Mild exercise in female subjects impairs complex learning independent of hydration status and emotion.

INTRODUCTION: Depending on type, intensity and duration, exercise can have both beneficial and detrimental effects on cognitive function. The impact of exercise on learning and memory is also sensitive to hydration status, so we hypothesized that mild hypohydration induced with exercise, will adversely impact executive and complex memory function tasks and that these changes in cognitive function are independent of changes in emotion. METHODS: Using a cross over design, on separate days 11 women exercised on a recumbent bicycle. On day 1, women exercised to 1.5% hypohydration at 34°C, and <10% rh, on day 2, water loss from sweating was replaced by drinking water (euhydration). Pre- and post-euhydration and hypohydration, subjects underwent computer based cognitive tasks (simple, learning, memory, executive function) and visual analog testing to determine emotion. RESULTS: Exercise increased Groton Maze Learning Test errors within both conditions: [Pre: 41.5±11.8, Post: 46.8±12.4, and Pre: 41.9±9.2, Post: 46.5±12.9, hypohydrated and euhydrated, respectively, Pre vs Post, ANOVA, time effect, P=0.007], a test of acquisition, storage, and use of new knowledge. None of the measures of emotion were affected by exercise under either hydration condition. CONCLUSIONS: A bout of mild aerobic exercise compromised performance on a complex learning and memory task, but this change was unaffected by hydration status or emotion.

Cognitive ability in Down syndrome and its relationship to urinary neopterin, a marker of activated cellular immunity.

BACKGROUND: Neopterin is an unconjugated pteridine that is secreted in large quantities by activated macrophages and can be used as a clinical marker of activated cellular immunity and oxidative stress. We aimed to investigate whether urinary neopterin levels are associated with cognitive function in people with Down syndrome (DS). METHODS: Out of 32 adults with DS who originally participated in a longitudinal study, 25 were followed up at 4 years. Informants rated their adaptive behavior (ABAS) and the adults with DS attempted assessments of language skills and memory at both baseline and follow-up time points (Modified Memory Object Task, MOMT), and receptive vocabulary (British Picture Vocabulary Scale, BPVS). RESULTS: Neopterin/creatinine levels were negatively correlated with change in the MOMT total score (Spearman's Rho=-0.517, p=0.020) and change in the MOMT delayed recall score (Spearman's Rho=-0.577, p=0.008) over time, i.e. higher neopterin/creatinine level was associated with worse performance on a test of cognitive ability over time. CONCLUSION: Urine neopterin may have potential as a biomarker for memory decline in Down syndrome, and could potentially also help to track progression of mild cognitive impairment (MCI) to Alzheimer's disease in other high risk populations.

Memory decline in Down syndrome and its relationship to iPF2alpha, a urinary marker of oxidative stress.

BACKGROUND: Lipid peroxidation may be a marker of free-radical-mediated injury associated with Alzheimer's disease (AD). We aimed to investigate whether changes in lipid peroxidation is associated with cognitive decline in individuals with Down syndrome over a 4-year period. METHODS: Thirty-two adults with DS participated in a longitudinal study with urinary isoprostane 8,12-iso-iPF2alpha (iPF2alpha) assays at baseline and four years follow-up. Informants rated their functional ability and memory function and the adults with DS attempted assessments of language skills and memory. Twenty-six individuals completed assessments of memory (Modified Memory Object Task, MOMT), adaptive behavior (ABAS), and receptive vocabulary (British Picture vocabulary, BPVS) at both time-points. RESULTS: Overall change in iPF2alpha level was negatively correlated with change in the MOMT score (Spearman's Rho =  -0.576, p = 0.006), i.e., increased lipid peroxidation was correlated with worse memory functioning over time. An increase of ≥ 0.02 ng/mg creatinine iPF2α had good sensitivity (85.7%), positive predictive value (75%,), specificity (85.7%) and negative predictive value (92.3%) for memory decline. CONCLUSION: Change in iPF2alpha over time may have potential as a biomarker for memory decline in Down syndrome and potentially also help to track progression of MCI to AD in the general population.

Improving memory and decreasing cognitive impairment in Tg-APPswe/PSEN1dE9 mice with Aß3-10 repeat fragment plasmid by reducing Aß deposition and inflammatory response.

The present study aimed to investigate the effects of Aß3-10 repeat fragment plasmid for the treatment of Tg-APPswe/PSEN1dE9 (Tg) mice. The plasmid pcDNA3.1-(Aß3-10)10-CpG was constructed and intramuscularly injected into 12-month-old Tg mice. Through the use of behavioral tests, anti-Aß antibody and Aß assays, cytokine assay, Aß deposition, and astrocytes analysis results demonstrated that Aß3-10 repeat fragment plasmid exhibited immunogenicity and reduced memory impairment in Tg mice via clearance of cerebral Aß deposition, without significant side effects. Aß3-10 repeat fragment plasmid immunization reduced Th1 cell-mediated immunity, secretion of interferon-γ, and stimulation to astrocytes. These data showed that the Aß3-10 repeat fragment plasmid improved memory and decreased cognitive impairment in Tg mice by reducing Aß deposition and inflammatory responses.

Improved cognitive-cerebral function in older adults with chromium supplementation.

Insulin resistance is implicated in the pathophysiological changes associated with Alzheimer's disease, and pharmaceutical treatments that overcome insulin resistance improve memory function in subjects with mild cognitive impairment (MCI) and early Alzheimer's disease. Chromium (Cr) supplementation improves glucose disposal in patients with insulin resistance and diabetes. We sought to assess whether supplementation with Cr might improve memory and neural function in older adults with cognitive decline. In a placebo-controlled, double-blind trial, we randomly assigned 26 older adults to receive either chromium picolinate (CrPic) or placebo for 12 weeks. Memory and depression were assessed prior to treatment initiation and during the final week of treatment. We also performed functional magnetic resonance imaging (fMRI) scans on a subset of subjects. Although learning rate and retention were not enhanced by CrPic supplementation, we observed reduced semantic interference on learning, recall, and recognition memory tasks. In addition, fMRI indicated comparatively increased activation for the CrPic subjects in right thalamic, right temporal, right posterior parietal, and bifrontal regions. These findings suggest that supplementation with CrPic can enhance cognitive inhibitory control and cerebral function in older adults at risk for neurodegeneration.

Selective enhancement of spatial learning under chronic psychosocial stress.

The hippocampus has long been proved to be implicated in several learning and memory processes. Being integrated into the limbic-hypothalamus-pituitary-adrenal axis, the hippocampus also plays an active role in the regulation of the stress response. Long lasting elevated levels of glucocorticoids resulting from a prolonged stress exposure affect hippocampal functions and structure, inducing learning and memory alterations and suppressing cell proliferation in the adult dentate gyrus. Here, adult male tree shrews (Tupaia belangeri) exposed to chronic psychosocial stress were tested repeatedly on a holeboard apparatus using two different learning tasks devised to evaluate hippocampal-dependent and hippocampal-independent cognitive function. We show that chronic stress enhanced learning in animals performing the hippocampal-dependent task, whereas no stress-induced effect was found in the hippocampal-independent task. Additionally, after five weeks of stress, cell proliferation was reduced in the hippocampal dentate gyrus. These results indicate that specific memory processes not only may remain intact, but indeed are facilitated by chronic stress, despite elevated cortisol levels and suppressed hippocampal cell proliferation.