APOE ε4 alters associations between docosahexaenoic acid and preclinical markers of Alzheimer's disease.

Docosahexaenoic acid is the main long-chain omega-3 polyunsaturated fatty acids in the brain and accounts for 30-40% of fatty acids in the grey matter of the human cortex. Although the influence of docosahexaenoic acid on memory function is widely researched, its association with brain volumes is under investigated and its association with spatial navigation is virtually unknown. This is despite the fact that spatial navigation deficits are a new cognitive fingerprint for symptomatic and asymptomatic Alzheimer's disease. We investigated the cross-sectional relationship between docosahexaenoic acid levels and the major structural and cognitive markers of preclinical Alzheimer's disease, namely hippocampal volume, entorhinal volume and spatial navigation ability. Fifty-three cognitively normal adults underwent volumetric magnetic resonance imaging, measurements of serum docosahexaenoic acid (DHA, including lysophosphatidylcholine DHA) and APOE ε4 genotyping. Relative regional brain volumes were calculated and linear regression models were fitted to examine DHA associations with brain volume. APOE genotype modulated serum DHA associations with entorhinal cortex volume and hippocampal volume. Linear models showed that greater serum DHA was associated with increased entorhinal cortex volume, but not hippocampal volume, in non APOΕ Îµ4 carriers. APOE also interacted with serum lysophosphatidylcholine DHA to predict hippocampal volume. After testing interactions between DHA and APOE on brain volume, we investigated whether DHA and APOE interact to predict spatial navigation performance on a novel virtual reality diagnostic test for Alzheimer's disease in an independent population of APOE genotyped adults (n = 46). APOE genotype modulated DHA associations with spatial navigation performance, showing that DHA was inversely associated with path integration in APOE ε4 carriers only. This exploratory analysis suggests that interventions aiming to increase DHA blood levels to protect against cognitive decline should consider APOE ε4 carrier status. Future work should focus on replicating our initial findings and establishing whether a specific dose of supplementary DHA, at a particular time in the preclinical disease course can have a positive impact on Alzheimer's disease progression in APOE ε4 carriers.

Multiple-day high-dose beetroot juice supplementation does not improve pulmonary or muscle deoxygenation kinetics of well-trained cyclists in normoxia and hypoxia.

Dietary nitrate (NO3-) supplementation via beetroot juice (BR) has been reported to lower oxygen cost (i.e., increased exercise efficiency) and speed up oxygen uptake (VO2) kinetics in untrained and moderately trained individuals, particularly during conditions of low oxygen availability (i.e., hypoxia). However, the effects of multiple-day, high dose (12.4 mmol NO3- per day) BR supplementation on exercise efficiency and VO2 kinetics during normoxia and hypoxia in well-trained individuals are not resolved. In a double-blinded, randomized crossover study, 12 well-trained cyclists (66.4 ± 5.3 ml min-1∙kg-1) completed three transitions from rest to moderate-intensity (~70% of gas exchange threshold) cycling in hypoxia and normoxia with supplementation of BR or nitrate-depleted BR as placebo. Continuous measures of VO2 and muscle (vastus lateralis) deoxygenation (ΔHHb, using near-infrared spectroscopy) were acquired during all transitions. Kinetics of VO2 and deoxygenation (ΔHHb) were modeled using mono-exponential functions. Our results showed that BR supplementation did not alter the primary time constant for VO2 or ΔHHb during the transition from rest to moderate-intensity cycling. While BR supplementation lowered the amplitude of the VO2 response (2.1%, p = 0.038), BR did not alter steady state VO2 derived from the fit (p = 0.258), raw VO2 data (p = 0.231), moderate intensity exercise efficiency (p = 0.333) nor steady state ΔHHb (p = 0.224). Altogether, these results demonstrate that multiple-day, high-dose BR supplementation does not alter exercise efficiency or oxygen uptake kinetics during normoxia and hypoxia in well-trained athletes.

Impaired microvascular reactivity after eccentric muscle contractions is not restored by acute ingestion of antioxidants or dietary nitrate.

Unaccustomed eccentric exercise leads to impaired microvascular function but the underlying mechanism is unknown. In this study, we evaluated the role of oxidative stress and of nitric oxide (NO) bioavailability. Thirty young men and women performed eccentric contractions of the tibialis anterior (TA) muscle (ECC), with the contralateral leg serving as nonexercising control (CON). Participants were randomized into three groups ingesting an antioxidant cocktail (AO), beetroot juice (BR) or placebo 46 h postexercise. At baseline and 48 h postexercise, hyperemic responses to brief muscle contractions and 5 min of cuff occlusion were assessed bilaterally in the TA muscles using blood oxygen level dependent (BOLD) magnetic resonance imaging. Eccentric contractions resulted in delayed time-to-peak (~22%; P < 0.001), blunted peak (~21%; P < 0.001) and prolonged time-to-half relaxation (~12%, P < 0.001) in the BOLD response to brief contractions, with no effects of AO or BR, and no changes in CON. Postocclusive time-to-peak was also delayed (~54%; P < 0.001) in ECC, with no effects of AO or BR, and no changes in CON. Impaired microvascular reactivity after eccentric contractions is confined to the exercised tissue, and is not restored with acute ingestion of AO or BR. Impairments in microvascular reactivity after unaccustomed eccentric contractions may result from structural changes within the microvasculature that can diminish muscle blood flow regulation during intermittent activities requiring prompt adjustments in oxygen delivery.

Chronic high-dose beetroot juice supplementation improves time trial performance of well-trained cyclists in normoxia and hypoxia.

Dietary nitrate (NO3-) supplementation via beetroot juice (BR) is known to improve endurance performance in untrained and moderately trained individuals. However, conflicting results exist in well-trained individuals. Evidence suggests that the effects of NO3- are augmented during conditions of reduced oxygen availability (e.g., hypoxia), thereby increasing the probability of performance improvements for well-trained athletes in hypoxia vs. normoxia. This randomized, double-blinded, counterbalanced-crossover study examined the effects of 7 days of BR supplementation with 12.4 mmol NO3- per day on 10-km cycling time trial (TT) performance in 12 well-trained cyclists in normoxia (N) and normobaric hypoxia (H). Linear mixed models for repeated measures revealed increases in plasma NO3- and NO2- after supplementation with BR (both p < 0.001). Further, TT performance increased with BR supplementation (∼1.6%, p < 0.05), with no difference between normoxia and hypoxia (p = 0.92). For respiratory variables there were significant effects of supplementation on VO2 (p < 0.05) and VE (p < 0.05) such that average VO2 and VE during the TT increased with BR, with no difference between normoxia and hypoxia (p ≥ 0.86). We found no effect of supplementation on heart rate, oxygen saturation or muscle oxygenation during the TT. Our results provide new evidence that chronic high-dose NO3- supplementation improves cycling performance of well-trained cyclists in both normoxia and hypoxia.

System-Specific Patterns of Thalamocortical Connectivity in Early Brain Development as Revealed by Structural and Functional MRI.

The normal development of thalamocortical connections plays a critical role in shaping brain connectivity in the prenatal and postnatal periods. Recent studies using advanced magnetic resonance imaging (MRI) techniques in neonates and infants have shown that abnormal thalamocortical connectivity is associated with adverse neurodevelopmental outcomes. However, all these studies have focused on a single neuroimaging modality, overlooking the dynamic relationship between structure and function at this early stage. Here, we study the relationship between structural and functional thalamocortical connectivity patterns derived from healthy full-term infants scanned with diffusion-weighted MRI and resting-state functional MRI within the first weeks of life (mean gestational age = 39.3 ± 1.2 weeks; age at scan = 24.2 ± 7.9 days). Our results show that while there is, in general, good spatial agreement between both MRI modalities, there are regional variations that are system-specific: regions involving primary-sensory cortices exhibit greater structural/functional overlap, whereas higher-order association areas such as temporal and posterior parietal cortices show divergence in spatial patterns of each modality. This variability illustrates the complementarity of both modalities and highlights the importance of multimodal approaches.