Quantitative Assessment of Variation in CT Parameters on Texture Features: Pilot Study Using a Nonanatomic Phantom.

Our aim was to evaluate changes in texture features based on variations in CT parameters on a phantom. Scans were performed with varying milliampere, kilovolt, section thickness, pitch, and acquisition mode. Forty-two texture features were extracted by using an in-house-developed Matlab program. Two-tailed t tests and false-detection analyses were performed with significant differences in texture features based on detector array configurations (Q values = 0.001-0.006), section thickness (Q values = 0.0002-0.001), and acquisition mode (Q values = 0.003-0.006). Variations in milliampere and kilovolt had no significant effect.

Real-life driving outcomes in Parkinson disease.

OBJECTIVE: To determine the incidence of and risk factors for driving outcomes in drivers with Parkinson disease (PD). METHODS: In a prospective cohort study, we ascertained the time until driving cessation, a crash, or a traffic citation using self-report and state Department of Transportation records in 106 licensed, active drivers with PD and 130 controls. RESULTS: Drivers with PD stopped driving earlier than controls, hazard ratio (95% confidence interval) = 7.09 (3.66-13.75), p < 0.001. Cumulative incidence of driving cessation at 2 years after baseline was 17.6% (11.5%-26.5%) for PD and 3.1% (1.2%-8.1%) for controls. No significant differences between groups on times to first crash or citation were detected. However, the number of observed crashes was low. Cox proportional hazards models showed that significant baseline risk factors for driving cessation in PD were older age, preference to be driven by somebody else, positive crash history, use of compensatory strategies, low driving exposure, impairments in visual perception (especially visual processing speed and attention) and cognitive abilities, parkinsonism (especially activities of daily living score and total daily dose of antiparkinsonian medications), and higher error counts on a road test. Within PD, crashes were associated with poorer postural stability and history of driving citations, and citations were associated with younger age and road errors at baseline. CONCLUSIONS: Drivers with PD are at a higher risk of driving cessation than elderly control drivers. A battery evaluating motor and nonmotor aspects of PD, driving record, and performance can be useful in assessing future driving outcomes in PD.

Association between type 1 diabetes and GWAS SNPs in the southeast US Caucasian population.

The present study was conducted to assess genetic associations for type 1 diabetes (T1D) reported in previous genome-wide association studies (GWAS). A total of 21 previously reported single-nucleotide polymorphisms (SNPs) were genotyped by TaqMan assays in 1434 Caucasian T1D patients and 1864 normal controls from Georgia. Analysis of the samples identified 18 SNPs (PTPN22, INS, IFIH1, SH2B3, ERBB3, CTLA4, C14orf181, CTSH, CLEC16A, CD69, ITPR3, C6orf173, SKAP2, PRKCQ, RNLS, IL27, SIRPG and CTRB2) with putative association.

Road safety in drivers with Parkinson disease.

OBJECTIVE: To assess road safety and its predictors in drivers with Parkinson disease (PD). METHODS: Licensed, active drivers with PD (n = 84; age = 67.3 +/- 7.8, median Hoehn & Yahr stage II) and controls (n = 182; age = 67.6 +/- 7.5) underwent cognitive, visual, and motor tests, and drove a standardized route in urban and rural settings in an instrumented vehicle. Safety errors were judged and documented by a driving expert based on video data review. RESULTS: Drivers with PD committed more total safety errors compared to controls (41.6 +/- 14.6 vs 32.9 +/- 12.3, p < 0.0001); 77.4% of drivers with PD committed more errors than the median total error count of the controls (medians: PD = 39.5, controls = 31.0). Lane violations were the most common error category in both groups. Group differences in some error categories became insignificant after results were adjusted for demographics and familiarity with the local driving environment. The PD group performed worse on tests of motor, cognitive, and visual abilities. Within the PD group, older age and worse performances on tests of visual acuity, contrast sensitivity, attention, visuospatial abilities, visual memory, and general cognition predicted error counts. Measures of visual processing speed and attention and far visual acuity were jointly predictive of error counts in a multivariate model. CONCLUSIONS: Overall, drivers with Parkinson disease (PD) had poorer road safety compared to controls, but there was considerable variability among the drivers with PD, and some performed normally. Familiarity with the driving environment was a mitigating factor against unsafe driving in PD. Impairments in visual perception and cognition were associated with road safety errors in drivers with PD.

Incidence of and risk factors for cognitive impairment in an early Parkinson disease clinical trial cohort.

OBJECTIVE: To investigate the incidence of and risk factors for cognitive impairment in a large, well-defined clinical trial cohort of patients with early Parkinson disease (PD). METHODS: The Mini-Mental State Examination (MMSE) was administered periodically over a median follow-up period of 6.5 years to participants in the Deprenyl and Tocopherol Antioxidative Therapy of Parkinsonism trial and its extension studies. Cognitive impairment was defined as scoring 2 standard deviations below age- and education-adjusted MMSE norms. RESULTS: Cumulative incidence of cognitive impairment in the 740 participants with clinically confirmed PD (baseline age 61.0 +/- 9.6 years, Hoehn-Yahr stage 1-2.5) was 2.4% (95% confidence interval: 1.2%-3.5%) at 2 years and 5.8% (3.7%-7.7%) at 5 years. Subjects who developed cognitive impairment (n = 46) showed significant progressive decline on neuropsychological tests measuring verbal learning and memory, visuospatial working memory, visuomotor speed, and attention, while the performance of the nonimpaired subjects (n = 694) stayed stable. Cognitive impairment was associated with older age, hallucinations, male gender, increased symmetry of parkinsonism, increased severity of motor impairment (except for tremor), speech and swallowing impairments, dexterity loss, and presence of gastroenterologic/urologic disorders at baseline. CONCLUSIONS: The relatively low incidence of cognitive impairment in the Deprenyl and Tocopherol Antioxidative Therapy of Parkinsonism study may reflect recruitment bias inherent to clinical trial volunteers (e.g., younger age) or limitations of the Mini-Mental State Examination-based criterion. Besides confirming known risk factors for cognitive impairment, we identified potentially novel predictors such as bulbar dysfunction and gastroenterologic/urologic disorders (suggestive of autonomic dysfunction) early in the course of the disease.

Driving under low-contrast visibility conditions in Parkinson disease.

OBJECTIVE: To assess driving performance in Parkinson disease (PD) under low-contrast visibility conditions. METHODS: Licensed, active drivers with mild to moderate PD (n = 67, aged 66.2 +/- 9.0 years, median Hoehn-Yahr stage = 2) and controls (n = 51, aged 64.0 +/- 7.2 years) drove in a driving simulator under high- (clear sky) and low-contrast visibility (fog) conditions, leading up to an intersection where an incurring vehicle posed a crash risk in fog. RESULTS: Drivers with PD had higher SD of lateral position (SDLP) and lane violation counts (LVC) than controls during fog (p < 0.001). Transition from high- to low-contrast visibility condition increased SDLP and LVC more in PD than in controls (p < 0.01). A larger proportion of drivers with PD crashed at the intersection in fog (76.1% vs 37.3%, p < 0.0001). The time to first reaction in response to incursion was longer in drivers with PD compared with controls (median 2.5 vs 2.0 seconds, p < 0.0001). Within the PD group, the strongest predictors of poor driving outcomes under low-contrast visibility conditions were worse scores on measures of visual processing speed and attention, motion perception, contrast sensitivity, visuospatial construction, motor speed, and activities of daily living score. CONCLUSIONS: During driving simulation under low-contrast visibility conditions, drivers with Parkinson disease (PD) had poorer vehicle control and were at higher risk for crashes, which were primarily predicted by decreased visual perception and cognition; motor dysfunction also contributed. Our results suggest that drivers with PD may be at risk for unsafe driving in low-contrast visibility conditions such as during fog or twilight.

Predictors of driving safety in early Alzheimer disease.

OBJECTIVE: To measure the association of cognition, visual perception, and motor function with driving safety in Alzheimer disease (AD). METHODS: Forty drivers with probable early AD (mean Mini-Mental State Examination score 26.5) and 115 elderly drivers without neurologic disease underwent a battery of cognitive, visual, and motor tests, and drove a standardized 35-mile route in urban and rural settings in an instrumented vehicle. A composite cognitive score (COGSTAT) was calculated for each subject based on eight neuropsychological tests. Driving safety errors were noted and classified by a driving expert based on video review. RESULTS: Drivers with AD committed an average of 42.0 safety errors/drive (SD = 12.8), compared to an average of 33.2 (SD = 12.2) for drivers without AD (p < 0.0001); the most common errors were lane violations. Increased age was predictive of errors, with a mean of 2.3 more errors per drive observed for each 5-year age increment. After adjustment for age and gender, COGSTAT was a significant predictor of safety errors in subjects with AD, with a 4.1 increase in safety errors observed for a 1 SD decrease in cognitive function. Significant increases in safety errors were also found in subjects with AD with poorer scores on Benton Visual Retention Test, Complex Figure Test-Copy, Trail Making Subtest-A, and the Functional Reach Test. CONCLUSION: Drivers with Alzheimer disease (AD) exhibit a range of performance on tests of cognition, vision, and motor skills. Since these tests provide additional predictive value of driving performance beyond diagnosis alone, clinicians may use these tests to help predict whether a patient with AD can safely operate a motor vehicle.

Amnesia and driving.

Two experienced drivers who developed severe amnesia due to bilateral hippocampal lesions participated in a series of standardized challenges of driving performance and knowledge of driving rules. During drives in a high fidelity simulator and on the road in an instrumented vehicle, they demonstrated vehicle control similar to that of normal drivers on measures of steering, speed control, safety errors, and driving with distraction. Their knowledge of driving rules, safety procedures, and road sign meaning also was normal. However, both participants were impaired at following route directions, and both had unsafe responses in a difficult crash avoidance scenario on the simulator. These findings suggest that memory impairment acquired by experienced drivers does not impair most aspects of driving performance, but may increase safety risk under some challenging circumstances.

Driving with distraction in Parkinson disease.

OBJECTIVE: To assess the effects of auditory-verbal distraction on driving performance in Parkinson disease (PD). METHODS: We tested licensed, currently active drivers with mild-to-moderate PD (n = 71) and elderly controls with no neurologic disease (n = 147) on a battery of cognitive, visual, and motor tests. While they drove on a four-lane interstate freeway in an instrumented vehicle, we determined at-fault safety errors and vehicle control measures during a distracter task (Paced Auditory Serial Addition Task [PASAT]) and on an uneventful baseline segment. RESULTS: Compared with controls, drivers with PD committed more errors during both baseline and distraction, and drove slower with higher speed variability during distraction. Although the average effect of distraction on driving performance compared with baseline was not different between the groups, the drivers with PD showed a more heterogeneous response to distraction (p < 0.001): the error count increased in 28.2% of drivers with PD (vs 15.8% in controls), decreased in 16.9% (vs 3.4%), and remained stable in 54.9% (vs 80.8%). The odds of increase in safety errors due to distraction was higher in the PD group even after adjusting for baseline errors, level of engagement in PASAT, sex, and education (odds ratio [95% CI] = 2.62 [1.19 to 5.74], p = 0.016). Decreased performance on tests of cognitive flexibility, verbal memory, postural control, and increased daytime sleepiness predicted worsening of driving performance due to distraction within the PD group. CONCLUSION: The quantitative effect of an auditory-verbal distracter task on driving performance was not significantly different between Parkinson disease (PD) and control groups. However, a significantly larger subset of drivers with PD had worsening of their driving safety errors during distraction. Measures of cognition, motor function, and sleepiness predicted effects of distraction on driving performance within the PD group.

Visual dysfunction in Parkinson disease without dementia.

OBJECTIVE: To determine the profiles of visual dysfunction and their relationship to motor and cognitive dysfunction and to disability in mild to moderate Parkinson disease (PD) without dementia. METHODS: Seventy-six independently living participants with mild to moderate PD and 161 neurologically normal older adults were studied using a comprehensive battery to assess visual acuity, contrast sensitivity (CS), visual speed of processing and attention, spatial and motion perception, visual and verbal memory, visuoconstructional abilities, executive functions, depression, and motor function. RESULTS: Participants with PD scored significantly worse on all tests of vision and cognition compared with normal elderly persons. Reduced CS contributed to deficits on tests of spatial and motion perception and attention in participants with PD. Impairments in visual attention and spatial perception predicted worse cognitive function. Worse performances on tests of visual speed of processing and attention, spatial and motion perception, visual construction, and executive functions correlated with measures of postural instability and gait difficulty (in the Motor section of the Unified Parkinson's Disease Rating Scale). Impairments in motor function, visual memory, mood, and executive functions predicted worse disability as measured by Schwab-England Activities of Daily Living Scale. CONCLUSIONS: Patients with mild to moderate Parkinson disease showed impaired visual perception and cognition compared with elderly control subjects. Visual dysfunction contributes to parkinsonian disability through its influences on cognition and locomotion.

Driver landmark and traffic sign identification in early Alzheimer's disease.

OBJECTIVE: To assess visual search and recognition of roadside targets and safety errors during a landmark and traffic sign identification task in drivers with Alzheimer's disease. METHODS: 33 drivers with probable Alzheimer's disease of mild severity and 137 neurologically normal older adults underwent a battery of visual and cognitive tests and were asked to report detection of specific landmarks and traffic signs along a segment of an experimental drive. RESULTS: The drivers with mild Alzheimer's disease identified significantly fewer landmarks and traffic signs and made more at-fault safety errors during the task than control subjects. Roadside target identification performance and safety errors were predicted by scores on standardised tests of visual and cognitive function. CONCLUSIONS: Drivers with Alzheimer's disease are impaired in a task of visual search and recognition of roadside targets; the demands of these targets on visual perception, attention, executive functions, and memory probably increase the cognitive load, worsening driving safety.

Driver route-following and safety errors in early Alzheimer disease.

OBJECTIVE: To assess navigation and safety errors during a route-following task in drivers with Alzheimer disease (AD). DESIGN/METHODS: Thirty-two subjects with probable AD (by National Institute of Neurological and Communicative Disorders criteria) of mild severity and 136 neurologically normal older adults were tested on a battery of visual and cognitive tests of abilities that are critical to safe automobile driving. Each driver also performed a route-finding task administered on the road in an instrumented vehicle. Main outcome variables were number of 1) incorrect turns; 2) times lost; and 3) at-fault safety errors. RESULTS: The drivers with mild AD made significantly more incorrect turns, got lost more often, and made more at-fault safety errors than control subjects, although their basic vehicular control abilities were normal. The navigational and safety errors were predicted using scores on standardized tests sensitive to visual and cognitive decline in early AD. CONCLUSIONS: Drivers with Alzheimer disease made more errors than neurologically normal drivers on a route-following task that placed demands on driver memory, attention, and perception. The demands of following route directions probably increased the cognitive load during driving, which might explain the higher number of safety errors.

Incidence of nondextrality in the NAS/NRC Twin Registry.

Genetic theories still flounder on the fact that similarity of hand preference is the same in monozygotic (MZ) and dizygotic (DZ) twins. Lateral preference on a well-designed set of 5 activities was obtained from 2,131 male pairs. On item analysis, only "throw" discriminated zygosity, attributable to "excess" nondextral MZ pairs. This item is remarkably free of the intense cultural bias against sinistrality.

Pathological laughter and crying: a link to the cerebellum.

Patients with pathological laughter and crying (PLC) are subject to relatively uncontrollable episodes of laughter, crying or both. The episodes occur either without an apparent triggering stimulus or following a stimulus that would not have led the subject to laugh or cry prior to the onset of the condition. PLC is a disorder of emotional expression rather than a primary disturbance of feelings, and is thus distinct from mood disorders in which laughter and crying are associated with feelings of happiness or sadness. The traditional and currently accepted view is that PLC is due to the damage of pathways that arise in the motor areas of the cerebral cortex and descend to the brainstem to inhibit a putative centre for laughter and crying. In that view, the lesions 'disinhibit' or 'release' the laughter and crying centre. The neuroanatomical findings in a recently studied patient with PLC, along with new knowledge on the neurobiology of emotion and feeling, gave us an opportunity to revisit the traditional view and propose an alternative. Here we suggest that the critical PLC lesions occur in the cerebro-ponto-cerebellar pathways and that, as a consequence, the cerebellar structures that automatically adjust the execution of laughter or crying to the cognitive and situational context of a potential stimulus, operate on the basis of incomplete information about that context, resulting in inadequate and even chaotic behaviour.

Decision-making deficits, linked to a dysfunctional ventromedial prefrontal cortex, revealed in alcohol and stimulant abusers.

A decision-making instrument known as the "gambling task" was used, which has been shown to be sensitive to the decision-making impairment of patients with bilateral lesions of the ventromedial prefrontal cortex (VM). Three groups of subjects were tested, substance dependent individuals (SD) (n=41), normal controls (n=40), and VM patients (n=5). All SD met the DSM-IV criteria for dependence, with either alcohol or stimulants (metamphetamine or cocaine) as the primary substance of choice. The results revealed a significant impairment in the performance of SD relative to normal controls. A significantly high proportion of SD (61 vs. only 32.5% of normal controls) performed within the range of the VM patients, while the rest performed within the range of normal controls. General demographic factors such as age, sex, and level of education could not explain these differences in performance. As well, differences in performance were not explained by intelligence (IQ), memory, or performance on standard executive function/frontal lobe tests. Performance on the gambling task was best predicted by a combination of factors, including duration of abstinence, years of abuse, relapses and times in treatment, and the ability to hold gainful employment. The results support the hypothesis that impairment in decision-making linked to a dysfunctional VM cortex is associated with at least a sub-group of SD.

A small-molecule nitroimidazopyran drug candidate for the treatment of tuberculosis.

Mycobacterium tuberculosis, which causes tuberculosis, is the greatest single infectious cause of mortality worldwide, killing roughly two million people annually. Estimates indicate that one-third of the world population is infected with latent M. tuberculosis. The synergy between tuberculosis and the AIDS epidemic, and the surge of multidrug-resistant clinical isolates of M. tuberculosis have reaffirmed tuberculosis as a primary public health threat. However, new antitubercular drugs with new mechanisms of action have not been developed in over thirty years. Here we report a series of compounds containing a nitroimidazopyran nucleus that possess antitubercular activity. After activation by a mechanism dependent on M. tuberculosis F420 cofactor, nitroimidazopyrans inhibited the synthesis of protein and cell wall lipid. In contrast to current antitubercular drugs, nitroimidazopyrans exhibited bactericidal activity against both replicating and static M. tuberculosis. Lead compound PA-824 showed potent bactericidal activity against multidrugresistant M. tuberculosis and promising oral activity in animal infection models. We conclude that nitroimidazopyrans offer the practical qualities of a small molecule with the potential for the treatment of tuberculosis.

Vision and cognition in Alzheimer's disease.

Alzheimer's disease (AD) is known to affect visual pathways, but potential concomitant effects on vision and cognitive performance are not well understood. We studied 43 individuals with AD of mild severity and 22 individuals without dementia on a battery of tests designed to measure multiple aspects of basic and higher-order visual perception and cognition. All subjects performed on the same visual and cognitive test batteries. The results showed no differences between groups on tests of static visual acuity, stereoacuity, dynamic visual acuity or motion direction discrimination. However, individuals with AD performed significantly worse on tests of static spatial contrast sensitivity, visual attention, shape-from-motion, color, visuospatial construction and visual memory. Correlation analyses showed strong relationships between visual and cognitive scores. The findings show that AD affects several aspects of vision and are compatible with the hypothesis that visual dysfunction in AD may contribute to performance decrements in other cognitive domains. The pattern of involvement indicates that AD affects multiple visual neural pathways and regions. It is possible that better understanding of vision-related dysfunction could aid diagnosis and interventions to improve functional capacity in patients with dementia.

Visual attention impairments in Alzheimer's disease.

BACKGROUND: Impaired attention can hinder information processing at multiple levels and may explain aspects of functional decline in aging and dementia. Impairments of attention in early AD may contribute to performance reductions in other cognitive domains, including memory and executive functions. METHOD: - The authors analyzed the scores on a battery of tests of attention and cognitive abilities in 64 older individuals: 42 with mild AD and 22 control subjects without dementia. The authors tested the hypotheses that patients with AD would have impairments of visual attention, and that these impairments would correlate with dysfunction in other key cognitive domains. RESULTS: Patients with AD performed significantly worse than control subjects on measures of sustained attention, divided attention, selective attention, and visual processing speed. The differences were not due to differences in age, education, or basic visual function. Strong relationships were identified between reduced attention skills and overall cognitive impairment. CONCLUSIONS: Deterioration of attention abilities occurs in early stages of AD, and likely contributes to functional decline in these patients. More routine assessment of visual attention deficits could give a more accurate measure of functionally useful perception in patients with AD who show normal visual acuity and visual fields, perhaps providing useful clues to diagnosis and staging.

Long-term sequelae of prefrontal cortex damage acquired in early childhood.

Frontal lobe dysfunction is often invoked as a contributing factor in developmental disorders characterized by chronic maladaptive behavior, but interpretation of relevant neuropsychological findings has been hampered by the limited information available regarding the consequences of focal prefrontal damage early in life. We describe here the long-term behavioral and cognitive sequelae of damage to prefrontal cortex in two young adult patients who had sustained their brain damage prior to 16 months of age. In the context of normal neurological examinations, both cases had remarkable histories of impaired decision making, behavioral dyscontrol, social defects, and abnormal emotion. Performances were primarily normal on a broad range of neuropsychological measures (intellect, memory, language, academic achievement, visual perception, and visuoconstruction), but selective impairments of executive function were evident. Early dysfunction in the prefrontal region may result in severe and chronic social maladjustment despite largely normal cognitive abilities. These findings can help inform neuropsychological evaluation of patients with possible prefrontal dysfunction in the setting of developmental disabilities or early brain trauma.