Predictive Value of a New Brief Cognitive Test for Long-term Functional Outcome in Acute Traumatic Brain Injury.

OBJECTIVE: To determine how results on the EXAmen Cognitif abrégé en Traumatologie (EXACT), a new test specifically designed to briefly assess global cognitive functioning during the acute phase of traumatic brain injury (TBI), can predict long-term functional outcome compared with length of posttraumatic amnesia (PTA), a well-established predictor. DESIGN: Inception cohort. SETTINGS: Level 1 trauma center. PARTICIPANTS: A total of 90 patients (N=90) hospitalized for a moderate or severe TBI. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Performance on the EXACT in the first 3 months after injury and results on the Disability Rating Scale (DRS) at follow-up 1-2 years later. RESULTS: EXACT scores were all correlated with length of PTA and DRS result. Compared with length of PTA, the EXACT added significantly to the regression and improved prediction of functional outcome. More specifically, a total score ≤80 on the EXACT was associated with a higher rate of long-term disability because of more severe TBI consequences. Behavioral regulation and executive functions were the cognitive domains that showed the most impairment, followed by attention and working memory as well as episodic memory. Except for length of PTA and hospital stay, the DRS score was not correlated with other demographic (age, education) or clinical variables (Glasgow Coma Scale and maximum score on the Therapy Intensity Level Scale). CONCLUSIONS: The EXACT can be administered to most patients early in the acute phase of TBI, and results could be used, along with other predictors such as PTA, to estimate their long-term functional sequelae. The EXACT may be a promising brief cognitive instrument for future studies investigating recovery after TBI.

Mild behavioral impairment is associated with ß-amyloid but not tau or neurodegeneration in cognitively intact elderly individuals.

INTRODUCTION: Mild behavioral impairment (MBI) is characterized by the emergence of neuropsychiatric symptoms in elderly persons. Here, we examine the associations between MBI and Alzheimer's disease (AD) biomarkers in asymptomatic elderly individuals. METHODS: Ninety-six cognitively normal elderly individuals underwent MRI, [18 F]AZD4694 ß-amyloid-PET, and [18 F]MK6240 tau-PET. MBI was assessed using the MBI Checklist (MBI-C). Pearson's correlations and voxel-based regressions were used to evaluate the relationship between MBI-C score and [18 F]AZD4694 retention, [18 F]MK6240 retention, and gray matter (GM) volume. RESULTS: Pearson correlations revealed a positive relationship between MBI-C score and global and striatal [18 F]AZD4694 standardized uptake value ratios (SUVRs). Voxel-based regression analyses revealed a positive correlation between MBI-C score and [18 F]AZD4694 retention. No significant correlations were found between MBI-C score and [18 F]MK6240 retention or GM volume. CONCLUSION: We demonstrate for the first time a link between MBI and early AD pathology in a cognitively intact elderly population, supporting the use of the MBI-C as a metric to enhance clinical trial enrolment.

Changes in water manganese levels and longitudinal assessment of intellectual function in children exposed through drinking water.

BACKGROUND: Manganese is commonly found in water but potential neurotoxic effects from exposure through drinking water are poorly understood. We previously reported a cross-sectional study showing that drinking water Mn concentration was associated with lower IQ in children aged 6 to 13 years. OBJECTIVE: For this follow-up study, we aimed to re-assess the relation between exposure to Mn from drinking water and IQ at adolescence. In addition, we aimed to examine whether changes in drinking water Mn concentration was associated with changes in IQ scores. METHODS: From the 380 children enrolled in the baseline study, 287 participated to this follow-up study conducted in average 4.4 years after. Mn concentration was measured in home tap water and children's hair. The relationships between these Mn exposure indicators and IQ scores (Weschsler Abbreviated Scale of Intelligence) at follow-up were assessed with linear regression analysis, adjusting for potential confounders. Intra-individual differences in IQ scores between the two examinations were compared for children whose Mn concentration in water remained stable between examinations, increased or decreased. RESULTS: The mean age at follow-up was 13.7 years (range, 10.5 to 18.0 years). Geometric mean of Mn concentration in water at follow-up was 14.5µg/L. Higher Mn concentration in water measured at follow-up was associated with lower Performance IQ in girls (ß for a 10-fold increase=-2.8, 95% confidence intervals [CI] -4.8 to -0.8) and higher Performance IQ in boys (ß=3.9, 95% CI 1.4 to 6.4). IQ scores were not significantly associated with Mn concentration in hair, although similar trends as for concentration in water were observed. For children whose Mn concentration in water increased between baseline and follow-up, Performance IQ scores decreased significantly (intra-individual difference, -2.4 points). CONCLUSION: Higher levels of Mn in drinking water were associated with lower Performance IQ in girls, whereas the opposite was observed in boys. These findings suggest long-term exposure to Mn through drinking water is associated differently with cognition in boys and girls.

Mapping the basal ganglia alterations in children chronically exposed to manganese.

Chronic manganese (Mn) exposure is associated with neuromotor and neurocognitive deficits, but the exact mechanism of Mn neurotoxicity is still unclear. With the advent of magnetic resonance imaging (MRI), in-vivo analysis of brain structures has become possible. Among different sub-cortical structures, the basal ganglia (BG) has been investigated as a putative anatomical biomarker in MR-based studies of Mn toxicity. However, previous investigations have yielded inconsistent results in terms of regional MR signal intensity changes. These discrepancies may be due to the subtlety of brain alterations caused by Mn toxicity, coupled to analysis techniques that lack the requisite detection power. Here, based on brain MRI, we apply a 3D surface-based morphometry method on 3 bilateral basal ganglia structures in school-age children chronically exposed to Mn through drinking water to investigate the effect of Mn exposure on brain anatomy. Our method successfully pinpointed significant enlargement of many areas of the basal ganglia structures, preferentially affecting the putamen. Moreover, these areas showed significant correlations with fine motor performance, indicating a possible link between altered basal ganglia neurodevelopment and declined motor performance in high Mn exposed children.

MRI pallidal signal in children exposed to manganese in drinking water.

BACKGROUND: Manganese (Mn) can have neurotoxic effects upon overexposure. We previously reported poorer cognitive and motor development in children exposed to Mn through drinking water, suggesting possible neurotoxic effects from Mn in water. Hyperintensity in the globus pallidus (GP) on T1-weighted magnetic resonance imaging (MRI) indicates excessive brain Mn accumulation. Previous studies have reported GP hyperintensity related to Mn exposure in occupationally exposed individuals. However, no study has used MRI in children exposed to Mn in drinking water and who show no sign of overt intoxication. OBJECTIVE: To examine MRI signal intensity in the GP in children exposed to contrasted levels of Mn in drinking water. METHODS: We enrolled 13 children exposed to low Mn concentration in water and 10 children (ages 9-15 years) with high concentration (median of 1 and 145µg/L, respectively). We calculated three MRI T1 indexes: (i) standard pallidal index (PI) using frontal white matter as reference; (ii) PI using pericranial muscles as reference; and (iii) T1 relaxation time. Each MRI index was compared between exposure groups, and with respect to the estimated Mn intake from water consumption. RESULTS: The standard PI did not differ between Mn-exposure groups. However, children in the group with high water-Mn concentration had significantly lower pericranial muscles PI than those with lower exposure and, accordingly, higher T1 relaxation time. Mn intake from water consumption was not correlated with the standard PI, but was significantly related to the pericranial muscles PI and T1 relaxation time. Motor performance was significantly lower in the high-exposure group. CONCLUSION: We observed lower signal intensity in the GP of children with higher exposure to Mn from drinking water. This result stands in contrast to previous MRI reports showing GP hyperintensity with greater Mn exposure. Differences in exposure pathways are discussed as a potential explanation for this discrepancy.

Sex differences in visual evoked potentials in school-age children: what is the evidence beyond the checkerboard?

Visual evoked potentials (VEPs) are known to be influenced by several biological variables, including sex. In adult populations studies using conventional high-contrast checkerboard have shown that females display larger amplitudes and shorter latencies than males. To date, few studies have been conducted in children; the available data suggests that girls display significantly larger amplitudes than boys but the effect on latency is absent or negligible. We investigated sex-related VEP differences in 149 school-age (11.3 ± 0.6 years) children from Northern Quebec using several VEP protocols: achromatic pattern-reversal VEPs at high (95%) and low contrast (30%, 12% and 4%), as well as motion-onset VEPs and isoluminant pattern-reversal VEPs. Girls showed significantly larger amplitudes in achromatic VEPs for most of the contrast levels as well as in N2 response to motion-onset. No significant difference was found regarding the amplitude of isoluminant VEPs. In addition, girls showed shorter latencies for the achromatic N75 and a trend (p<0.1) for the P100, regardless of the contrast level. Interestingly, this latency effect appeared mostly due to head size, not sex. No differences in latency were found for motion or isoluminant responses. Overall, these findings show that sex-related differences are present in children mostly in VEP amplitude not only for high contrast achromatic pattern-reversal but also for low contrast levels and motion-onset VEPs, suggesting that sex affects VEP responses in a general fashion.