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The longitudinal relationship between anterior cingulate glutathione and executive functioning in individuals at risk for dementia: a magnetic resonance spectroscopy study
Abstract   Peer reviewed

The longitudinal relationship between anterior cingulate glutathione and executive functioning in individuals at risk for dementia: a magnetic resonance spectroscopy study

Shantel L Duffey, Jim Lagopoulos, Nathan Cross, Haley LaMonica, Loren Mowszowski, Simon J G Lewis, Ian B Hickie and Sharon L Naismith
Alzheimer's & Dementia, Vol.13(7, Supplement), p.P1383
Alzheimer's Association International Conference, 2017 (London, United Kingdom, 15-Jul-2017–20-Jul-2017)
2017
DOI: https://doi.org/10.1016/j.jalz.2017.06.2131
url
https://doi.org/10.1016/j.jalz.2017.06.2131View
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Abstract

Neurosciences Clinical Sciences
Background: Oxidative stress is characterised by an imbalance in the redox state of cells, either via the overproduction of reactive oxygen species or antioxidant system dysfunction. Our prior work has shown, using proton magnetic resonance spectroscopy (1H-MRS), that glutathione (GSH), the brain's major antioxidant and a marker of oxidative stress, is associated with executive functioning in the anterior cingulate cortex (ACC). This study aims to follow individuals longitudinally to determine the relationship between change in GSH concentration and executive functioning in individuals 'at risk' for dementia. Methods: Data collection is ongoing for this study and full results will be available for presentation in mid-2017. However, data to-date has been collected on 15 individuals 'at risk' for dementia, that is, presenting with subjective cognitive complaints and/or mild cognitive impairment. All participants were recruited from the Healthy Brain Ageing Clinic at University of Sydney, and underwent comprehensive psychiatric, medical, neuropsychological assessment and an MRI scan where 1H-MRS data in the ACC was obtained. GSH data was reported as a ratio to creatine (Cr) to facilitate comparison between subjects and across time points. Executive functioning was assessed via the Trail Making Test-Part B (TMT-B; expressed as an age-adjusted z-score). Individuals were invited to return to the clinic for a repeat of all baseline measures after >12 months. Results: Of the data currently available, the mean time between baseline and follow-up assessment was 3.5 years (SD=1.2 years) and mean age at baseline assessment was 64.6 years (SD=9.6 years). Overall, change in GSH/Cr correlated significantly with change in performance on the TMT-B (r=0.58, p=0.024). Conclusions: This study will be the largest to examine the longitudinal relationship between oxidative stress status and cognitive functioning in a cohort 'at-risk' for dementia. Preliminary outcomes show that an increase in GSH is associated with improved executive functioning over a 3.5 year period. This data has important implications for the prevention of cognitive decline and dementia, with intervention studies aimed at supporting antioxidant defenses and optimizing the redox state of cells now warranted.

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