BackgroundExcessive exposure to manganese (Mn), an essential trace element, has been shown to be neurotoxic, especially when inhaled. Few studies have examined potential effects of Mn on cognitive functions of environmentally exposed children.ObjectiveThis study was intended to estimate environmental exposure to Mn resulting from mining and processing and to explore its association with intellectual function of school-age children.MethodsChildren between 7 and 11 years of age from the Molango mining district in central Mexico (n = 79) and communities with similar socioeconomic conditions that were outside the mining district (n = 93) participated in the cross-sectional evaluation. The revised version of the Wechsler Intelligence Scale for Children adapted for the Mexican population was applied. Concentrations of Mn in blood (MnB) and hair (MnH) were used as biomarkers of exposure.ResultsExposed children had significantly higher median values for MnH (12.6 μg/g) and MnB (9.5 μg/L) than did nonexposed children (0.6 μg/g and 8.0 μg/L, respectively). MnH was inversely associated with Verbal IQ [β = −0.29; 95% confidence interval (CI), −0.51 to −0.08], Performance IQ (β = −0.08; 95% CI, −0.32 to 0.16), and Total Scale IQ (β = −0.20; 95% CI, −0.42 to 0.02). MnB was inversely but nonsignificantly associated with Total and Verbal IQ score. Age and sex significantly modified associations of MnH, with the strongest inverse associations in young girls and little evidence of associations in boys at any age. Associations with MnB did not appear to be modified by sex but appeared to be limited to younger study participants.ConclusionsThe findings from this study suggest that airborne Mn environmental exposure is inversely associated with intellectual function in young school-age children.

Our data indicate that Abeta(42) is elevated in plasma in familial Alzheimer disease (FAD) mutation carriers (MCs) and suggests that this level may decrease with disease progression prior to the development of overt dementia. We also demonstrated that the ratio of Abeta(42) to Abeta(40) was reduced in the CSF of nondemented MCs and that elevations of t-tau and p-tau(181) are sensitive indicators of presymptomatic disease. Our finding of elevated F(2)-isoprostane levels in the CSF of preclinical FAD MCs suggests that oxidative stress occurs downstream to mismetabolism of amyloid precursor protein.

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Background Mutations in the presenilin (PSEN1, PSEN2) and amyloid precursor protein (APP) genes cause familial Alzheimer’s disease (FAD) in a nearly fully penetrant, autosomal dominant manner, providing a unique opportunity to study presymptomatic individuals who can be predicted to develop Alzheimer’s disease (AD) with essentially 100% certainty. Using tensor-based morphometry (TBM), we examined brain volume differences between presymptomatic and symptomatic FAD mutation carriers and non-carrier (NC) relatives. Methods Twenty-five mutation carriers and 10 NC relatives underwent brain MRI and clinical assessment. Four mutation carriers had dementia (MUT-Dem), 12 had amnestic mild cognitive impairment (MUT-aMCI) and nine were cognitively normal (MUT-Norm). TBM brain volume maps of MUT-Norm, MUT-aMCI and MUT-Dem subjects were compared to NC subjects. Results MUT-Norm subjects exhibited significantly smaller volumes in the thalamus, caudate and putamen. MUT-aMCI subjects had smaller volumes in the thalamus, splenium and pons, but not in the caudate or putamen. MUT-Dem subjects demonstrated smaller volumes in temporal, parietal and left frontal regions. As non-demented carriers approached the expected age of dementia diagnosis, this was associated with larger ventricular and caudate volumes and a trend towards smaller temporal lobe volume. Conclusions Cognitively intact FAD mutation carriers had lower thalamic, caudate and putamen volumes, and we found preliminary evidence for increasing caudate size during the predementia stage. These regions may be affected earliest during prodromal stages of FAD, while cortical atrophy may occur in later stages, when carriers show cognitive deficits. Further studies of this population will help us understand the progression of neurobiological changes in AD.

Persons at-risk for autosomal dominant neurodegenerative diseases provide the opportunity to efficiently test preventive interventions. Only a minority of such persons, however, choose to undergo revealing genetic testing, presenting a challenge to enrollment. Thirty-four preclinical Latinos (n = 26) and non-Latinos at-risk for familial Alzheimer’s disease (FAD) unaware of their genetic status were administered a questionnaire exploring their interest in undergoing revealing genetic testing at baseline and in the context of eligibility for four prevention trials of increasing invasiveness. Forty-four percent of subjects expressed a baseline interest in undergoing revealing testing which increased to 85% in order to be eligible for a study of an oral drug "felt to be very safe.” If there were a 50% chance of receiving placebo, this number dropped to 62% (p = 0.02). For those not interested in a study involving a 50% chance of receiving placebo, a range of 5% to 40% chance of receiving placebo was given as acceptable. For more invasive studies, living in the U.S. (as opposed to Mexico) positively influenced the likelihood of participating. Our data suggests that clinical trial designs in which persons must confront their genetic status prior to enrollment are feasible. Study designs to minimize the likelihood of being placed on placebo or provide the eventual administration of the drug through open-label extensions should be considered.