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Objective: This study was undertaken to compare the rate of change in cognition between glucocerebrosidase (GBA) mutation carriers and noncarriers with and without subthalamic nucleus deep brain stimulation (STN-DBS) in Parkinson disease. Methods: Clinical and genetic data from 12 datasets were examined. Global cognition was assessed using the Mattis Dementia Rating Scale (MDRS). Subjects were examined for mutations in GBA and categorized as GBA carriers with or without DBS (GBA+DBS+, GBA+DBS-), and noncarriers with or without DBS (GBA-DBS+, GBA-DBS-). GBA mutation carriers were subcategorized according to mutation severity (risk variant, mild, severe). Linear mixed modeling was used to compare rate of change in MDRS scores over time among the groups according to GBA and DBS status and then according to GBA severity and DBS status. Results: Data were available for 366 subjects (58 GBA+DBS+, 82 GBA+DBS-, 98 GBA-DBS+, and 128 GBA-DBS- subjects), who were longitudinally followed (range = 36–60 months after surgery). Using the MDRS, GBA+DBS+ subjects declined on average 2.02 points/yr more than GBA-DBS- subjects (95% confidence interval [CI] = −2.35 to −1.69), 1.71 points/yr more than GBA+DBS- subjects (95% CI = −2.14 to −1.28), and 1.49 points/yr more than GBA-DBS+ subjects (95% CI = −1.80 to −1.18). Interpretation: Although not randomized, this composite analysis suggests that the combined effects of GBA mutations and STN-DBS negatively impact cognition. We advise that DBS candidates be screened for GBA mutations as part of the presurgical decision-making process. We advise that GBA mutation carriers be counseled regarding potential risks associated with STN-DBS so that alternative options may be considered. ANN NEUROL 2022;91:424–435.

Background: The criteria for PD-MCI allow the use of global cognitive tests. Their predictive value for conversion from PD-MCI to PDD, especially compared to comprehensive neuropsychological assessment, is unknown. Methods: The MDS PD-MCI Study Group combined four datasets containing global cognitive tests as well as a comprehensive neuropsychological assessment to define PD-MCI (n = 467). Risk for developing PDD was examined using a Cox model. Global cognitive tests were compared to neuropsychological test batteries (Level I&II) in determining risk for PDD. Results: PD-MCI based on a global cognitive test (MMSE or MoCA) increases the hazard for developing PDD (respectively HR = 2.57, P = 0.001; HR = 4.14, P =

Background Few studies assess the relationships between nonmotor aspects of experiences of daily living and cognitive functioning in Parkinson's disease (PD). Objective To evaluate the relationships among the Movement Disorders Society-Unified Parkinson's Disease Rating Scale (MDS-UPDRS) part I items and neuropsychological tests in PD.Methods: We assessed 151 PD patients with the MDS-UPDRS part I and a battery of cognitive tests focused on the following 5 cognitive domains: attention/working memory, executive functioning, recent memory, language, visuoperception. Raw scores for individual cognitive tests were transformed to z scores, and cognitive domain scores were calculated by averaging z scores within each domain. Individual items from the MDS-UPDRS part I were entered in a stepwise linear regression analysis assessing item contribution to cognitive domain scores. Results The MDS-UPDRS part I item scores for hallucinations and psychosis and light headedness on standing predicted attention/working memory domain scores (P = 0.004). These same item scores, along with apathy, depressed mood, and dopamine dysregulation syndrome, predicted executive functioning (P = 0.044). The apathy and dopamine dysregulation syndrome items predicted language (P = 0.006). In addition, the cognitive impairment and sleep items were predictors of recent memory (P = 0.031). None of the items were predictors of visuoperception (P = 0.006). Other part I items were not significantly related to cognitive domain scores. Conclusions Specific nonmotor MDS-UPDRS part I items, particularly mood, behavior, and autonomic-related items, exhibited significant relationships with cognitive domains. The highest number of items were predictive of the executive functioning domain, which is the hallmark cognitive dysfunction in PD.

BACKGROUND: Huntington's disease (HD) is characterized by chorea, balance and gait impairments, and cognitive deficits, which increase fall risk. Dual task (DT) and environmentally challenging paradigms reflect balance related to everyday life. Furthermore, the impact of cognitive deficits on balance dysfunction and falls in HD is unknown. OBJECTIVE: To determine the impact of DT interference, sensory feedback, and cognitive performance on balance and falls in HD. METHODS: Seventeen participants with HD (55 ± 9.7 years) and 17 age‐matched controls (56.5 ± 9.3 years) underwent quantitative balance testing with APDM inertial sensors. Postural sway was assessed during conditions of manipulated stance, vision, proprioception, and cognitive demand. The DT was a concurrent verbal fluency task. Neuropsychological assessments testing multiple cognitive domains were also administered. RESULTS: HD participants exhibited significantly greater total sway area, jerk, and variability under single‐task (ST) and DT conditions compared to controls (P = 0.0002 – < 0.0001). They also demonstrated greater DT interference with vision removed for total sway area (P = 0.01) and variability (P = 0.02). Significantly worse postural control was observed in HD with vision removed and reduced proprioception (P = 0.001 – 0.01). Decreased visuospatial performance correlated with greater total sway and jerk (P = 0.01; 0.009). No balance parameters correlated with retrospective falls in HD. CONCLUSIONS: HD participants have worse postural control under DT, limited proprioception/vision, and greater DT interference with a narrowed base and no visual input. These findings may have implications for designing motor and cognitive strategies to improve balance in HD.

Huntington's disease (HD) is characterized by motor, cognitive, and psychiatric dysfunction. HD progression causes loss of automaticity, such that previously automatic tasks require greater attentional resources. Dual-task (DT) paradigms and fast-paced gait may stress the locomotor system, revealing deficits not seen under single-task (ST). However, the impact of gait "stress tests" on HD individuals needs further investigation. Therefore, the aims of this study were to investigate whether: 1) fast-paced and dual-task walking uncover deficits in gait and turning not seen under single-task, 2) cognitive and gait outcomes relate to fall incidence, and 3) gait deficits measured with wearable inertial sensors correlate with motor symptom severity in HD as measured by the Unified Huntington's disease Rating Scale-total motor score (UHDRS-TMS). Seventeen HD (55 ± 9.7 years) and 17 age-matched controls (56.5 ± 9.3 years) underwent quantitative gait testing via a 25m, two-minute walk test with APDMTM inertial sensors. Gait was assessed under a 1) ST, self-selected pace, 2) fast-as-possible (FAP) pace, and 3) verbal fluency DT. The UHDRS-TMS and a cognitive test battery were administered, and a retrospective fall history was obtained. During ST, DT, and FAP conditions, HD participants demonstrated slower gait, shorter stride length, and greater lateral step and stride length variability compared to controls (p

Background Erectile dysfunction (ED) is a common nonmotor feature in patients with Parkinson's disease (PD). Data regarding the tolerability and efficacy of anti-ED medication in the PD population are limited. The aim of this work was to assess the safety and efficacy of sildenafil in treatment of ED in men with PD. Methods This was a double-blind, placebo-controlled, cross-over study consisting of two 4-week arms separated by a 2-week washout period. Treatment sequence (placebo-sildenafil vs. sildenafil-placebo) was randomized. Sildenafil was started at 50 mg and adjusted to 25, 50, or 100 mg after 2 weeks, depending upon side effects. The Erectile Function domain of the International Index of Erectile Function (IIEF-EF; primary outcome measure) and the Parkinson's Disease Quality of Life (secondary outcome measure) were obtained at baseline and end of each treatment period. The UPDRS was obtained at each study visit. The difference between group means was tested for statistical significance using t tests. Results Twenty men participated and completed both treatment arms of the study. There was one instance of headache as a side effect. There was a significant effect of sildenafil on sexual functioning as measured by the IIEF-EF domain (P < 0.0001; mean for sildenafil = 23.2 ± 7.0; mean for placebo = 12.3 ± 7.5). There were no treatment effects for quality of life (P = 0.3) or PD symptoms (P = 0.86). Conclusions Sildenafil was safe and improved ED in this sample of men with PD. Overall, PD symptoms and quality of life were not impacted by use of sildenafil.

Women who carry fragile X mental retardation 1 (FMR1)gene premutation expansions frequently report neurological or endocrine symptoms and prior studies have predominantly focused on questionnaire report of medical issues. Premutation carrier (PMC) women (n = 33) and non-carrier controls (n = 13) were recruited and evaluated by a neurologist, neuropsychologist, and endocrinologist. Blood and skin biopsies were collected for molecular measures. Scales for movement disorders, neuropathy, cognitive function, psychiatric symptoms, sleep, and quality of life were completed. The average age of the women was 51 years (n = 46) and average CGG repeat size was 91 ± 24.9 in the FMR1 PMC women. Seventy percent of the PMC women had an abnormal neurological examination. PMC women had significantly higher scores on the Fragile X-Associated Tremor Ataxia Syndrome (FXTAS) rating scale, more neuropathy, and difficulty with tandem gait compared to controls. Central sensitivity syndromes, a neuroticism profile on the NEO Personality Profile, and sleep disorders were also prevalent. Discrepancies between subject report and examination findings were also seen. This pilot study suggests that women with the FMR1 premutation may have a phenotype that overlaps with that seen in FXTAS. Additional research with larger sample sizes is warranted to better delineate the clinical features.

Background Loss-of-function mutations in the GBA gene are associated with more severe cognitive impairment in PD, but the nature of these deficits is not well understood and whether common GBA polymorphisms influence cognitive performance in PD is not yet known. Methods We screened the GBA coding region for mutations and the E326K polymorphism in 1,369 PD patients enrolled at eight sites from the PD Cognitive Genetics Consortium. Participants underwent assessments of learning and memory (Hopkins Verbal Learning Test–Revised), working memory/executive function (Letter-Number Sequencing Test and Trail Making Test A and B), language processing (semantic and phonemic verbal fluency), visuospatial abilities (Benton Judgment of Line Orientation), and global cognitive function (MoCA). We used linear regression to test for association between genotype and cognitive performance with adjustment for important covariates and accounted for multiple testing using Bonferroni's corrections. Results Mutation carriers (n = 60; 4.4%) and E326K carriers (n = 65; 4.7%) had a higher prevalence of dementia (mutations, odds ratio = 5.1; P = 9.7 × 10−6; E326K, odds ratio = 6.4; P = 5.7 × 10−7) and lower performance on Letter-Number Sequencing (mutations, corrected P[Pc] = 9.0 × 10−4; E326K, Pc = 0.036), Trail Making B-A (mutations, Pc = 0.018; E326K, Pc = 0.018), and Benton Judgment of Line Orientation (mutations, Pc = 0.0045; E326K, Pc = 0.0013). Conclusions Both GBA mutations and E326K are associated with a distinct cognitive profile characterized by greater impairment in working memory/executive function and visuospatial abilities in PD patients. The discovery that E326K negatively impacts cognitive performance approximately doubles the proportion of PD patients we now recognize are at risk for more severe GBA-related cognitive deficits. © 2015 International Parkinson and Movement Disorder Society

Objective We examined tolerability of preoperative neuropsychological testing (the Core Assessment Program for Surgical Interventional Therapies in Parkinson's Disease [CAPSIT-PD] protocol) for DBS. We also examined factors that may influence tolerability, including fatigue, global cognitive function, depression, and patient-based characteristics. Methods In this retrospective study, we reviewed preoperative neuropsychological testing results from 35 patients who were scheduled to undergo DBS. We examined the overall tolerability of the full battery and the tolerability of each test. We placed attention on a test's placement in the fixed order of the battery to measure whether there was a clustering of poorly tolerated tests toward the end of the battery as an indication of fatigue. Spearman's rank correlation was used to determine the relationship between tolerability and (1) global cognitive function, (2) depression, and (3) patient-based characteristics. Results Fourteen subjects (40%) were able to tolerate the full battery and completed all 10 tests. The domains that were least tolerated pertained to executive function and procedural memory. There was a consistent time-based tolerability pattern that was observed. There was a significant correlation between tolerability and global cognitive function (ρ = 0.344; P = 0.043), but not depression (P = 0.197). There was a significant correlation between tolerability and age (ρ = −0.491; P = 0.003) and disease duration (ρ = −0.442; P = 0.008), but not UPDRS-III scores (P = 0.284). Conclusion Our results have shown limited tolerability of the full neuropsychological battery as outlined by the CAPSIT-PD protocol. We suggest the consideration of updating the neuropsychological assessment used in the CAPSIT-PD protocol.

Background Executive function and information processing speed deficits occur in fragile X premutation carriers (PMC) with and without fragile X-associated tremor/ataxia syndrome (FXTAS). Gait is negatively impacted by cognitive deficits in many patient populations resulting in increased morbidity and falls but these relationships have not been studied in FXTAS. Research question We sought to investigate the associations between executive function and information processing speed and gait, turning and falls in PMC with and without FXTAS compared to healthy controls. Methods Global cognition and the cognitive domains of information processing speed, attention, response inhibition, working memory and verbal fluency were tested with a neuropsychological test battery in 18 PMC with FXTAS, 15 PMC without FXTAS, and 27 controls. An inertial sensor based instrumented Timed Up and Go was employed to test gait, turns and functional mobility. Results Lower information processing speed was significantly associated with shorter stride length, reflecting slower gait speed, in PMC with FXTAS (p = 0.0006) but not PMC without FXTAS or controls. Lower response inhibition was also significantly associated with slower turn-to-sit times in PMC with FXTAS (p = 0.034) but not in those without FXTAS or controls. Lower information processing speed (p = 0.012) and working memory (p = 0.004), were significantly correlated with a greater number of self-reported falls in the past year in FXTAS participants. Significance This is the first study demonstrating that worse executive function and slower information processing speed is associated with reduced gait speed and functional mobility, as well as with a higher retrospective fall history in participants with FXTAS. This information may be important in the design of cognitive and motor interventions for this neurodegenerative disorder.

Author(s): Srivatsal, S; Cholerton, B; Leverenz, JB; Wszolek, ZK; Uitti, RJ; Dickson, DW; Weintraub, D; Trojanowski, JQ; Van Deerlin, VM; Quinn, JF; Chung, KA; Peterson, AL; Factor, SA; Wood-Siverio, C; Goldman, JG; Stebbins, GT; Bernard, B; Ritz, B; Rausch, R; Espay, AJ; Revilla, FJ; Devoto, J; Rosenthal, LS; Dawson, TM; Albert, MS; Mata, IF; Hu, SC; Montine, KS; Johnson, C; Montine, TJ; Edwards, KL; Zhang, J; Zabetian, CP | Abstract: Background: Increasing evidence suggests that genetic factors play a role in the variability associated with cognitive performance in Parkinson's disease (PD). Mutations in the LRRK2 gene are the most common cause of monogenic PD; however, the cognitive profile of LRRK2-related PD is not well-characterized. Methods: A cohort of 1,447 PD patients enrolled in the PD Cognitive Genetics Consortium was screened for LRRK2 mutations and completed detailed cognitive testing. Associations between mutation carrier status and cognitive test scores were assessed using linear regression models. Results: LRRK2 mutation carriers (n=29) demonstrated better performance on the Mini Mental State Examination (P=0.03) and the Letter-Number Sequencing Test (P=0.005). A smaller proportion of LRRK2 carriers were demented (P=0.03). Conclusions: Our cross-sectional study demonstrates better performance on certain cognitive tests, as well as lower rates of dementia in LRRK2-related PD. Future longitudinal studies are needed to determine whether LRRK2 mutation carriers exhibit slower cognitive decline.

Two methods for estimating premorbid IQ were employed in a sample of 199 dementia patients and 26 control subjects: (1) the National Adult Reading Test (NART), a present ability measure, and (2) an age, sex, race, education and occupation regression formula-a demographically based estimate. The dementia sample consisted of probable Alzheimer's disease, multi-inf arct dementia and a mixture of the two. Controls consisted of the spouses of the patient sample. The patient sample was divided into three levels of dementia severity equated for age and level of education. The NART estimates in the mild and moderate/severe dementia groups differed significantly from those for the very mildly demented patients and controls. The results suggest that the applicability of the NART in estimating premorbid IQ in dementia may be limited.

Two methods were used to estimate premorbid IQ in a sample of 68 patients with mild dementia: (1) the National Adult Reading Test (NART), a present ability measure, and (2) an age, sex, race, education and occupation regression formula, a demographically based estimate (DIQ). The dementia sample consisted of probable Alzheimer's disease, multi-infarct dementia and a mixture of the two. The sample was divided into three levels of language disturbances (no language disturbance, naming or fluency disturbance, or both naming and fluency disturbance) based upon performance on the Visual Naming test and the Controlled Oral Word Association test. The NART IQ estimates in patients with one or more language disturbances were significantly lower than those in patients without language disturbances despite equivalent DIQ and Mini-Mental Status exam performance. The results suggest that the applicability of the NART to dementia patients with prominent language disturbances is limited.

Objective:To investigate atrophy of the corpus callosum on MRI in Parkinson disease (PD) and its relationship to cognitive impairment.Methods:One hundred patients with PD and 24 healthy control participants underwent clinical and neuropsychological evaluations and structural MRI brain scans. Participants with PD were classified as cognitively normal (PD-NC; n = 28), having mild cognitive impairment (PD-MCI; n = 47), or having dementia (PDD; n = 25) by Movement Disorder Society criteria. Cognitive domain (attention/working memory, executive function, memory, language, visuospatial function) z scores were calculated. With the use of FreeSurfer image processing, volumes for total corpus callosum and its subsections (anterior, midanterior, central, midposterior, posterior) were computed and normalized by total intracranial volume. Callosal volumes were compared between participants with PD and controls and among PD cognitive groups, covarying for age, sex, and PD duration and with multiple comparison corrections. Regression analyses were performed to evaluate relationships between callosal volumes and performance in cognitive domains.Results:Participants with PD had reduced corpus callosum volumes in midanterior and central regions compared to healthy controls. Participants with PDD demonstrated decreased callosal volumes involving multiple subsections spanning anterior to posterior compared to participants with PD-MCI and PD-NC. Regional callosal atrophy predicted cognitive domain performance such that central volumes were associated with the attention/working memory domain; midposterior volumes with executive function, language, and memory domains; and posterior volumes with memory and visuospatial domains.Conclusions:Notable volume loss occurs in the corpus callosum in PD, with specific neuroanatomic distributions in PDD and relationships of regional atrophy to different cognitive domains. Callosal volume loss may contribute to clinical manifestations of PD cognitive impairment.

The objective of our study was to compare Movement Disorder Society Task Force criteria for diagnosis of Parkinson's disease dementia (PDD) with the gold standard of traditional neuropsychological testing. A short checklist (Level I) and a protocol of neuropsychological tests (Level II) have been proposed by a Movement Disorder Society Task Force but not fully validated in clinical practice. Ninety-one Parkinson's disease (PD) subjects were categorized as having dementia or no dementia based on a battery of neuropsychological test results and clinical judgment. The isolated components needed for Level I and Level II diagnoses were then culled from the neuropsychological evaluations and independently used to designate PDD. Compared with traditional neuropsychological testing, the sensitivity and specificity of Level I criteria for PDD was 66.7% and 98.8%, and for Level II criteria 100% and 92.7%, respectively. Using Level II criteria, 6 additional subjects were diagnosed with PDD that were classified as having no dementia when full neuropsychological data were used for the diagnosis. These 6 subjects had more education years and were less impaired on cognitive tests. The Movement Disorder Society's Level II criteria more frequently classify subjects with PDD than does traditional neuropsychological testing. Whereas Level II criteria may overclassify subjects as having PDD, they are very accurate in ruling out dementia. Movement Disorder Society's criteria are practical and timesaving, although full neuropsychological testing may still be needed. © 2014 International Parkinson and Movement Disorder Society

Visual hallucinations are frequent, disabling complications of advanced Parkinson's disease, but their neuroanatomical basis is incompletely understood. Previous structural brain magnetic resonance imaging studies suggest volume loss in the mesial temporal lobe and limbic regions in subjects with Parkinson's disease with visual hallucinations, relative to those without visual hallucinations. However, these studies have not always controlled for the presence of cognitive impairment or dementia, which are common co-morbidities of hallucinations in Parkinson's disease and whose neuroanatomical substrates may involve mesial temporal lobe and limbic regions. Therefore, we used structural magnetic resonance imaging to examine grey matter atrophy patterns associated with visual hallucinations, comparing Parkinson's disease hallucinators to Parkinson's disease non-hallucinators of comparable cognitive function. We studied 50 subjects with Parkinson's disease: 25 classified as current and chronic visual hallucinators and 25 as non-hallucinators, who were matched for cognitive status (demented or non-demented) and age (± 3 years). Subjects underwent (i) clinical evaluations; and (ii) brain MRI scans analysed using whole-brain voxel-based morphometry techniques. Clinically, the Parkinson's disease hallucinators did not differ in their cognitive classification or performance in any of the five assessed cognitive domains, compared with the non-hallucinators. The Parkinson's disease groups also did not differ significantly in age, motor severity, medication use or duration of disease. On imaging analyses, the hallucinators, all of whom experienced visual hallucinations, exhibited grey matter atrophy with significant voxel-wise differences in the cuneus, lingual and fusiform gyri, middle occipital lobe, inferior parietal lobule, and also cingulate, paracentral, and precentral gyri, compared with the non-hallucinators. Grey matter atrophy in the hallucinators occurred predominantly in brain regions responsible for processing visuoperceptual information including the ventral 'what' and dorsal 'where' pathways, which are important in object and facial recognition and identification of spatial locations of objects, respectively. Furthermore, the structural brain changes seen on magnetic resonance imaging occurred independently of cognitive function and age. Our findings suggest that when hallucinators and non-hallucinators are similar in their cognitive performance, the neural networks involving visuoperceptual pathways, rather than the mesial temporal lobe regions, distinctively contribute to the pathophysiology of visual hallucinations and may explain their predominantly visual nature in Parkinson's disease. Identification of distinct structural MRI differences associated with hallucinations in Parkinson's disease may permit earlier detection of at-risk patients and ultimately, development of therapies specifically targeting hallucinations and visuoperceptive functions.

The recently proposed Movement Disorder Society (MDS) Task Force diagnostic criteria for mild cognitive impairment in Parkinson's disease (PD-MCI) represent a first step toward a uniform definition of PD-MCI across multiple clinical and research settings. However, several questions regarding specific criteria remain unanswered, including optimal cutoff scores by which to define impairment on neuropsychological tests. Seventy-six non-demented PD patients underwent comprehensive neuropsychological assessment and were classified as PD-MCI or PD with normal cognition (PD-NC). The concordance of PD-MCI diagnosis by MDS Task Force Level II criteria (comprehensive assessment), using a range of standard deviation (SD) cutoff scores, was compared with our consensus diagnosis of PD-MCI or PD-NC. Sensitivity, specificity, and positive and negative predictive values were examined for each cutoff score. PD-MCI subtype classification and distribution of cognitive domains impaired were evaluated. Concordance for PD-MCI diagnosis was greatest for defining impairment on neuropsychological tests using a 2 SD cutoff score below appropriate norms. This cutoff also provided the best discriminatory properties for separating PD-MCI from PD-NC compared with other cutoff scores. With the MDS PD-MCI criteria, multiple domain impairment was more frequent than single domain impairment, with predominant executive function, memory, and visuospatial function deficits. Application of the MDS Task Force PD-MCI Level II diagnostic criteria demonstrates good sensitivity and specificity at a 2 SD cutoff score. The predominance of multiple domain impairment in PD-MCI with the Level II criteria suggests not only influences of testing abnormality requirements, but also the widespread nature of cognitive deficits within PD-MCI.

Importance Parkinson disease (PD) is heterogeneous in symptom manifestation and rate of progression. Identifying factors that influence disease progression could provide mechanistic insight, improve prognostic accuracy, and elucidate novel therapeutic targets. Objective To determine whether GBA mutations and the E326K polymorphism modify PD symptom progression. Design, Setting, and Participants The entire GBA coding region was screened for mutations and E326K in 740 patients with PD enrolled at 7 sites from the PD Cognitive Genetics Consortium. Detailed longitudinal motor and cognitive assessments were performed with patients in the on state. Main Outcomes and Measures Linear regression was used to test for an association between GBA genotype and motor progression, with the Movement Disorder Society–sponsored version of the Unified Parkinson’s Disease Rating Scale Part III (MDS-UPDRS III) score at the last assessment as the outcome and GBA genotype as the independent variable, with adjustment for levodopa equivalent dose, sex, age, disease duration, MDS-UPDRS III score at the first assessment, duration of follow-up, and site. Similar methods were used to examine the association between genotype and tremor and postural instability and gait difficulty (PIGD) scores. To examine the effect of GBA genotype on cognitive progression, patients were classified into those with conversion to mild cognitive impairment or dementia during the study (progression) and those without progression. The association between GBA genotype and progression status was then tested using logistic regression, adjusting for sex, age, disease duration, duration of follow-up, years of education, and site. Results Of the total sample of 733 patients who underwent successful genotyping, 226 (30.8%) were women and 507 (69.2%) were men (mean [SD] age, 68.1 [8.8] years). The mean (SD) duration of follow-up was 3.0 (1.7) years. GBA mutations (β = 4.65; 95% CI, 1.72-7.58; P = .002), E326K (β = 3.42; 95% CI, 0.66-6.17; P = .02), and GBA variants combined as a single group (β = 4.01; 95% CI, 1.95-6.07; P = 1.5 × 10 −4 ) were associated with a more rapid decline in MDS-UPDRS III score. Combined GBA variants (β = 0.38; 95% CI, 0.23-0.53; P = .01) and E326K (β = 0.64; 95% CI, 0.43-0.86; P = .002) were associated with faster progression in PIGD scores, but not in tremor scores. A significantly higher proportion of E326K carriers (10 of 21 [47.6%]; P = .01) and GBA variant carriers (15 of 39 [38.5%]; P = .04) progressed to mild cognitive impairment or dementia. Conclusions and Relevance GBA variants predict a more rapid progression of cognitive dysfunction and motor symptoms in patients with PD, with a greater effect on PIGD than tremor. Thus, GBA variants influence the heterogeneity in symptom progression observed in PD.

Mild cognitive impairment is increasingly recognized as a construct in Parkinson's disease (PD) and occurs in about 25% of nondemented PD patients. Although executive dysfunction is the most frequent type of cognitive deficit in PD, the cognitive phenotype of PD mild cognitive impairment (PD-MCI) is broad. PD-MCI subtypes are represented by amnestic and nonamnestic domain impairment as well as single- and multiple-domain impairment. However, it is unclear whether patients with different PD-MCI subtypes also differ in other clinical characteristics in addition to cognitive profile. We studied 128 PD-MCI subjects at our Movement Disorders center, comparing clinical, motor, and behavioral characteristics across the PD-MCI subtypes. We found varying proportions of impairment subtypes: nonamnestic single domain, 47.7%; amnestic multiple domain, 24.2%; amnestic single domain, 18.8%; and nonamnestic multiple domain, 9.5%. Attentional/executive functioning and visuospatial abilities were the most frequently impaired domains. PD-MCI subtypes differed in their motor features, with nonamnestic multiple-domain PD-MCI subjects showing particularly pronounced problems with postural instability and gait. Differences among PD-MCI subtypes in age, PD duration, medication use, mood or behavioral disturbances, and vascular disease were not significant. Thus, in addition to differing cognitive profiles, PD-MCI subtypes differed in motor phenotype and severity but not in mood, behavioral, or vascular comorbidities. Greater postural instability and gait disturbances in the nonamnestic multiple-domain subtype emphasize shared nondopaminergic neural substrates of gait and cognition in PD. Furthermore, increased burden of cognitive dysfunction, rather than type of cognitive deficit, may be associated with greater motor impairment in PD-MCI.

Volumetric measures of mesial temporal lobe structures on MRI scans recently have been explored as potential biomarkers of dementia in patients with PD, with investigations primarily focused on hippocampal volume. Both in vivo MRI and postmortem tissue studies in Alzheimer's disease, however, demonstrate that the entorhinal cortex (ERC) is involved earlier in disease-related pathology than the hippocampus. The ERC, a region integral in declarative memory function, projects multimodal sensory information to the hippocampus through the perforant path. In PD, ERC atrophy, as measured on MRI, however, has received less attention, compared to hippocampal atrophy. We compared ERC and hippocampal atrophy in 12 subjects with PD dementia including memory impairment, 14 PD subjects with normal cognition, and 14 healthy controls with normal cognition using manual segmentation methods on MRI scans. Though hippocampal volumes were similar in the two PD cognitive groups, ERC volumes were substantially smaller in the demented PD subjects, compared to cognitively normal PD subjects (P < 0.05). In addition, normalized ERC and hippocampal volumes for right and left hemispheres were significantly lower in the demented PD group, compared to healthy controls. Our findings suggest that ERC atrophy differentiates demented and cognitively normal PD subjects, in contrast to hippocampal atrophy. Thus, ERC atrophy on MRI may be a potential biomarker for dementia in PD, particularly in the setting of memory impairment.

The objective of this work was to evaluate the Movement Disorders Society (MDS) Task Force-proposed screening checklist for detecting Parkinson's disease dementia (PD-D) in relation to full neuropsychological testing. An MDS Task Force has proposed diagnostic procedures for PD-D, which have not been fully validated against more extensive neuropsychological testing. PD subjects were recruited from 2 specialty centers. A neuropsychologist evaluated them for dementia as part of routine clinical care. Independent clinical neurologists administered the MDS PD-D screening checklist. Diagnosis of PD-D by the 2 methods was compared. Ninety-one PD subjects had a mean age of 66.3 (SD = 9.7) years and a mean PD duration of 8.8 (SD = 6.1) years. Seven subjects (7.7%) met all 8 screening checklist criteria from the MDS PD-D screening tool and were classified as probable PD-D. Fifteen (16.5%) subjects were classified as PD-D by full neuropsychological assessment. The screening checklist showed 100% specificity, but only 46.7% sensitivity, for diagnosing PD-D compared to the full neuropsychological assessment. PD-D cases missed by the PD-D screening tool were largely due to 2 checklist items that were not endorsed (absence of depression and Mini-Mental State Examination [MMSE] scores

The objective of this study is to assess the association between tic severity, attention deficit disorder, obsessive-compulsive behavior, and quality of life (QOL) in children with Gilles de la Tourette syndrome (GTS). GTS is a multidimensional disorder with disturbances in motor function and behavior. However, little is known about what variables are associated with QOL in these patients. We evaluated 56 outpatients with a diagnosis of GTS. The mean age was 10 (range 5-17 years). Tics were assessed with the Yale Global Tic Severity Scale (YGTSS). Behavioral scales included the Leyton Obsessional Inventory-Child Version, Children's Yale-Brown Obsessive Compulsive Scale (CY-BOCS), and Attention-Deficit/Hyperactivity Disorder (ADHD) rating scale. The patient's parent also completed the TNO-AZL Children's Quality of Life scale (TACQOL). YGTSS scores ranged from 4 to 30, indicating mild to moderate tic severity. Motor and phonic tic ratings were not correlated with QOL. However, both ADHD and OCD were significantly related to QOL. Subanalysis of ADHD subtypes demonstrated that inattentiveness but not hyperactivity predicted lower QOL. When ADHD, Leyton OCD, and tic severity were considered simultaneously, tic severity remained non-significant, while both ADHD and OCD remained significant contributors to QOL. In summary, in patients with mild to moderate GTS, QOL relates primarily to co-morbidities of ADHD and obsessive-compulsive behavior. ADHD with predominantly inattentive symptoms, rather than hyperactivity symptoms, was associated with lower QOL. To improve QOL, clinicians must consider treatments of co-morbidities among tic patients.

Purpose: Fragile X-associated tremor/ataxia syndrome (FXTAS) was originally defined as tremor, ataxia, cognitive decline, and parkinsonism in individuals who carry between 55 and 200 CGG repeats in the promoter region of the fragile X mental retardation 1 (FMR1) gene. This paper describes a series of patients who meet the definition of FXTAS who presented for care between 2009 and 2014. Methods/Results: Retrospective chart review of patients seen in the FXTAS clinic at Rush University in Chicago. Conclusions: Patients with FXTAS may present with a progressive supranuclear palsy-like phenotype and other eye movement abnormalities are common in these patients as well. Rapid worsening of gait abnormalities in FXTAS may be due to a secondary spinal issue and should be aggressively treated to regain function. Finally, the FXTAS Rating Scale score does not reliably inform the certainty of diagnosis or CGG repeat size in these patients.

The optimal properties of a comprehensive (level II) neuropsychological battery for determining Parkinson's disease mild cognitive impairment (PD-MCI) by Movement Disorder Society (MDS) Task Force criteria remain unresolved.Seventy-six nondemented PD patients underwent PD-MCI classification using a consensus diagnosis and level II criteria. We examined the optimal number of tests in each of the five designated cognitive domains, identified the best tests within each domain, and determined the best overall battery for PD-MCI level II diagnosis.A battery with two tests per domain provided a highly practical, robust diagnostic assessment. Level II testing with the two best tests and impairment defined as 2 standard deviations below norms was highly sensitive and specific for PD-MCI diagnosis.Our findings strongly support the MDS Task Force Level II testing recommendations, provide a framework for creating an optimal, efficient neuropsychological test battery for PD-MCI diagnosis, and offer specific test recommendations.

Objective In subjects with psychogenic movement disorders (PMDs), we conducted a 6 month randomized, cross-over design study to assess the effect of 3 months of psychodynamic psychotherapy followed by observation by the neurologist vs. observation by the neurologist, then 3 months of psychiatric intervention. Background PMDs are often disabling but no uniformly successful treatment strategies have been identified. Short term, open label psychodynamic psychotherapy has been successful in improving PMDs but whether PMDs improve equally well with neurological observation and support has not been tested. Design Fifteen patients with PMDs were randomized to immediate vs. delayed (after 3 months) weekly psychodynamic psychotherapy for 12 weeks. During the phase without psychiatric intervention, they were monitored by the treating neurologist. Patients were assessed at baseline, 3 and 6 months. Change in their movement disorder was assessed using a clinical global impression scale change (CGI-c), depression and anxiety using the Hamilton Depression Scale (HAM-D) and Beck Anxiety Inventory (Beck-A). Results Fourteen women and one man, age 42.3 ± 11, disease duration 63.2 ± 73 months, were randomized to immediate (7 patients) or delayed (8 patients) treatment. Over the six month study, PMDs, depression and anxiety were significantly improved but time was the determinant factor without an independent effect of treatment assignment. Conclusion In this group of PMD patients, where patients were kept within the medical system and involved in a research program, PMDs as well as depression and anxiety improved, but without specific benefit time-linked to psychotherapy as opposed to neurological observation and support.

Cognitive dysfunction is one of the hallmarks of Huntington's disease (HD) and may precede the onset of motor symptoms. The Montreal Cognitive Assessment (MoCA), a brief cognitive screening instrument with high specificity and sensitivity for detecting early cognitive impairments, has not been studied in the HD population. In this study, we compare the MoCA with the mini-mental state examination (MMSE) as a screening tool for cognitive dysfunction among 53 patients with HD. The mean MMSE score was 26 +/- 2.4, and mean MoCA score was 21 +/- 4.4. Twenty-one patients (81%) of those who scoredor=26 on the MMSE had the MoCA score26. Thirty-two patients (78%) of those who scoredor=24 on the MMSE had the MoCA score24. The MoCA may be a more sensitive screening tool for cognitive impairments in HD relative to the MMSE.

The Mini-Mental State Examination (MMSE) is a commonly used test for screening cognitive impairment and dementia. The questions assess different cognitive areas such as orientation, attention, memory, language, and visuoconstruction. The MMSE is helpful in scaling cognitive impairment, documenting cognitive changes over time, and assessing the effects of therapeutic agents on cognition.

Besides the motor dysfunction, which is a well-known feature of Parkinson's disease (PD), nonmotor features affecting cognition, behavior, and mood are commonly present in PD and troublesome for both patients and caregivers. The neuropsychological assessment forms an important component of the evaluation of these nonmotor features, thereby providing screening or diagnostic tests for clinical care or research, and subsequently, longitudinal assessments of cognitive and behavioral change.

The heterogeneity within vascular dementia has made neuropsychological research in this area difficult to interpret. We studied a subtype of vascular dementia, Binswanger's disease (BD), diagnosed according to recently specified clinical and radiological criteria. Measures of episodic and semantic memory were administered to BD patients, patients with Alzheimer's disease (AD) comparable to the BD sample in dementia severity, age, and education, and normal controls. Episodic memory was more defective in AD than in BD; these patient groups were equally impaired on measures of semantic memory. The findings suggest that assessment of episodic memory may be useful in differentiating AD from BD.

The relationship of behavioral disturbances in Alzheimer's disease to disease severity, age at onset, and the presence of extrapyramidal signs was investigated in three studies. Five categories of behavior disturbance were ascertained through structured interview with the patient's primary caregiver: apathy, agitation, psychotic symptoms, disinhibition, and irritability. In Study 1, measures of disease severity accounted for 42% of the variance in the Apathy scale but less than 20% of the variance in the remaining scales. In Study 2, the presence of extrapyramidal signs was associated with increased Apathy and moderated the association between disease severity and the Psychotic Symptoms and Irritability scales. In Study 3, age at onset was associated with the Agitation scale and moderated the association between disease severity and the Apathy, Psychotic Symptoms, and Irritability scales. The findings are discussed in terms of the clinical heterogeneity within Alzheimer's disease, the possible biological bases of these behavioral disturbances, and the psychometric issues pertinent to their measurement.

This study tested the hypothesis that left versus right deep brain stimulation (DBS) of the subthalamic nucleus (STN) would have differential effects on speech. Twenty right-handed individuals with advanced Parkinson’s disease (PD) underwent unilateral STN DBS. Ten were operated on the right and 10 on the left hemisphere as indicated by severity of nonspeech motor function. Speech was evaluated before surgery and 3 to 6 months after surgery with stimulator-off and with stimulator-on, with all participants off anti-parkinsonian medication for 12 hours before evaluation. Evaluators and patient speakers were blinded to the stimulator status at the postsurgery evaluations. Motor performance was assessed with UPDRS-III. Each participant produced three samples of diadochokinetic syllables. Syllable rate, syllable and vowel duration, VOT, and F0 were obtained. The diadochokinetic syllables were rated for articulatory accuracy and speaking rate. Twenty graduate clinicians served as judges. The samples were randomly presented via headphones. A mixed ANOVA with repeated measures was used to assess the significance of the changes in UPRS-III scores and speech measures. The results indicated that unilateral STN DBS produced improvement in nonspeech motor function regardless of the side of stimulation. In contrast, the changes in articulatory accuracy and syllable rate associated with the STN DBS were hemisphere specific.

Background PMD are disabling, but lack any generally accepted treatment strategies. Design/methods Ten patients with PMD received treatment with Psychodynamic Psychotherapy. Patients were assessed with psychiatric rating scales and the movement disorder was rated by a blinded rater with the Psychogenic Movement Disorder Rating Scale (PMDRS). Results Total mean PMDRS ( p =0.0195), total PMDRS function scores ( p =0.0142), Hamilton depression scores ( p =0.009), Beck anxiety scores ( p =0.002), and GAF ( p =0.0083) all improved with psychotherapeutic intervention. Conclusions Psychotherapy and appropriate use of adjunct psychiatric medication can be a successful intervention for PMD.

This paper reports findings on the respiratory/phonatory subsystems from an on-going study investigating the effect of unilateral electrostimulation of the subthalamic nucleus (STN) on different speech subsystems in people with Parkinson's disease (PD). Speech recordings were made in the medication-off state at baseline, three months post surgery with stimulation-on, and with stimulation-off, in six right-handed PD patients. Subjects completed several speech tasks. Acoustic analyses of the maximally sustained vowel phonation were reported. The results were compared to the scores of the motor section of the Unified Parkinson's Disease Rating Scale (UPDRS-III) obtained under the same conditions. Results showed that stimulation-on improved UPDRS-III scores in all six subjects. While mild improvement was observed for all subjects in the Stimulation-on condition, three subjects received left-STN stimulation showed a significant decline in vocal intensity and vowel duration from their baseline indicating the speech function was very susceptible to micro lesions due to the surgical procedure itself when the surgical site was in the dominant hemisphere.

BACKGROUND: Previous studies have suggested that the risk of injury is elevated among persons with dementia, but these studies have focused primarily on falls and fractures. This study characterizes all injuries incurred in a large sample of community-dwelling persons with a specific form of dementia, Alzheimer's disease (AD). SUBJECTS AND METHODS: The sample consisted of 281 community-dwelling persons diagnosed with AD according to NINCDS/ADRDA guidelines. Information regarding all injuries occurring within the previous 6 months was obtained through a structured interview of a caregiver. RESULTS: The rate of injuries was 58.4 per 100 persons per year. Although falling was the single most common mechanism by which injuries occurred, it accounted for only 43.8% of all injuries. Fractures accounted for 13.7% of injuries. Medical treatment was sought for 52.1% of the injuries. After adjustment for age and gender, the likelihood of injury was significantly associated with cognitive impairment and with ADL limitation, but the independent contribution of these two factors could not be assessed. CONCLUSIONS: The findings suggest that injuries are a significant problem in persons with AD

Objective: To compare diagnostic classification differences for Parkinson9s disease dementia (PDD) patients between the new Movement Disorder Society (MDS) criteria for detecting PDD and routine neuropsychological testing. Background Diagnostic criteria for PDD have been proposed by a MDS Task Force. MDS PDD diagnosis includes criteria based on a checklist (Level 1) and additional specific criteria based on more complete neuropsychological tests (Level II). Few studies have compared outcomes of these MDS criteria to the diagnosis of PDD based on routine neuropsychological testing that does not utilize the MDS criteria. Design/Methods: Parkinson9s disease (PD) subjects were recruited from those scheduled for neuropsychological testing at two specialty PD centers. All subjects were categorized as having PDD or no PDD based on routine neuropsychological test results and clinical judgment of the neuropsychologist. In addition, Level 1 and Level II MDS diagnostic criteria for PDD were applied to each subject based on the same test results by a blinded neurologist. Results: We tested 91 PD subjects, with mean age 66.3 (SD=9.7). All subjects classified as PDD by the neuropsychologists (n = 9) were also classified as having PDD using the MDS checklist criteria (Level 1). However, there were an additional 6 subjects diagnosed with PDD using the MDS Level II criteria who were classified as having no dementia by the neuropsychologists. These 6 cases had more significantly more education (15.5 vs 10.6 years), better MMSE scores (26.33 vs 20.4), and less impairment on several cognitive tests compared to the group concordant for PDD by both MDS criteria and the neuropsychologist designation. Conclusions: MDS Level II criteria diagnoses PDD more frequently compared to routine neuropsychological testing and may be more sensitive to impairment in cases with higher education levels and where the cognitive function is not as severely impaired. Supported by: Salary support for the Rush University Medical Center study participants was provided by the Parkinson9s Disease Foundation. Disclosure: Dr. Barton has received personal compensation for activities with Teva Neurosciences, Allergan, Inc., Merz Pharma, Lundbeck Research USA, Inc., Merck-Serono, IMPAX, Allergan and Parkinson Disease Foundation. Dr. Bernard has nothing to disclose. Dr. Stebbins has received personal compensation for activities with Impax Laboratories, Inc., Ceregene, Inc., Biovail Technologies, Ltd., Santhera Pharmaceuticals, and Ingenix Pharmaceutical Services. Dr. Stebbins has received research support from the National Institutes of Health, American Cancer Society, the Michael J. Fox Foundation, and Fragile-X Foundation. Dr. Goldman has received personal compensation for activities with Movement Disorder Society, American Geriatric Society, Johns Hopkins Dystonia and Spasticity Practicum as a speaker. Dr. Goldman has received research support from the Parkinson9s Disease Foundation and the National Institute of Health. Dr. Dubois has received personal compensation for activities with Bristol-Myers Squibb, Roche, Elan, Eli Lilly, Eisai, and Janssen as a consultantDr. Dubois has received personal compensation for serving on the advisory board of Bristol-Myers Squibb, Roche, Elan, Eli Lilly, Eisai, and Janssen.Dr. Dubois has received research support from Novartis and Sanofi-Aventis. Dr. Goetz has received personal compensation for activities with Asubio Pharmaceuticals Inc., Campbell Alliance, CNS Therapeutics, Curry Rockerfeller Group, Health Advances, Impax Pharmaceuticals, Ingenix, Juvantia Pharma LTD as a consultant and participant on an advisory board. Dr. Goetz has received personal compensation in an editorial capacity for Movement Disorders and Oxford University Press. Dr. Goetz has received research support from Michael J. Fox Foundation, National Institute of Health and Parkinson9s Disease Foundation.

Objective: To assess cognitive functioning in patients with Parkinson9s disease (PD) following unilateral and subsequent contralateral deep brain stimulation of the subthalamic nucleus (STN-DBS). Background Bilateral STN-DBS is associated with mild decline in executive functioning. Staged surgery may be able to reduce such changes. However, there is little research on the cognitive effects of staged surgery. The present study examined cognitive functioning in PD patients before and after unilateral and subsequent contralateral STN-DBS. Design/Methods: We evaluated 16 consecutive PD patients (9 men, 7 women; mean age 67.4 ± 9.9) with the Mattis Dementia Rating Scale (MDRS), Rey Auditory and Verbal Learning Test (RAVLT), Controlled Oral Word Association (COWA; FAS), Digit Ordering Test, Symbol Digit Modalities Test (SDMT), Raven9s Progressive Matrices (modified), and Montgomery and Asberg Depression Rating Scale. Subjects were evaluated before the first surgery, about 8 months after the first surgery, and about 3.5 years after the second surgery. Differences between baseline and follow-up were assessed with repeated measures ANOVA. Results: Mean MDRS total score declined from 136.4 ± 2.0 at baseline, to 134.8 ± 2.4 after the first surgery, and to 129.5 ± 4.0 after the second surgery (p=0.02). Of the MDRS subscales, Initiation/Perseveration was the only scale to decline over time (p=0.02). There was decline for both letter fluency (p=0.0005) and category fluency (p=0.003). The SDMT raw score also showed decline (p=0.005). There were no significant changes for Digit Ordering Test, delayed memory, conceptual reasoning, or depression. Conclusions: Staged STN-DBS is associated with mild decline in overall level of functioning, fluency, and some aspects of executive functioning, similar to simultaneous bilateral surgery. However, since the second follow-up assessment occurred approximately 6 years after the baseline assessment, the observed decline may not be different from the natural progression of the disease. These results suggest that staged STN-DBS does not reduce frontal/striatal executive changes. Disclosure: Dr. Bernard has nothing to disclose. Dr. Stebbins has received personal compensation for activities with Impax Laboratories, Inc., Ceregene, Inc., Biovail Technologies, Ltd., Santhera Pharmaceuticals, and Ingenix Pharmaceutical Services. Dr. Stebbins has received research support from the National Institutes of Health, American Cancer Society, the Michael J. Fox Foundation, and Fragile-X Foundation. Dr. Bakay has received personal compensation for activities with Bayer/Schering for serving on their Safety Monitoring Board. Dr. Bakay has received research support from Ceregene, Inc., Medtronic, ANS and NIH. Dr. Verhagen has received personal compensation for activities with Medtronic, Inc., and Impax. Dr. Verhagen has received research support from Medtronic, Inc., ANS/St. Jude, Ceregene, Impax, Bayer-Schering, National Institutes of Health, and the Michael J Fox Foundation.

The study reports the effect of subthalamic deep brain stimulation (STN DBS) on vocal function in Parkinson’s disease (PD). Specifically, the effect was evaluated in relation to the vibratory characteristics of the vocal folds during sustained vowel phonation using two different methods: one measures jitter and shimmer, while the other measures the correlation dimension D2, a nonlinear dynamic analysis. Twenty right‐handed individuals with advanced PD and dysarthria underwent unilateral STN DBS. Ten were operated on the right hemisphere and ten on the left hemisphere. The side receiving STN DBS had more affected motor function. Speech was evaluated before surgery and three‐to‐six months after surgery with stimulator‐off and with stimulator‐on; all were off anti‐Parkinsonian medication for 12 h before evaluation. Evaluators and subjects were blinded to the subjects stimulator status at the postsurgery evaluations. Nonspeech motor performance was assessed with UPDRS‐III. Each subject produced six maximally ...

Previously, it was found that 16 right‐handed patients with idiopathic Parkinsons disease who underwent unilateral implantation of deep brain stimulator in subthalamic nucleus (STN) showed significant improvement in their nonspeech motor functions. Eight of the 16 patients had stimulator in the left STN and eight in the right STN. In contrast, their speech function showed very mild improvement that was limited to the respiratory/phonotory subsystems. Further, there seemed a trend that the patients with right STN stimulation did better than those with left STN stimulation. It was speculated that the difference might be due to a micro lesion caused by the surgical procedure to the corticobulbar fibers run in the left internal capsule. This paper reports speech changes associated with bilateral DBS in STN in four of the 16 subjects who elected to have deep brain stimulator implanted in STN on the opposite side of the brain at a later time. Results show negative changes in speech after bilateral DBS in STN. T...

We surveyed 522 consecutive patients from a dementia clinic to assess duration of driving after disease onset and instances of unsafe motor vehicle operation in the preceding 6 months. Among the 333 patients licensed to drive at the onset of dementia, the median duration of driving after onset was 28.6 months. Patients with a clinical diagnosis of Alzheimer's disease drove significantly longer than those with other dementia syndromes. Of the 93 patients still driving at the time of the survey, approximately one third were reported to have had at least one form of unsafe motor vehicle operation in the past 6 months, including 21 patients with motor vehicle accidents. Motor vehicle accidents were associated with use of prescription medications with sedative properties and with lower subjective ratings of the patient's driving ability by the informant. ( Arch Intern Med . 1991;151:941-946)