INTRODUCTION

Recently, dynamic contrast enhanced MR techniques have been able to detect very small changes in blood-brain barrier (BBB) integrity.⁴ This has allowed cognitive dysfunction to be associated with BBB disruption in elderly populations.¹ Advancements in MR imaging and improvement in post-processing techniques have provided a non-invasive approach to examine associations between cognition and BBB integrity in humans. Disruption of BBB integrity may be a key mechanism early in cognitive decline.

METHODS

The Adventist Health Study-2 (AHS-2) is a longstanding prospective cohort study of over 96,000 members of the Seventh-Day Adventist Church in the US and Canada. The AHS-2 CAN sub-study examined the relationship between dietary patterns and cognitive function. Here we present data from a sample of 40 AHS-2 CAN participants. Participants were 60-70 years old, had baseline neuropsychological assessment approximately one year prior, did not have dementia, or any other neurological disorder. All participants underwent repeat neurocognitive testing with the same battery of neuropsychological tests used to detect age-related changes in elderly populations. Tests included measures of global cognitive functioning (Mini-Mental State Examination), language (Boston Naming Test, Letter Fluency/FAS and Category Fluency/Animals), and verbal learning and memory (Rey Auditory Verbal Learning Test, 2nd Edition (RAVLT)², Rey Auditory Verbal Learning Test- Total recall trials (RAVLTIR), Rey Auditory Verbal Learning Test- Short-delay recall (RAVLTSD) and Rey Auditory Verbal Learning Test- Long delay recall (RAVLTLD)). Participants had a brain MRI with and without contrast on a 3T (Siemens Medical Systems, Erlangen, Germany) scanner using a 32-channel array head coil. Sequences included 3D T1-weighted MPRAGE, Dynamic Contrast Enhanced (DCE), 30-direction Diffusion Tensor Imaging (DTI) and SWI. DCE was used to evaluate BBB integrity. Data was processed with the software package ROCKETSHIP³ using the Patlak model to calculate K_trans. K_trans values were evaluated in the hippocampus, frontal white matter, corpus callosum, thalamus, caudate nucleus and internal capsule. Statistical analyses were performed using SPSS. Pearson correlation coefficients were calculated for K_trans values in different brain regions and scores on individual cognitive tests.

RESULTS

The mean age of the participants was 76.25 years (SD=8.28, min age=63 years, max=90 years). Participants were well-educated and their estimated VIQ indicated high level of premorbid intelligence. K_trans values were negatively correlated with scores on the RAVLTIR and RAVLSD for all brain regions, but only RAVLTIR reached statistical significance for the thalamus. K_trans values were negatively correlated with category fluency (animals) for all brain regions, however; associations were statistically significant for frontal white matter, thalamus and caudate nucleus.

DISCUSSION

The hippocampus along with the anterior and medial nuclei of the thalamus, the medial and basal parts of the striatum and hypothalamus form the limbic system, which helps coordinate declarative (explicit) memory for recent events. In this study, disruption of BBB integrity estimated by DCE-MRI was associated with worse performance on tests for verbal learning and memory and category fluency.

CONCLUSION

This pilot study supports the need for additional research in which participants are followed with annual neuropsychological assessment and neuroimaging to further understand relationship between cognitive functioning and neuro-biomarkers such as measures of BBB.

Acknowledgements

This study was supported by the GRASP award by Loma Linda University.