Effects of mixed metal exposures on MRI diffusion features in the medial temporal lobe.

Background: Environmental exposure to metal mixtures is common and may be associated with increased risk for neurodegenerative disorders including Alzheimer's disease. Objective: This study examined associations of mixed metal exposures with medial temporal lobe (MTL) MRI structural metrics and neuropsychological performance. Methods: Metal exposure history, whole blood metal, and neuropsychological tests were obtained from subjects with/without a history of mixed metal exposure from welding fumes (42 exposed subjects; 31 controls). MTL structures (hippocampus, entorhinal and parahippocampal cortices) were assessed by morphologic (volume, cortical thickness) and diffusion tensor imaging [mean (MD), axial (AD), radial diffusivity (RD), and fractional anisotropy (FA)] metrics. In exposed subjects, correlation, multiple linear, Bayesian kernel machine regression, and mediation analyses were employed to examine effects of single- or mixed-metal predictor(s) and their interactions on MTL structural and neuropsychological metrics; and on the path from metal exposure to neuropsychological consequences. Results: Compared to controls, exposed subjects had higher blood Cu, Fe, K, Mn, Pb, Se, and Zn levels (p's<0.026) and poorer performance in processing/psychomotor speed, executive, and visuospatial domains (p's<0.046). Exposed subjects displayed higher MD, AD, and RD in all MTL ROIs (p's<0.040) and lower FA in entorhinal and parahippocampal cortices (p's<0.033), but not morphological differences. Long-term mixed-metal exposure history indirectly predicted lower processing speed performance via lower parahippocampal FA (p=0.023). Higher whole blood Mn and Cu predicted higher entorhinal diffusivity (p's<0.043) and lower Delayed Story Recall performance (p=0.007) without overall metal mixture or interaction effects. Discussion: Mixed metal exposure predicted MTL structural and neuropsychological features that are similar to Alzheimer's disease at-risk populations. These data warrant follow-up as they may illuminate the path for environmental exposure to Alzheimer's disease-related health outcomes.

Higher hippocampal diffusivity values in welders are associated with greater R2* in the red nucleus and lower psychomotor performance.

INTRODUCTION: Chronic excessive welding exposure may be related to higher metal accumulation and structural differences in different subcortical structures. We examined how welding affected brain structures and their associations with metal exposure and neurobehavioral consequences. METHODS: Study includes 42 welders and 31 controls without a welding history. Welding-related structural differences were assessed by volume and diffusion tensor imaging (DTI) metrics in basal ganglia, red nucleus (RN), and hippocampus. Metal exposure was estimated by both exposure questionnaires and whole blood metal levels. Brain metal accumulations were estimated by R1 (for Mn) and R2* (for Fe). Neurobehavioral status was assessed by standard neuropsychological tests. RESULTS: Compared to controls, welders displayed higher hippocampal mean (MD), axial (AD), and radial diffusivity (RD) (p's < 0.036), but similar DTI or volume in other ROIs (p's > 0.117). Welders had higher blood metal levels (p's < 0.004), higher caudate and RN R2* (p's < 0.014), and lower performance on processing/psychomotor speed, executive function, and visuospatial processing tasks (p's < 0.046). Higher caudate and RN R2* were associated with higher blood Fe and Pb (p's < 0.043), respectively. RN R2* was a significant predictor of all hippocampal diffusivity metrics (p's < 0.006). Higher hippocampal MD and RD values were associated with lower Trail Making Test-A scores (p's < 0.025). A mediation analysis of both groups revealed blood Pb indirectly affected hippocampal diffusivity via RN R2* (p's < 0.041). DISCUSSION: Welding-related higher hippocampal diffusivity metrics may be associated with higher RN R2* and lower psychomotor speed performance. Future studies are warranted to test the role of Pb exposure in these findings.

Higher R2* in the Red Nucleus Is Associated With Lead Exposure in an Asymptomatic Welder Cohort.

Lead is a nonessential metal and may be a coexposure in welding fumes. Preclinical data indicate lead may affect iron regulation. The current study investigated blood lead concentrations and their association with brain iron accumulation in workers with chronic welding fume exposure, with a focus on iron-rich subcortical regions of the cerebellum and basal ganglia. Occupational exposure, whole blood metal, and brain MRI data were obtained from 29 controls and 42 welders. R2* (1/T2*) and R1 (T1 relaxation rate) values were used to estimate brain iron and manganese content, respectively. Blood metals and brain R2* (in the red nucleus [RN], dentate nucleus, caudate, putamen, globus pallidus, and substantia nigra) were compared between groups. Associations between brain R2* values and exposure metrics were tested within each group, and analyses were adjusted for potential confounders. Welders had significantly higher levels of whole blood lead, manganese, iron, and copper. Welders also had higher R2* RN (p = .002), but not R1. A 2nd-order polynomial modeled the association between R2* RN and a long-term welding exposure metric. In welders, but not controls, R2* RN was associated positively with whole blood lead (r = 0.54, p = .003), and negatively with whole blood manganese (r = -0.43, p = .02). Higher blood Pb and lower blood Mn independently accounted for variance in high RN R2*. Together, these data suggest that higher RN R2* values may mark lead exposure in welders. Because lead is a known neurotoxicant, additional studies are warranted to confirm this finding, and ascertain its scientific and public/occupational health implications.

Are foot deformity and plantar sensitivity impairment associated with physical function of community-dwelling older adults?

BACKGROUND: Foot deformities are highly prevalent in older adults and negatively impact their mobility and quality of life. However, the association between foot problems and physical function is still unclear. OBJECTIVE: To investigate whether structural foot deformities and plantar tactile sensitivity are associated with lower extremity physical function impairment in community-dwelling older adults. METHODS: We included 200 men and women aged 60 years and older from a community-based program. The foot assessment included toe deformities and calluses inspection and evaluation of plantar tactile sensitivity using monofilaments. The Short Physical Performance Battery (SPPB) was used to assess lower extremity physical function. We conducted a multivariate logistic regression analysis to investigate the association between foot problems and lower extremity physical function. RESULTS: Hallux valgus was the most prevalent deformity among older adults. Those participants with reduced plantar tactile sensitivity (OR= 2.77; 95% CI: 1.38, 5.55) and a hallux valgus (OR= 2.23; 95% CI: 1.10, 4.52) were more likely to present poor lower extremity physical function. CONCLUSION: Hallux valgus and impaired plantar sensitivity were associated with reduced lower extremity physical function in older adults. Further studies are necessary to identify this causality and to what extent management of these foot problems can improve general mobility and quality of life of older adults.

The walking cane length influences the postural sway of community-dwelling older women.

BACKGROUND: Mobility-related problems in older people may be relieved by the use of walking canes. However, the influence of the cane length on the postural stability of cane users has not been explored. OBJECTIVE: The objective of this study is to examine the influence of a single-point cane with different lengths on the postural sway of regular cane users, older women during two stance positions, with feet parallel and semi-tandem stance. METHODS: Eighteen older women, who used a single-point walking cane for at least 6 months, stood on a force plate with feet parallel or in semitandem position for 40 s. They always used a cane that was adjusted to one of three different lengths resulting from the distance between the wrist crease and the floor, named WF, or this distance plus 7.5 or 10 cm. Amplitude and speed of the centre of pressure (COP) and its components (rambling and trembling) in the anterior-posterior and medial-lateral directions and mean vertical force applied to the cane were compared across cane lengths. RESULTS: The amplitude and velocity of COP, rambling and trembling increased with the cane length. This effect was observed for the anterior-posterior with the feet parallel and in the medial-lateral direction with the semi-tandem position. More force was applied on the shorter cane (WF) in semitandem position. CONCLUSION: Longer canes increased the postural sway in the older women and restricted the body weight loaded on the cane. Improper cane length influences the postural sway particularly in a semitandem stance of regular cane users. This may cause a negative impact on postural stability required in daily life activities. The current findings may contribute to the prescription of this assistive device for older adults.

Combined effects of the light touch and cognitive task affect the components of postural sway.

The light touch (LT) of the fingertip on a rigid surface and the performance of a cognitive task (CT) affect the postural control. The current study examined the mechanisms involved in the control of postural sway (i.e., Rambling and Trembling components of the center of pressure) with the LT and CT performed individually or simultaneously. Thirteen adults stood on a force plate for 70 s while performed the LT, CT (visual searching of specific letters) or both tasks simultaneously. COP, Rambling, and Trembling mean amplitude and speed were computed. COP and Rambling trajectories were highly and Trembling moderately reduced with LT. The CT affected mainly the Rambling component, supporting the role of supraspinal control of postural sway. These findings suggested that while LT influences both supraspinal and peripheral control mechanisms, CT influences mostly the supraspinal mechanisms involved in postural sway. The combined effects of LT and CT improve the postural control with no negative consequences on CT performance.

Effect of force magnitude of touch on the components of postural sway.

BACKGROUND: Lightly touching the tip of the index finger on an external surface reduces the postural sway during upright standing due to the additional somatosensory information provided by the touch to the postural control system. But when the individuals apply more force, it provides more mechanical support. However, because most of the studies investigated only two levels of force, whether the control mechanisms of postural sway are affected by the different force levels was unknown. RESEARCH QUESTION: To examine the influence of the magnitude of force (up to 1, 2, 4, 6 or 8 N) applied to the touch bar on the mechanisms used to control the postural sway during quiet standing with eyes open or closed. METHODS: Ten young right-handed adults stood for 35 s on a force platform, with feet apart, while touched a rigid bar with different force levels with eyes open or closed. The amplitude and velocity of the center of pressure and its components, Rambling and Trembling trajectories, respectively, related to more supraspinal and spinal control mechanisms, were assessed. RESULTS: The touch reduced all trajectories, mainly of the Rambling component and with closed eyes. There was a floor effect of the touch force as amplitudes and velocities were minimal at 4 N of force. SIGNIFICANCE: The component of postural sway under the supraspinal neural control is more affected by different force magnitudes applied to the touch bar.