Evidence of emerging BBB changes in mid-age apolipoprotein E epsilon-4 carriers.

INTRODUCTION: Studies have recognized that the loss of the blood-brain barrier (BBB) integrity is a major structural biomarker where neurodegenerative disease potentially begins. Using a combination of high-quality neuroimaging techniques, we investigated potential subtle differences in BBB permeability in mid-age healthy people, comparing carriers of the apolipoprotein E epsilon-4 (APOEε4) genotype, the biggest risk factor for late onset, non-familial AD (LOAD) with APOEε3 carriers, the population norm. METHODS: Forty-one cognitively healthy mid-age participants (42-59) were genotyped and pseudo-randomly selected to participate in the study by a third party. Blind to genotype, all participants had a structural brain scan acquisition including gadolinium-based dynamic contrast-enhanced magnetic resonance imaging acquired using a T1-weighted 3D vibe sequence. A B1 map and T1 map were acquired as part of the multi-parametric mapping acquisition. RESULTS: Non-significant, but subtle differences in blood-brain barrier permeability were identified between healthy mid-age APOEε4 and APOEε3 carriers, matched on age, education, and gender. DISCUSSION: This study demonstrated a tendency toward BBB permeability in APOEε4 participants emerging from mid-age, with quantitative differences observable on a number of the measures. While the differences did not reach a statistical significance, the results from this study hint at early changes in ε4 carrier BBB that may help identify at-risk populations and facilitate the development of early interventions to change the trajectory of decline.

Increased intraindividual reaction time variability in persons with neuropsychiatric manifestations of systemic lupus erythematosus.

Systemic Lupus Erythematosus (SLE) can affect multiple organ systems, including the central (CNS) and/or peripheral nervous system. Individuals with nervous system involvement (termed Neuropsychiatric SLE or NPSLE) can present with nonspecific symptoms such as cognitive dysfunction. It is difficult to ascertain whether this is a direct consequence of lupus disease activity on the brain. Intraindividual variability, measured through trial-to-trial reaction time variation, has been proposed as a behavioral marker of CNS integrity. We compared 14 NPSLE, 20 non-NPSLE, and 27 age-matched healthy participants using multiple variability metrics. Variability was increased in NPSLE compared with non-NPSLE participants, and was increased throughout the distribution rather than there being a selective increase in extreme reaction times. Variability metrics were strongly intercorrelated providing convergent evidence that the different metrics are tapping similar processes. The results suggest that there is ongoing disruption to cognitive processing in NPSLE and may indicate small fluctuations in attention.