Ergun Y. Uc

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 Parkinsons 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.

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. AD = Alzheimer disease; AVLT = Auditory Verbal Learning Test; Blocks = Block Design subtest; BVRT = Benton Visual Retention Test; CFT = Complex Figure Test; CI = confidence interval; COWA = Controlled Oral Word Association; CS = contrast sensitivity; FVA = far visual acuity; JLO = Judgment of Line Orientation; MCI = mild cognitive impairment; MMSE = Mini-Mental State Examination; NVA = near visual acuity; SFM = structure from motion; TMT = Trail-Making Test; UFOV = Useful Field of View.

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.

Impaired Visual Search in Drivers with Parkinson's Disease

To assess the ability for visual search and recognition of roadside targets and safety errors during a landmark and traffic sign identification task in drivers with Parkinsons disease (PD).

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.

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 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.

Predictors of weight loss in Parkinson's disease

The objective of this study was to examine the change of body weight (BW) among Parkinsons disease (PD) patients and controls over years and determine the predictors of weight loss among PD patients. Studies on weight loss in PD studies are cross‐sectional, have a short follow‐up, or lack in clinical detail. We examined the percentage of BW change over years among 49 PD patients and 78 controls. The controls were from another study on longitudinal evolution of BW and body composition in the elderly. We determined the BW, Hoehn and Yahr (HY) stage, and dyskinesia status of 49 consecutive nondemented PD patients with symptom duration of 6.1 ± 0.7 years (mean ± SEM) and ascertained their BW at the time of diagnosis and 2.4 ± 0.2 years before the diagnosis from medical records. We collected data again 7.2 ± 0.5 years after the first visit. The PD group lost 7.7% ± 1.5% of BW over the entire symptomatic period (13.1 ± 0.8 years), while the control group lost only 0.2% ± 0.7% of BW over 9.9 ± 0.1 years; weight loss was clinically significant (>5%) in 55.6% of PD patients vs. 20.5% of the controls (both P values < 0.001, adjusted for sex, baseline age, and observation period duration). PD patients lost weight in both the early and advanced phases. While worsening of parkinsonism was the most important factor, age at diagnosis, emergence of visual hallucinations, and possibly dementia were also associated with weight loss. We demonstrated significant weight loss in PD patients compared to controls over approximately 1 decade. Neurodegeneration involving both motor and nonmotor systems may be associated with weight loss in PD.

A recommended scale for cognitive screening in clinical trials of Parkinson's disease

Cognitive impairment is common in Parkinsons disease (PD). There is a critical need for a brief, standard cognitive screening measure for use in PD trials whose primary focus is not on cognition. The Parkinson Study Group (PSG) Cognitive/Psychiatric Working Group formed a Task Force to make recommendations for a cognitive scale that could screen for dementia and mild cognitive impairment in clinical trials of PD where cognition is not the primary outcome. This Task Force conducted a systematic literature search for cognitive assessments previously used in a PD population. Scales were then evaluated for their appropriateness to screen for cognitive deficits in clinical trials, including brief administration time (<15 minutes), assessment of the major cognitive domains, and potential to detect subtle cognitive impairment in PD. Five scales of global cognition met the predetermined screening criteria and were considered for review. Based on the Task Forces evaluation criteria the Montreal Cognitive Assessment (MoCA), appeared to be the most suitable measure. This Task Force recommends consideration of the MoCA as a minimum cognitive screening measure in clinical trials of PD where cognitive performance is not the primary outcome measure. The MoCA still requires further study of its diagnostic utility in PD populations but appears to be the most appropriate measure among the currently available brief cognitive assessments. Widespread adoption of a single instrument such as the MoCA in clinical trials can improve comparability between research studies on PD.