Endocrine Abstracts

Background: Metabolic disorders such as type 2 diabetes are risk factors for the development of dementia. In addition to vascular dysfunction, insulin resistance may be important since altered insulin sensitivity is associated with changes in neurogenesis. Polycystic ovary syndrome (PCOS) is a disorder characterised by insulin resistance. Little is known about the impact of metabolic abnormalities on brain structure and function in younger adults.

Objective: To examine whether PCOS is associated with microstructural abnormalities and to relate these to cognitive functioning.

Methods: women with PCOS (age 31±6 years, BMI 30±6 kg/m²) and 19 control subjects (age 31±7 years, BMI 29±6 kg/m²) underwent diffusion tensor MRI and detailed cognitive assessment. Diffusion tensor imaging measures, including fractional anisotropy (FA) and mean diffusivity (MD) were compared between groups and related to cognitive performance. We analysed FA, MD and axial diffusivity (AD) values by using a tract based spatial statistics (TBSS) technique (whole brain analysis). Tractography was also performed to reconstruct individual temporal lobe white matter tracts.

Results: Subjects with PCOS had higher testosterone (1.56±0.6 (PCOS), 0.9±0.6 nmol/l (controls); P=0.01) and insulin response to glucose challenge (IAUC 93 151±42 694 (PCOS), 61 933±29 614 (controls); P=0.04). Despite similar educational achievement (NART IQ 122, P=0.35) subjects with PCOS performed less well on a summary measure of cognitive performance (principal components analysis, t=2.9, P=0.007). TBSS showed areas of decreased AD in PCOS throughout the white matter skeleton. The genu of the corpus callosum and right cingulum also showed decreased MD and altered tissue volume fraction in PCOS (P<0.05).

Conclusions: Subjects with PCOS performed less well than controls in a measure of executive function and episodic memory. This is not attributable to BMI or premorbid intelligence. Our data suggest that alterations in brain structure, and subtle deficits in cognition, emerge at a young age in insulin-resistant subjects.