The mismatch negativity as an index of cognitive abilities in adults with Down syndrome.

Down syndrome (DS) is associated with an ultra-high risk of developing Alzheimer's disease (AD). Understanding variability in pre-AD cognitive abilities may help understand cognitive decline in this population. The mismatch negativity (MMN) is an event-related potential component reflecting the detection of deviant stimuli that is thought to represent underlying memory processes, with reduced MMN amplitudes being associated with cognitive decline. To further understand the MMN in adults with DS without AD, we explored the relationships between MMN, age, and cognitive abilities (memory, language, and attention) in 27 individuals (aged 17-51) using a passive auditory oddball task. Statistically significant MMN was present only in 18 individuals up to 41 years of age and the latency were longer than canonical parameters reported in the literature. Reduced MMN amplitude was associated with lower memory scores, while longer MMN latencies were associated with poorer memory, verbal abilities, and attention. Therefore, the MMN may represent a valuable index of cognitive abilities in DS. In combination with previous findings, we hypothesize that while MMN response and amplitude may be associated with AD-related memory loss, MMN latency may be associated with speech signal processing. Future studies may explore the potential impact of AD on MMN in people with DS.

Dietary Vitamin K1 intake is associated with lower long-term fracture-related hospitalization risk: the Perth longitudinal study of ageing women.

This study examined the association between dietary Vitamin K1 intake with fracture-related hospitalizations over 14.5 years in community-dwelling older Australian women (n = 1373, ≥70 years). Dietary Vitamin K1 intake at baseline (1998) was estimated using a validated food frequency questionnaire and a new Australian Vitamin K nutrient database, which was supplemented with published data. Over 14.5 years, any fracture (n = 404, 28.3%) and hip fracture (n = 153, 10.7%) related hospitalizations were captured using linked health data. Plasma Vitamin D status (25OHD) and the ratio of undercarboxylated osteocalcin (ucOC) to total osteocalcin (tOC) from serum was assessed at baseline. Estimates of dietary Vitamin K1 intake were supported by a significant inverse association with ucOC : tOC; a marker of Vitamin K status (r = -0.12, p < 0.001). Compared to women with the lowest Vitamin K1 intake (Quartile 1, <61 µg d-1), women with the highest Vitamin K1 intake (Quartile 4, ≥99 µg d-1) had lower hazards for any fracture- (HR 0.69 95%CI 0.52-0.91, p < 0.001) and hip fracture-related hospitalization (HR 0.51 95%CI 0.32-0.79, p < 0.001), independent of 25OHD levels, as part of multivariable-adjusted analysis. Spline analysis suggested a nadir in the relative hazard for any fracture-related hospitalizations at a Vitamin K1 intake of approximately 100 µg day-1. For hip fractures, a similar relationship was apparent. Higher dietary Vitamin K1 is associated with lower long-term risk for any fracture- and hip fracture-related hospitalizations in community-dwelling older women.

Oxidative stress and memory decline in adults with Down syndrome: longitudinal study.

By the age of 40, virtually all patients with Down syndrome (DS) have neuropathological changes characteristic of Alzheimer's disease (AD). The aim of our study was to investigate whether the levels of superoxide dismutase enzymes (SOD), glutathione peroxidase (GPx), or their ratio could predict cognitive decline in people with DS over a 4-year period. Thirty-two adults with DS participated in a longitudinal study with SOD and GPx assays at baseline. Informants rated their functional ability and memory function at baseline and at 4 years follow-up. The more able adults with DS also completed assessments of language skills and memory, at two different time points 4 years apart. Twenty-six individuals with DS completed assessments of memory (Modified Memory Object Task, MOMT), adaptive behavior (ABAS), and receptive vocabulary (British Picture vocabulary, BPVS) at both time-points. SOD positively correlated with change on the MOMT score (r = 0.578, p = 0.015). There were no significant correlations between GPx level or SOD/GPx ratio and temporal changes in ABAS, BPVS, or MOMT scores. Our results suggest that SOD predicts memory decline over time and that these antioxidant enzymes could be a potential target for prevention of memory deterioration in adults with DS. Further research is required to test whether supplements which improve SOD function can also prevent cognitive decline. These findings may also have implications for prevention of cognitive decline in other groups which are at high risk of developing dementia, such as adults with familial AD or mild cognitive impairment.

Oxidative stress and cognitive ability in adults with Down syndrome.

AIMS: We aimed to study the hypothesis that high levels of superoxide dismutase (SOD1), previously reported in Down syndrome, would be associated with poorer ability on cognitive tests. Compensatory rises in the activity of glutathione peroxidase (GPx) was expected to be associated with better ability, so that a high ratio between SOD1 and GPx was hypothesised to be the best predictor of poorer cognitive performance. METHODS: 32 adults with Down syndrome between the ages of 18 and 45 years donated blood samples for SOD1 and GPx assays and urine for Isoprostane 8,12-iso-iPF(2alpha)-VI assay, a specific biomarker of lipid peroxidation in vivo. Informants rated functional ability and memory function for all participants, and those adults with DS that was able to, also completed psychometric assessments of language ability and memory. RESULTS: Neither SOD1 nor GPx were related to the elevated markers of lipid peroxidation previously described in living adults with DS, and our hypothesis that an increased SOD1/GPx ratio would be correlated with worse performance on cognitive or functional measures was not supported. Contrary to our hypothesis, we found that low SOD1/GPx ratios were associated with worse memory ability, which remained after controlling for confounders such as sex, age or nutritional supplements. CONCLUSIONS: The anti-oxidant system in DS is implicated in the cognitive phenotype associated with the chromosomal disorder, but the variations in the phenotype could result from several possible gene or gene product interactions. Much further research is required before it will be possible to counteract the oxidative stress associated with DS.