfield, A., Srikanth, V., Bruce, D., Fraser, P. E., ... & Doré, V. (2017). Insulin resistance is associated with reductions in specific cognitive domains and increases in CSF tau in cognitively normal adults. Scientific Reports, 7(1).


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.



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This work is licensed under a Creative Commons Attribution 4.0 License.

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