Statin Use Impairs Cognition and is Associated with Voxel-wise and Network Based Grey Matter Atrophy: Findings from a Cohort Study
Abstract
Background
Statins are the most prevalent treatment for dyslipidaemia, but cognitive side effects are disputed. This study examines the impact of statins on cognition within a prospective study specifically designed to examine cognitive outcomes and underlying pathobiology.
Objective
To evaluate the association between statin-use on cognitive impairment and voxel-wise and network-based grey matter atrophy.
Design
Cross-sectional cognitive and neuroimaging data obtained from a prospective cohort study.
Setting
Community-based, Southeast Asian cohort.
Participants
Participants(n=1170) from the BIOCIS cohort were classified as Cognitively Normal(CN) or Mild Cognitive Impairment(MCI). Participants were categorized into normal cholesterol no statins(S-C-), normal cholesterol with statins(S+C-), and high cholesterol no statins(S-C+).
Exposures
Neuropsychological test battery, Magnetic Resonance Imaging, Apolipoprotein E4 genotyping
Main Outcome(s) and Measure(s)
Montreal Cognitive Assessment (MoCA) and z-scores across episodic memory, executive function, processing speed, visuospatial, and language domains were employed to evaluate cognitive performance and voxel-based and functional network-based grey matter atrophy.
Results
1170 participants (age=61.6±10.3, 63% female), comprising 558 CN and 612 MCI, were included. Among CN, S+C- performed significantly worse than S-C- on MoCA (Cohen’s đ=-0.386, p=0.014), episodic memory (đ=-0.374, p<0.001), executive function (đ=- 0.367, p<0.001), processing speed (đ=-0.551, p<0.001), language (đ=-0.393, p=0.004). Similar poorer cognitive performance among statin users were observed when comparing S+C- and S-C+. Parallel trends were observed in MCI: MoCA (đ=-0.400, p=0.002), episodic memory (đ=-0.430, p<0.001), executive function (đ=-0.364, p<0.001), processing speed (đ=- 0.354, p=0.004), visuospatial (đ=-0.342, p=0.003), language (đ=-0.507, p<0.001). There was a significant effect of longer statin-use duration associating poorer cognitive performance: episodic memory (β=-0.021, corrected-p=0.011), executive function (β=-0.019, corrected- p=0.005), visuospatial (β=-0.026, corrected-p=0.008), language (β=-0.022, corrected- p=0.008). Widespread grey matter atrophy was observed in S+C- compared to S-C- and S-C+ in CN and MCI participants even with stringent false discovery rate correction (corrected- p<0.05). Regional atrophy in default mode and executive control network regions was observed in MCI statin users (corrected-p<0.05).
Conclusions
Statin use and duration was significantly associated with impairment across cognitive domains in CN and MCI participants. Impairment in cognitive function among statin users was correlated to voxel-based and network-based grey matter atrophy in brain regions crucial for cognition. Prospective longitudinal studies need to confirm the adverse cognitive effects of statins and facilitate appropriate clinical use.
Related articles
Related articles are currently not available for this article.