The human subthalamic nucleus transiently inhibits active attentional processes.

The subthalamic nucleus (STN) of the basal ganglia is key to the inhibitory control of movement. Consequently, it is a primary target for the neurosurgical treatment of movement disorders like Parkinson's disease, where modulating the STN via deep brain stimulation (DBS) can release excess inhibition of thalamocortical motor circuits. However, the STN is also anatomically connected to other thalamocortical circuits, including those underlying cognitive processes like attention. Notably, STN-DBS can also affect these processes. This suggests that the STN may also contribute to the inhibition of non-motor activity and that STN-DBS may cause changes to this inhibition. Here we tested this hypothesis in humans. We used a novel, wireless outpatient method to record intracranial local field potentials (LFP) from STN DBS implants during a visual attention task (Experiment 1, n = 12). These outpatient measurements allowed the simultaneous recording of high-density EEG, which we used to derive the steady state visual evoked potential (SSVEP), a well established neural index of visual attentional engagement. By relating STN activity to this neural marker of attention (instead of overt behaviour), we avoided possible confounds resulting from STN's motor role. We aimed to test whether the STN contributes to the momentary inhibition of the SSVEP caused by unexpected, distracting sounds. Furthermore, we causally tested this association in a second experiment, where we modulated STN via DBS across two sessions of the task, spaced at least 1 week apart (n = 21, no sample overlap with Experiment 1). The LFP recordings in Experiment 1 showed that reductions of the SSVEP after distracting sounds were preceded by sound-related γ-frequency (>60 Hz) activity in the STN. Trial-to-trial modelling further showed that this STN activity statistically mediated the sounds' suppressive effect on the SSVEP. In Experiment 2, modulating STN activity via DBS significantly reduced these sound-related SSVEP reductions. This provides causal evidence for the role of the STN in the surprise-related inhibition of attention. These findings suggest that the human STN contributes to the inhibition of attention, a non-motor process. This supports a domain-general view of the inhibitory role of the STN. Furthermore, these findings also suggest a potential mechanism underlying some of the known cognitive side effects of STN-DBS treatment, especially on attentional processes. Finally, our newly established outpatient LFP recording technique facilitates the testing of the role of subcortical nuclei in complex cognitive tasks, alongside recordings from the rest of the brain, and in much shorter time than peri-surgical recordings.

Reprint of: The impact of alpha-1-adrenergic receptor antagonists on the progression of Parkinson disease.

BACKGROUND: Alpha-1-adrenergic receptor antagonists (AARAs) are used in the treatment of benign prostatic hypertrophy. Some AARAs, such as terazosin, stimulate glycolysis and increase cellular adenosine triphosphate levels through activation of phosphoglycerate kinase 1 (PGK1), which has been suggested to be of therapeutic benefit in patients with Parkinson disease (PD). OBJECTIVE: This study aimed to determine whether exposure to PGK1-activating AARAs was associated with slower PD progression. METHODS: National Veterans Affairs administrative data were used to identify patients who initiated PD-related pharmacotherapy during 2000 to 2019 and were concurrently prescribed an AARA. Using a retrospective cohort design, the count of incident PD-related outcome events within 1 year of follow-up was contrasted between patients prescribed a PGK1-activating AARA versus tamsulosin (an AARA without PKG1 stimulation), using multivariable negative binomial regression. PD-related outcome events were identified using ICD codes indicating motor symptoms, nonmotor symptoms, and other potential complications as clinical markers for the progression of PD. RESULTS: A total of 127,142 patients initiated drug therapy for PD during the observation period, of whom 24,539 concurrently received an AARA. Incident PD-related events were observed significantly less often in patients receiving a PGK1 AARA (n = 14,571) than tamsulosin (n = 9968) (incidence rate ratio [IRR] 0.80 [95% CI 0.77-0.83]). These results remained significant after adjustment for confounding factors (IRR 0.85 [95% CI 0.81-0.88]) and in sensitivity analyses. CONCLUSION: Patients prescribed a PGK1-activating AARA experienced fewer PD-related outcome events than patients prescribed tamsulosin. These results may indicate a role for terazosin and other PGK1 activators in slowing disease progression of PD; however, randomized controlled trials are needed.

The impact of alpha-1-adrenergic receptor antagonists on the progression of Parkinson disease.

BACKGROUND: Alpha-1-adrenergic receptor antagonists (AARAs) are used in the treatment of benign prostatic hypertrophy. Some AARAs, such as terazosin, stimulate glycolysis and increase cellular adenosine triphosphate levels through activation of phosphoglycerate kinase 1 (PGK1), which has been suggested to be of therapeutic benefit in patients with Parkinson disease (PD). OBJECTIVE: This study aimed to determine whether exposure to PGK1-activating AARAs was associated with slower PD progression. METHODS: National Veterans Affairs administrative data were used to identify patients who initiated PD-related pharmacotherapy during 2000 to 2019 and were concurrently prescribed an AARA. Using a retrospective cohort design, the count of incident PD-related outcome events within 1 year of follow-up was contrasted between patients prescribed a PGK1-activating AARA versus tamsulosin (an AARA without PKG1 stimulation), using multivariable negative binomial regression. PD-related outcome events were identified using ICD codes indicating motor symptoms, nonmotor symptoms, and other potential complications as clinical markers for the progression of PD. RESULTS: A total of 127,142 patients initiated drug therapy for PD during the observation period, of whom 24,539 concurrently received an AARA. Incident PD-related events were observed significantly less often in patients receiving a PGK1 AARA (n = 14,571) than tamsulosin (n = 9968) (incidence rate ratio [IRR] 0.80 [95% CI 0.77-0.83]). These results remained significant after adjustment for confounding factors (IRR 0.85 [95% CI 0.81-0.88]) and in sensitivity analyses. CONCLUSION: Patients prescribed a PGK1-activating AARA experienced fewer PD-related outcome events than patients prescribed tamsulosin. These results may indicate a role for terazosin and other PGK1 activators in slowing disease progression of PD; however, randomized controlled trials are needed.

Separating the effect of reward from corrective feedback during learning in patients with Parkinson's disease.

Parkinson's disease (PD) is associated with procedural learning deficits. Nonetheless, studies have demonstrated that reward-related learning is comparable between patients with PD and controls (Bódi et al., Brain, 132(9), 2385-2395, 2009; Frank, Seeberger, & O'Reilly, Science, 306(5703), 1940-1943, 2004; Palminteri et al., Proceedings of the National Academy of Sciences of the United States of America, 106(45), 19179-19184, 2009). However, because these studies do not separate the effect of reward from the effect of practice, it is difficult to determine whether the effect of reward on learning is distinct from the effect of corrective feedback on learning. Thus, it is unknown whether these group differences in learning are due to reward processing or learning in general. Here, we compared the performance of medicated PD patients to demographically matched healthy controls (HCs) on a task where the effect of reward can be examined separately from the effect of practice. We found that patients with PD showed significantly less reward-related learning improvements compared to HCs. In addition, stronger learning of rewarded associations over unrewarded associations was significantly correlated with smaller skin-conductance responses for HCs but not PD patients. These results demonstrate that when separating the effect of reward from the effect of corrective feedback, PD patients do not benefit from reward.

Use, maintenance and dose effects of cognitive speed of processing training in Parkinson's disease.

INTRODUCTION: Recent research indicated that cognitive speed of processing training (SPT) improved Useful Field of View (UFOV) among individuals with Parkinson's disease (PD). The effects of SPT in PD have not been further examined. The objectives of the current study were to investigate use, maintenance and dose effects of SPT among individuals with PD. METHODS: Participants who were randomized to SPT or a delayed control group completed the UFOV at a six-month follow-up visit. Use of SPT was monitored across the six-month study period. Regression explored factors affecting SPT use. Mixed effect models were conducted to examine the durability of training gains among those randomized to SPT (n = 44), and training dose effects among the entire sample (n = 87). RESULTS: The majority of participants chose to continue to use SPT (52%). Those randomized to SPT maintained improvements in UFOV performance. A significant dose effect of SPT was evident such that more hours of training were associated with greater UFOV performance improvements. The cognitive benefits derived from SPT in PD may be maintained for up to three months. CONCLUSION: Future research should determine how long gains endure and explore if such training gains transfer.

Cognitive impairment and dementia in Parkinson's disease: practical issues and management.

Cognitive impairment and dementia pose particular challenges in the management of patients with Parkinson's disease (PD). Decision-making capacity can render patients vulnerable in a way that requires careful ethical considerations by clinicians with respect to medical decision making, research participation, and public safety. Clinicians should discuss how future decisions will be made as early in the disease course as possible. Because of cognitive, visual, and motor impairments, PD may be associated with unsafe driving, leading to early driving cessation in many. DBS of the STN and, to a lesser degree, globus pallidus interna (GPi) has consistently been associated with decreased verbal fluency, but significant global cognitive decline is usually not observed in patients who undergo rigorous selection. There are some observations suggesting lesser cognitive decline in GPi DBS than STN DBS, but further research is required. Management of PD dementia (PDD) patients involves both pharmacological and nonpharmacological measures. Patients with PDD should be offered treatment with a cholinesterase inhibitor taking into account expected benefits and potential risks. Treatment with neuroleptics may be necessary to treat psychosis; classical neuroleptics, as well as risperidone and olanzapine, should be avoided. Quetiapine might be considered first-line treatment because it does not need special monitoring, although the strongest evidence for efficacy exists for clozapine. Evidence from randomized, controlled studies in the PDD population is lacking; selective serotonin reuptake inhibitors or serotonin-norepinephrine reuptake inhibitors may be used to treat depressive features. Clonazepam or melatonin may be useful in the treatment of rapid eye movement behavior disorder.

Digital driving data can track driving exposure and quality of life in Parkinson's disease.

OBJECTIVE: Parkinson's disease (PD) impairs motor and non-motor functions. Driver strategies to compensate for impairments, like avoiding driving in risky environments, may reduce on-road risk at the cost of decreasing driver mobility, independence, and quality of life (QoL). It is unclear how PD symptoms link to driving risk exposure, strategies, and QoL. We assessed associations between PD symptoms and driving exposure (1) overall, (2) in risky driving environments, and (3) in relationship to QoL. METHODS: Twenty-eight drivers with idiopathic PD were assessed using the Movement Disorders Society-Unified Parkinson's Disease Rating Scale (MDS-UPDRS) and RAND 36-Item Short Form Health Survey (SF-36). Real-world driving was monitored for 1 month. Overall driving exposure (miles driven) and risky driving exposure (miles driven in higher risk driving environments) were assessed across PD symptom severity. High traffic, night, and interstate roads were considered risky environments. RESULTS: 18,642 miles (30,001 km) driven were collected. Drivers with PD with worse motor symptoms (MDS-UPDRS Part III) drove more overall (b = 0.17, P < .001) but less in risky environments (night: b = -0.35, P < .001; interstate roads: b = -0.23, P < .001; high traffic: b = -0.14, P < .001). Worse non-motor daily activities symptoms (MDS-UPDRS Part I) did not affect overall driving exposure (b = -0.05, P = .43) but did affect risky driving exposure. Worse non-motor daily activities increased risk exposure to interstate (b = 0.36, P < .001) and high traffic (b = 0.09, P = .03) roads while reducing nighttime risk exposure (b = -0.15, P = .01). Daily activity impacts from motor symptoms (MDS-UPDRS Part II) did not affect distance driven. Reduced driving exposure (number of drives per day) was associated with worse physical health-related QoL (b = 2.87, P = .04). CONCLUSIONS: Results provide pilot data revealing specific PD symptom impacts on driving risk exposure and QoL. Drivers with worse non-motor impairments may have greater risk exposure. In contrast, drivers with worse motor impairments may have reduced driver risk exposure. Reduced driving exposure may worsen physical health-related QoL. Results show promise for using driving to inform clinical care.

Resting-state EEG measures cognitive impairment in Parkinson's disease.

Cognitive dysfunction is common in Parkinson's disease (PD). We developed and evaluated an EEG-based biomarker to index cognitive functions in PD from a few minutes of resting-state EEG. We hypothesized that synchronous changes in EEG across the power spectrum can measure cognition. We optimized a data-driven algorithm to efficiently capture these changes and index cognitive function in 100 PD and 49 control participants. We compared our EEG-based cognitive index with the Montreal cognitive assessment (MoCA) and cognitive tests across different domains from National Institutes of Health (NIH) Toolbox using cross-validations, regression models, and randomization tests. Finally, we externally validated our approach on 32 PD participants. We observed cognition-related changes in EEG over multiple spectral rhythms. Utilizing only 8 best-performing electrodes, our proposed index strongly correlated with cognition (MoCA: rho = 0.68, p value < 0.001; NIH-Toolbox cognitive tests: rho ≥ 0.56, p value < 0.001) outperforming traditional spectral markers (rho = -0.30-0.37). The index showed a strong fit in regression models (R2 = 0.46) with MoCA, yielded 80% accuracy in detecting cognitive impairment, and was effective in both PD and control participants. Notably, our approach was equally effective (rho = 0.68, p value < 0.001; MoCA) in out-of-sample testing. In summary, we introduced a computationally efficient data-driven approach for cross-domain cognition indexing using fewer than 10 EEG electrodes, potentially compatible with dynamic therapies like closed-loop neurostimulation. These results will inform next-generation neurophysiological biomarkers for monitoring cognition in PD and other neurological diseases.

A pilot dose-finding study of Terazosin in humans.

Background: Parkinson's disease (PD) is a prevalent neurodegenerative disorder where progressive neuron loss is driven by impaired brain bioenergetics, particularly mitochondrial dysfunction and disrupted cellular respiration. Terazosin (TZ), an α-1 adrenergic receptor antagonist with a known efficacy in treating benign prostatic hypertrophy and hypertension, has shown potential in addressing energy metabolism deficits associated with PD due to its action on phosphoglycerate kinase 1 (PGK1). This study aimed to investigate the safety, tolerability, bioenergetic target engagement, and optimal dose of TZ in neurologically healthy subjects. Methods: Eighteen healthy men and women (60 - 85 years old) were stratified into two cohorts based on maximum TZ dosages (5 mg and 10 mg daily). Methods included plasma and cerebrospinal fluid TZ concentration measurements, whole blood ATP levels, 31 Phosphorous magnetic resonance spectroscopy for brain ATP levels, 18 F-FDG PET imaging for cerebral metabolic activity, and plasma metabolomics. Results: Our results indicated that a 5 mg/day dose of TZ significantly increased whole blood ATP levels and reduced global cerebral 18 F-FDG PET uptake without significant side effects or orthostatic hypotension. These effects were consistent across sexes. Higher doses did not result in additional benefits and showed a potential biphasic dose-response. Conclusions: TZ at a dosage of 5 mg/day engages its metabolic targets effectively in both sexes without inducing significant adverse effects and provides a promising therapeutic avenue for mitigating energetic deficiencies. Further investigation via clinical trials to validate TZ's efficacy and safety in neurodegenerative (i.e., PD) contexts is warranted.

Prefrontal dopamine signaling and cognitive symptoms of Parkinson's disease.

Cognitive dysfunction is a common symptom of Parkinson's disease (PD) that causes significant morbidity and mortality. The severity of these symptoms ranges from minor executive symptoms to frank dementia involving multiple domains. In the present review, we will concentrate on the aspects of cognitive impairment associated with prefrontal dopaminergic dysfunction, seen in non-demented patients with PD. These symptoms include executive dysfunction and disorders of thought, such as hallucinations and psychosis. Such symptoms may go on to predict dementia related to PD, which involves amnestic dysfunction and is typically seen later in the disease. Cognitive symptoms are associated with dysfunction in cholinergic circuits, in addition to the abnormalities in the prefrontal dopaminergic system. These circuits can be carefully studied and evaluated in PD, and could be leveraged to treat difficult clinical problems related to cognitive symptoms of PD.

Impact of specific executive functions on driving performance in people with Parkinson's disease.

Executive functions encompass various cognitive processes and are critical in novel or demanding driving situations. Our aim was to determine the role of impairments in specific executive functions (updating, flexibility, inhibition) on road performance in drivers with Parkinson's disease (PD), a condition commonly associated with early executive dysfunction. In this pilot study, 19 patients with mild to moderate PD and 21 healthy controls matched for age, education, and driving experience were tested using a neuropsychological battery assessing global cognitive abilities, updating (n-back task), flexibility (plus-minus task), and inhibition (Stroop test). Participants also underwent a 45-minute road test in which they were scored by a driving instructor and a second experimenter. To separate "at-risk" drivers from safe drivers, a composite driving indicator was calculated from the Test Ride for Investigating Practical Fitness to Drive score, the penalty score from the observation grid, and the number of safety interventions made by the driving instructor. Eight of the 40 drivers (all PD) were rated as "at risk." Measures of updating (the n-back task) and mental flexibility (the plus-minus task) predicted driving safety even after adjustment for group status, explaining 53% of the total variance. These 2 tests also discriminated between safe and "at-risk" drivers within the PD group. These findings, although preliminary, suggest that updating and mental flexibility are critical for safe driving in PD. Assessment batteries for driving fitness should probe different aspects of executive functions, specifically when evaluating drivers with PD.

Validation of a screening battery to predict driving fitness in people with Parkinson's disease.

BACKGROUND: We previously developed a short clinical battery, consisting of contrast sensitivity, Clinical Dementia Rating, the Unified Parkinson's Disease Rating Scale-motor section (UPDRS III), and disease duration, which correctly classified 90% of drivers with Parkinson's Disease (PD). The aim of this study was to validate that screening battery in a different sample of PD drivers. METHODS: Sixty drivers with PD were enrolled to validate our original screening battery to predict driving fitness decisions (pass-fail) by a state agency where drivers underwent detailed visual, cognitive, and on-road testing. RESULTS: Twenty-four participants (40%) failed the driving evaluation. The screening battery correctly classified 46 (77%) participants (sensitivity and negative predictive value = 96%; specificity and positive predictive value = 64%). Adding other clinical predictors (e.g., age of onset, Hoehn-Yahr stage instead of UPDRS III) failed to improve the specificity of the model when the sensitivity was kept constant at 96%. However, a driving simulator evaluation improved the specificity of the model to 94%. CONCLUSIONS: The original clinical battery proved to be a valid screening tool that accurately identifies fit drivers with PD and select those who need more detailed testing at specialized centers.

Driving and off-road impairments underlying failure on road testing in Parkinson's disease.

Parkinson's disease (PD) affects driving ability. We aimed to determine the most critical impairments in specific road skills and in clinical characteristics leading to failure on a road test in PD. In this cross-sectional study, certified driving assessment experts evaluated specific driving skills in 104 active, licensed drivers with PD using a standardized, on-road checklist and issued a global decision of pass/fail. Participants also completed an off-road evaluation assessing demographic features, disease characteristics, motor function, vision, and cognition. The most important driving skills and off-road predictors of the pass/fail outcome were identified using multivariate stepwise regression analyses. Eighty-six (65%) passed and 36 (35%) failed the on-road driving evaluation. Persons who failed performed worse on all on-road items. When adjusted for age and gender, poor performances on lateral positioning at low speed, speed adaptations at high speed, and left turning maneuvers yielded the best model that determined the pass/fail decision (R(2) = 0.56). The fail group performed poorer on all motor, visual, and cognitive tests. Measures of visual scanning, motor severity, PD subtype, visual acuity, executive functions, and divided attention were independent predictors of pass/fail decisions in the multivariate model (R(2) = 0.60). Our study demonstrated that failure on a road test in PD is determined by impairments in specific driving skills and associated with deficits in motor, visual, executive, and visuospatial functions. These findings point to specific driving and off-road impairments that can be targeted in multimodal rehabilitation programs for drivers with PD.

Real-World Driving Data Indexes Dopaminergic Treatment Effects in Parkinson's Disease.

Background: Driving is a complex, everyday task that impacts patient agency, safety, mobility, social connections, and quality of life. Digital tools can provide comprehensive real-world (RW) data on driver behavior in patients with Parkinson's disease (PD), providing critical data on disease status and treatment efficacy in the patient's own environment. Objective: This pilot study examined the use of driving data as a RW digital biomarker of PD symptom severity and dopaminergic therapy effectiveness. Methods: Naturalistic driving data (3974 drives) were collected for 1 month from 30 idiopathic PD drivers treated with dopaminergic medications. Prescriptions data were used to calculate levodopa equivalent daily dose (LEDD). The association between LEDD and driver mobility (number of drives) was assessed across PD severity, measured by the Movement Disorder Society Unified Parkinson's Disease Rating Scale (MDS-UPDRS). Results: PD drivers with worse motor symptoms based on self-report (Part II: P = 0.02) and clinical examination (Part III: P < 0.001) showed greater decrements in driver mobility. LEDD levels >400 mg/day were associated with higher driver mobility than those with worse PD symptoms (Part I: P = 0.02, Part II: P < 0.001, Part III: P < 0.001). Conclusions: Results suggest that comprehensive RW driving data on PD patients may index disease status and treatment effectiveness to improve patient symptoms, safety, mobility, and independence. Higher dopaminergic treatment may enhance safe driver mobility in PD patients with worse symptom severity.

Clinical predictors of driving status in Huntington's disease.

The aim of this study was to identify the motor, cognitive, and behavioral determinants of driving status and risk factors for driving cessation in Huntington's disease (HD). Seventy-four patients with HD were evaluated for cognitive, motor, psychiatric, and functional status using a standardized battery (Unified Huntington's Disease Rating Scale [UHDRS] and supplemental neuropsychological testing) during a research clinic visit. Chart review was used to categorize patients into two driving status categories: (1) "currently driving" included those driving and driving but with clinician recommendation to restrict, and (2) "not driving" included those with clinician recommendation to cease driving and those not currently driving because of HD. Multi- and univariate logistic regression was used to identify significant clinical predictors of those driving versus not driving. Global cognitive performance and UHDRS Total Functional Capacity scores provided the best predictive model of driving cessation (Nagelkerke R(2) = 0.65; P < 0.0001). Measures of learning (P = 0.006) and psychomotor speed/attention (P = 0.003) accounted for the overall cognitive finding. In univariate analyses, numerous cognitive, motor, and daily functioning items were significantly associated with driving. Although driving status is associated with many aspects of the disease, results suggest that the strongest association is with cognitive performance. A detailed cognitive evaluation is an important component of multidisciplinary clinical assessment in patients with HD who are driving.

Real-life consequences of cognitive dysfunction in Parkinson's disease.

While motor symptoms are the most recognized features of Parkinson's disease (PD), cognitive dysfunction is a key determinant of consequences of PD in real-life. In this chapter we review important domains where cognitive dysfunction negatively impacts the lives of people with PD (PwPD), such as difficulties in occupational and social life, and instrumental ADLs such as driving. Early loss of employment has important effects for PwPD, their families, and society. PwPD experience higher rates of family and social discord as well as important changes in their social roles. These processes are largely mediated through cognitive dysfunction, particularly difficulties processing and understanding emotions, decreased attention, and executive dysfunction. Cognitive dysfunction is also an important mediator of driving impairments, which contributes to decreased independence in PwPD. Finally, we briefly review the costs associated with cognitive impairment in PD. Both indirect and direct costs for PwPD with cognitive impairment are substantially higher than for PwPD with normal cognition.

A pilot to assess target engagement of terazosin in Parkinson's disease.

BACKGROUND: Impaired brain energy metabolism is a key feature of Parkinson's disease (PD). Terazosin (TZ) binds phosphoglycerate kinase 1 and stimulates its activity, which enhances glycolysis and increases ATP levels. Preclinical and epidemiologic data suggest that TZ may be neuroprotective in PD. We aimed to assess target engagement and safety of TZ in people with PD. METHODS: We performed a 12-week pilot study in people with PD. Participants were randomized to receive 5 mg TZ or placebo. Participants and study personnel were blinded. We assessed TZ target engagement by measuring brain ATP with 31P-magnetic resonance spectroscopy (MRS) and whole blood ATP with a luminescence assay. Robust linear regression models compared changes between groups controlling for baseline brain and blood ATP levels, respectively. We also assessed clinical measures of PD and adverse events. RESULTS: Thirteen participants were randomized. Mild dizziness/lightheadedness was more common in the TZ group, and three participants taking TZ dropped out because of dizziness and/or orthostatic hypotension. Compared to the placebo group, the TZ group had a significant increase in the ratio of ßATP to inorganic phosphate in the brain. The TZ group also had a significant increase in blood ATP levels compared to the placebo group (p < 0.01). CONCLUSIONS: This pilot study suggests that TZ may engage its target and change ATP levels in the brain and blood of people with PD. Further studies may be warranted to test the disease-modifying potential of TZ.

Driving difficulties in Parkinson's disease.

Safe driving requires the coordination of attention, perception, memory, motor and executive functions (including decision-making) and self-awareness. Parkinson's disease and other disorders may impair these abilities. Because age or medical diagnosis alone is often an unreliable criterion for licensure, decisions on fitness to drive should be based on empirical observations of performance. Linkages between cognitive abilities measured by neuropsychological tasks, and driving behavior assessed using driving simulators, and natural and naturalistic observations in instrumented vehicles, can help standardize the assessment of fitness-to-drive. By understanding the patterns of driver safety errors that cause crashes, it may be possible to design interventions to reduce these errors and injuries and increase mobility. This includes driver performance monitoring devices, collision alerting and warning systems, road design, and graded licensure strategies.

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

Cognitive impairment is common in Parkinson's 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 Force's 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.

Prediction of driving ability with neuropsychological tests: demographic adjustments diminish accuracy.

Demographically adjusted norms generally enhance accuracy of inferences based on neuropsychological assessment. However, we hypothesized that demographic corrections diminish predictive accuracy for real-world activities with absolute cognitive demands. Driving ability was assessed with a 45-minute drive along a standardized on-road route in participants aged 65+ (24 healthy elderly, 26 probable Alzheimer's disease, 33 Parkinson's disease). Neuropsychological measures included: Trail-Making A and B, Complex Figure, Benton Visual Retention, and Block Design tests. A multiple regression model with raw neuropsychological scores was significantly predictive of driving errors (R2 = .199, p = .005); a model with demographically adjusted scores was not (R2 = .113, p = .107). Raw scores were more highly correlated with driving errors than were adjusted scores for each neuropsychological measure, and among healthy elderly and Parkinson's patients. When predicting real-world activities that depend on absolute levels of cognitive abilities regardless of demographic considerations, predictive accuracy is diminished by demographic corrections.