The Immediate Effects of Carbon Composite Ankle Foot Orthoses on Balance and Gait in Individuals with Peripheral Neuropathy: A Pilot Study

Peripheral neuropathy (PN) is a neurological disorder that involves damage or disease of the peripheral nervous system. Diabetes is one of the most common causes on PN, while another large percentage of cases are idiopathic in nature. Individuals with PN often experience a distal to proximal progression of motor and sensory deficits such as loss of proprioception, muscle weakness, and loss of ankle reflexes. Since lower extremity proprioception plays a primary role in postural control, individuals with PN demonstrate difficulty maintaining balance, especially under conditions in which vision or vestibular input are also compromised. Because of these deficits, individuals with PN demonstrate an increased risk of falling. To improve balance in these individuals, literature suggests that providing additional or alternative sensory cues may enhance postural control. One practical strategy for improving sensory input that has been investigated is the use of orthotics or ankle-foot orthoses (AFO) to augment tactile and proprioceptive input to the foot and lower leg. Significant improvements in both sensory organization and postural motor control have been shown to occur with some commonly used AFOs, however, relatively little is known about how the newer generation carbon composite AFO may positively or negatively influence individuals with PN.https://ecommons.udayton.edu/dpt_symposium/1012/thumbnail.jp

Examination of candidate exonic variants for association to Alzheimer disease in the Amish.

Alzheimer disease (AD) is the most common cause of dementia. As with many complex diseases, the identified variants do not explain the total expected genetic risk that is based on heritability estimates for AD. Isolated founder populations, such as the Amish, are advantageous for genetic studies as they overcome heterogeneity limitations associated with complex population studies. We determined that Amish AD cases harbored a significantly higher burden of the known risk alleles compared to Amish cognitively normal controls, but a significantly lower burden when compared to cases from a dataset of unrelated individuals. Whole-exome sequencing of a selected subset of the overall study population was used as a screening tool to identify variants located in the regions of the genome that are most likely to contribute risk. By then genotyping the top candidate variants from the known AD genes and from linkage regions implicated previous studies in the full dataset, new associations could be confirmed. The most significant result (p = 0.0012) was for rs73938538, a synonymous variant in LAMA1 within the previously identified linkage peak on chromosome 18. However, this association is specific to the Amish and did not generalize when tested in a dataset of unrelated individuals. These results suggest that additional risk variation in the Amish remains to be identified and likely resides outside of the classical protein coding gene regions

African ancestry APOE e4 non-carriers with higher educational attainment are resilient to Alzheimer disease pathology-specific blood biomarker pTau181

Cognitive and functional abilities in individuals with Alzheimer disease (AD) pathology (ADP) show greater than expected variability. While most individuals show substantial impairments in these abilities, a considerable number show little or no impairments. Factors contributing to this variability are not well understood. For instance, multiple studies have shown that higher levels of education are associated with reduced cognitive impairments among those with ADP. However, it remains unclear whether higher levels of education are associated with functional impairments among those with ADP. We studied 410 AA individuals with advanced levels of pTau181 (a biomarker for ADP; individuals as those having log 10 (pTau181) level greater than one standard deviation above the mean) to determine whether EA (categorized as low EA for individuals with ≤ 8 years of education and high EA for those with >8 years) promotes functional resilience and whether this effect varies between APOE ε4 carriers and non-carriers. We used the four non-memory components of the Clinical Dementia Rating (CDR) to create a composite score (CDR-FUNC) to evaluate functional difficulties (scored from 0=no impairment to 12=severe). We employed the non-parametric Mann-Whitney U test to assess the relationship between EA and CDR-FUNC in advanced levels of pTau181 individuals. The results showed that EA promotes resilience to functional problems in AA individuals with advanced levels of pTau181, such that individuals with high EA are more likely to have better functional ability compared to those with lower EA (W=730.5, p=0.0007). Additionally, we found that the effect of high EA on functional resilience was stronger in ε4 non-carriers compared to ε4 carriers (W=555.5, p=0.022). This study extends the role of cognitive reserve and EA to functional performance showing that cognitive reserve influences the association between ADP burden and functional difficulties. Interestingly, this protective effect seems less pronounced in carriers of the strong genetic risk allele ε4. The results highlight the intricate interplay of genetic and non-genetic factors in AD progression, suggesting a need for more personalized strategies to manage functional decline in AD

Consequences of a Rare Complement Factor H Variant for Age-Related Macular Degeneration in the Amish

PURPOSE. Genetic variants in the complement factor H gene (CFH) have been consistently implicated in age-related macular degeneration (AMD) risk. However, their functional effects are not fully characterized. We previously identified a rare, AMD-associated variant in CFH (P503A, rs570523689) in 19 Amish individuals, but its functional consequences were not investigated. METHODS. We performed genotyping for CFH P503A in 1326 Amish individuals to identify additional risk allele carriers. We examined differences for age at AMD diagnosis between carriers and noncarriers. In blood samples from risk allele carriers and noncarriers, we quantified (i) CFH RNA expression, (ii) CFH protein expression, and (iii) C -reactive protein (CRP) expression. Potential changes to the CFH protein structure were interrogated computationally with Phyre2 and Chimera software programs. RESULTS. We identified 39 additional carriers from Amish communities in Ohio and Indiana. On average, carriers were younger than noncarriers at AMD diagnosis, but this difference was not significant. CFH transcript and protein levels in blood samples from Amish carriers and noncarriers were also not significantly different. CRP levels were also comparable in plasma samples from carriers and noncarriers. Computational protein modeling showed slight changes in the CFH protein conformation that were predicted to alter interactions between the CFH 503 residue and other neighboring residues. CONCLUSIONS. In total, we have identified 58 risk allele carriers for CFH P503A in the Ohio and Indiana Amish. Although we did not detect significant differences in age at AMD diagnosis or expression levels of CFH in blood samples from carriers and noncarriers, we observed modest structural changes to the CFH protein through in silico modeling. Based on our functional and computational observations, we hypothesize that CFH P503A may affect CFH binding or function rather than expression, which would require additional research to confirm

Details of Risk Loci from Meta-Analysis Used to Calculate Total Genetic Risk Score.

<p>Alleles, MAF, and overall OR are published values. Chr = chromosome. Pos = position in bp. MAF = minor allele frequency. OR = odds ratio. Adapted from Lambert, et al, 2013 [<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0118043#pone.0118043.ref016" target="_blank">16</a>]. Allele frequency was calculated using the 921 Amish samples and the 971 samples from the unrelated dataset that passed QC in the follow-up genotyping phase.</p><p>Details of Risk Loci from Meta-Analysis Used to Calculate Total Genetic Risk Score.</p

Demographics of Amish Samples Used For Follow-up Genotyping.

<p>Percent female, age of exam and onset averages and standard deviations were calculated for the 921 samples which passed QC for follow-up genotyping.</p><p>Demographics of Amish Samples Used For Follow-up Genotyping.</p