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Results 1-5 (5)
 

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1.  Disclosure of APOE Genotype for Risk of Alzheimer's Disease 
The New England journal of medicine  2009;361(3):245-254.
Background
The apolipoprotein E (APOE) genotype provides information on the risk of Alzheimer's disease, but the genotyping of patients and their family members has been discouraged. We examined the effect of genotype disclosure in a prospective, randomized, controlled trial.
Methods
We randomly assigned 162 asymptomatic adults who had a parent with Alzheimer's disease to receive the results of their own APOE genotyping (disclosure group) or not to receive such results (nondisclosure group). We measured symptoms of anxiety, depression, and test-related distress 6 weeks, 6 months, and 1 year after disclosure or nondisclosure.
Results
There were no significant differences between the two groups in changes in time-averaged measures of anxiety (4.5 in the disclosure group and 4.4 in the nondisclosure group, P = 0.84), depression (8.8 and 8.7, respectively; P = 0.98), or test-related distress (6.9 and 7.5, respectively; P=0.61). Secondary comparisons between the non-disclosure group and a disclosure subgroup of subjects carrying the APOE ε4 allele (which is associated with increased risk) also revealed no significant differences. However, the ε4-negative subgroup had a significantly lower level of test-related distress than did the ε4-positive subgroup (P=0.01). Subjects with clinically meaningful changes in psychological outcomes were distributed evenly among the nondisclosure group and the ε4-positive and ε4-negative subgroups. Baseline scores for anxiety and depression were strongly associated with post-disclosure scores of these measures (P<0.001 for both comparisons).
Conclusions
The disclosure of APOE genotyping results to adult children of patients with Alzheimer's disease did not result in significant short-term psychological risks. Test-related distress was reduced among those who learned that they were APOE ε4–negative. Persons with high levels of emotional distress before undergoing genetic testing were more likely to have emotional difficulties after disclosure. (ClinicalTrials.gov number, NCT00571025.)
doi:10.1056/NEJMoa0809578
PMCID: PMC2778270  PMID: 19605829
2.  Age-related differences in gap detection: Effects of task difficulty and cognitive ability 
Hearing research  2009;264(1-2):21-29.
Differences in gap detection for younger and older adults have been shown to vary with the complexity of the task or stimuli, but the factors that contribute to these differences remain unknown. To address this question, we examined the extent to which age-related differences in processing speed and workload predicted age-related differences in gap detection. Gap detection thresholds were measured for 10 younger and 11 older adults in two conditions that varied in task complexity but used identical stimuli: (1) gap location fixed at the beginning, middle, or end of a noise burst and (2) gap location varied randomly from trial to trial from the beginning, middle, or end of the noise. We hypothesized that gap location uncertainty would place increased demands on cognitive and attentional resources and result in significantly higher gap detection thresholds for older but not younger adults. Overall, gap detection thresholds were lower for the middle location as compared to beginning and end locations and were lower for the fixed than the random condition. In general, larger age-related differences in gap detection were observed for more challenging conditions. That is, gap detection thresholds for older adults were significantly larger for the random condition than for the fixed condition when the gap was at the beginning and end locations but not the middle. In contrast, gap detection thresholds for younger adults were not significantly different for the random and fixed condition at any location. Subjective ratings of workload indicated that older adults found the gap-detection task more mentally demanding than younger adults. Consistent with these findings, results of the Purdue Pegboard and Connections tests revealed age-related slowing of processing speed. Moreover, age group differences in workload and processing speed predicted gap detection in younger and older adults when gap location varied from trial to trial; these associations were not observed when gap location remained constant across trials. Taken together, these results suggest that age-related differences in complex measures of auditory temporal processing may be explained, in part, by age-related deficits in processing speed and attention.
doi:10.1016/j.heares.2009.09.017
PMCID: PMC2868108  PMID: 19800958
aging; auditory temporal processing; gap detection; processing speed; workload; cognitive
3.  At the Heart of the Ventral Attention System: the Right Anterior Insula 
Human brain mapping  2009;30(8):2530-2541.
The anterior insula has been hypothesized to provide a link between attention-related problem solving and salience systems during the coordination of and evaluation of task performance. Here we test the hypothesis that the anterior insula/medial frontal operculum (aI/fO) provides linkage across systems supporting task demands and attention systems by examining patterns of functional connectivity during word recognition and spatial attention functional imaging tasks. A shared set of frontal regions (right aI/fO, right dorsolateral prefrontal cortex, bilateral anterior cingulate) were engaged, regardless of perceptual domain (auditory or visual) or mode of response (word production or button press). We present novel evidence that: 1) the right aI/fO is functionally connected with other frontal regions implicated in executive function and not just brain regions responsive to stimulus salience; and 2) that the aI/fO, but not the ACC, exhibits significantly correlated activity with other brain regions specifically engaged by tasks with varying perceptual and behavioral demands. These results support the hypothesis that the right aI/fO aids in the coordination and evaluation of task performance across behavioral tasks with varying perceptual and response demands.
doi:10.1002/hbm.20688
PMCID: PMC2712290  PMID: 19072895
4.  Protein Reactivity of 3,4-Dihydroxyphenylacetaldehyde, a Toxic Dopamine Metabolite, is Dependent on both the Aldehyde and Catechol 
Chemical research in toxicology  2009;22(7):1256-1263.
Dopamine (DA) has been implicated as an endogenous neurotoxin to explain the selective neurodegeneration as observed for Parkinson's disease (PD). However, previous work demonstrated 3,4-dihydroxyphenylacetaldehyde (DOPAL) to be more toxic than DA. DOPAL is generated as a part of DA catabolism via the activity of monoamine oxidase and the mechanism of DOPAL toxicity is proposed to involve protein modification. Previous studies have demonstrated protein reactivity via the aldehyde moiety; however, DOPAL contains two reactive functional groups (catechol and aldehyde) both with the potential for protein adduction. The goal of this work was to determine whether protein modification by DOPAL occurs via a thiol-reactive quinone generated from oxidation of the catechol, which is known to occur for DA, or if the aldehyde forms adducts with amine nucleophiles. To accomplish this objective, the reactivity of DOPAL towards N-acetyl-lysine (NAL), N-acetyl-cysteine (NAC) and two model proteins was determined. In addition, several DOPAL analogues were obtained and used for comparison of reactivity. Results demonstrate that at pH 7.4 and 37°C, the order of DOPAL reactivity is NAL ≫ NAC and the product of NAL and DOPAL is stable in the absence of reducing agent. Moreover, DOPAL will react with model proteins, but in the presence of amine-selective modifiers citraconic anhydride and 2-iminothiolane hydrochloride, the reactivity of DOPAL towards the proteins is diminished. In addition, DOPAL-mediated protein cross-linking is observed when a model protein or a protein mixture (i.e. mitochondria lysate) are treated with DOPAL at concentrations of 5-100 μM. Protein cross-linking was diminished in the presence of ascorbate, suggesting the involvement of a quinone in DOPAL-mediated protein modification. These data indicate DOPAL to be highly reactive towards protein nucleophiles with the potential for protein cross-linking.
doi:10.1021/tx9000557
PMCID: PMC2717024  PMID: 19537779
5.  Speech recognition in younger and older adults: a dependency on low-level auditory cortex 
A common complaint of older adults is difficulty understanding speech, especially in challenging listening environments. In addition to well known declines in the peripheral auditory system that reduce audibility, age-related changes in central auditory and attention-related systems are hypothesized to have additive negative effects on speech recognition. We examined the extent to which functional and structural differences in speech- and attention-related cortex predicted differences in word recognition between 18 younger adults (19–39 years) and 18 older adults (61–79 years). Subjects performed a word recognition task in an MRI scanner where the intelligibility of words was parametrically varied. Older adults exhibited significantly poorer word recognition in a challenging listening condition compared to younger adults. An anteromedial Heschl’s gyrus/superior temporal gyrus (HG/STG) region, engaged by the word recognition task, exhibited age group differences in gray matter volume and predicted word recognition in younger and older adults. Age group differences in anterior cingulate (ACC) activation were also observed. The association between HG gray matter volume, word recognition, and ACC activation was present after controlling for hearing loss. In younger and older adults, causal path modeling analyses demonstrated that individual variation in left HG/STG morphology affected word recognition performance, which was reflected by error monitoring activity in the dorsal ACC. These results have clinical implications for rehabilitation and suggest that some of the perceptual difficulties experienced by older adults are due to structural changes in HG/STG. More broadly, the results suggest the possibility that aging may exaggerate developmental limitations on the ability to recognize speech.
doi:10.1523/JNEUROSCI.0412-09.2009
PMCID: PMC2717741  PMID: 19439585
aging; auditory cortex; gray matter; word recognition; auditory; speech

Results 1-5 (5)