ABSTRACT
Age-related brain iron accumulation is linked with oxidative stress, neurodegeneration and cognitive decline. Certain nutrients can reduce brain iron concentration in animal models, however, this association is not well established in humans. Moreover, it remains unknown if nutrition can moderate the effects of age on brain iron concentration and/or cognition. Here, we explored these issues in a sample of 73 healthy older adults (61-86 years old), while controlling for several factors such as age, gender, years of education, physical fitness and alcohol-intake. Quantitative susceptibility mapping was used for assessment of brain iron concentration and participants performed an N-Back paradigm to evaluate working memory performance. Nutritional-intake was assessed via a validated questionnaire. Nutrients were grouped into nutrition factors based on previous literature and factor analysis. One factor, comprised of vitamin E, lysine, DHA omega-3 and LA omega-6 PUFA, representing food groups such as nuts, healthy oils and fish, moderated the effects of age on both brain iron concentration and working memory performance, suggesting that these nutrients may slow the rate of brain iron accumulation and working memory declines in aging.
Subject(s)
Aging/metabolism , Brain/metabolism , Brain/physiology , Diet, Healthy , Eating/physiology , Iron/metabolism , Memory, Short-Term/physiology , Aged , Aged, 80 and over , Cognitive Dysfunction/etiology , Female , Humans , Male , Middle Aged , Nerve Degeneration/etiology , Oxidative Stress , Surveys and QuestionnairesABSTRACT
INTRODUCTION: We tested if water exchange across the blood-brain barrier (BBB), estimated with a noninvasive magnetic resonance imaging (MRI) technique, is associated with cerebrospinal fluid (CSF) biomarkers of Alzheimer's disease (AD) and neuropsychological function. METHODS: Forty cognitively normal older adults (67-86 years old) were scanned with diffusion-prepared, arterial spin labeling (DP-ASL), which estimates water exchange rate across the BBB (kw ). Participants also underwent CSF draw and neuropsychological testing. Multiple linear regression models were run with kw as a predictor of CSF concentrations and neuropsychological scores. RESULTS: In multiple brain regions, BBB kw was positively associated with CSF amyloid beta (Aß)42 concentration levels. BBB kw was only moderately associated with neuropsychological performance. DISCUSSION: Our results suggest that low water exchange rate across the BBB is associated with low CSF Aß42 concentration. These findings suggest that kw may be a promising noninvasive indicator of BBB Aß clearance functions, a possibility which should be further tested in future research.
Subject(s)
Amyloid beta-Peptides , Blood-Brain Barrier/metabolism , Healthy Volunteers , Magnetic Resonance Imaging , Peptide Fragments , Water/metabolism , Aged , Alzheimer Disease/metabolism , Alzheimer Disease/pathology , Amyloid beta-Peptides/cerebrospinal fluid , Amyloid beta-Peptides/metabolism , Biomarkers/cerebrospinal fluid , Brain/pathology , Female , Humans , Male , Peptide Fragments/cerebrospinal fluid , Peptide Fragments/metabolism , Spin Labels , tau Proteins/cerebrospinal fluidABSTRACT
Excessive brain iron negatively affects working memory and related processes but the impact of cortical iron on task-relevant, cortical brain networks is unknown. We hypothesized that high cortical iron concentration may disrupt functional circuitry within cortical networks supporting working memory performance. Fifty-five healthy older adults completed an N-Back working memory paradigm while functional magnetic resonance imaging (fMRI) was performed. Participants also underwent quantitative susceptibility mapping (QSM) imaging for assessment of non-heme brain iron concentration. Additionally, pseudo continuous arterial spin labeling scans were obtained to control for potential contributions of cerebral blood volume and structural brain images were used to control for contributions of brain volume. Task performance was positively correlated with strength of task-based functional connectivity (tFC) between brain regions of the frontoparietal working memory network. However, higher cortical iron concentration was associated with lower tFC within this frontoparietal network and with poorer working memory performance after controlling for both cerebral blood flow and brain volume. Our results suggest that high cortical iron concentration disrupts communication within frontoparietal networks supporting working memory and is associated with reduced working memory performance in older adults.
