Jeffrey Wilken

Decrements in vigilance and cognitive functioning associated with ragweed-induced allergic rhinitis

BACKGROUND AND OBJECTIVE The adverse effects of untreated seasonal allergic rhinitis (AR) on performance in the workplace, school, and home are poorly understood. To delineate more clearly the impact and consequences of the disease on performance, the effect of symptomatic AR on vigilance and a wide range of cognitive functions was investigated. METHODS A battery of automated neuropsychological tests was administered to asymptomatic adult subjects with histories of AR. Subjects were randomized to either a symptomatic or to an asymptomatic group. Subjects in the symptomatic group were exposed to ragweed pollen in a controlled exposure setting until they demonstrated predetermined severities of AR symptoms. Subjects in the asymptomatic group were not exposed to ragweed pollen in the environmental unit and retained a minimum symptom profile. The battery of cognitive measures was re-administered to both groups. RESULTS AR had major adverse impacts on measures of vigilance. Further, AR adversely affected a broad range of cognitive functions. Specifically, subjects with AR symptoms demonstrated longer response times and decreased efficiency on measures of working memory, psychomotor speed, reasoning/computation, and divided attention as compared with asymptomatic subjects. CONCLUSIONS In addition to decreased vigilance, AR was associated with decrements in speed and efficiency across several cognitive domains. This is similar to findings in research on medications and medical conditions that cause sedation. Findings may represent a link between AR and poor productivity/personal safety among AR sufferers. This suggests that these results have implications with regard to public health.

A comparison of the effect of diphenhydramine and desloratadine on vigilance and cognitive function during treatment of ragweed-induced allergic rhinitis

BACKGROUND Decrements in cognitive performance are associated with the use of sedating antihistamines. Most, but not all, second-generation antihistamines have been found to be nonsedating. OBJECTIVE To examine the central nervous system (CNS) profile of a new second-generation antihistamine, desloratadine. METHODS Subjects with ragweed-induced allergic rhinitis (aged 18-60 years) who demonstrated a predetermined severity of symptoms after priming with ragweed pollen in the Environmental Exposure Unit were randomized to receive a single dose of desloratadine, 5 mg; diphenhydramine, 50 mg; or placebo. A comprehensive battery of repeatable, automated neuropsychological tests was administered to subjects before treatment (symptomatic baseline) and 90 minutes after taking study medication. RESULTS Both desloratadine (P = .04) and diphenhydramine (P < .01) alleviated the symptoms of allergic rhinitis compared with placebo, but treatment with diphenhydramine was associated with clinically meaningful decrements on all vigilance parameters (P < .05 for desloratadine-diphenhydramine contrasts). Also, subjects treated with diphenhydramine performed significantly worse than subjects given desloratadine or placebo across all cognitive domains evaluated. Most effect sizes for the mean desloratadine and diphenhydramine differences were between 0.4 and 0.8 (moderate to high). Stanford Sleepiness Scale scores also indicated significantly more somnolence with diphenhydramine vs desloratadine or placebo (P < .001). There were no significant differences on any of the cognitive parameters between subjects treated with desloratadine and those given placebo. CONCLUSIONS Desloratadine improved ragweed-induced allergic rhinitis symptoms without adversely affecting performance. Diphenhydramine improved allergic rhinitis symptoms but caused significant decrements in vigilance and cognitive functioning. Thus, efficacy of antihistamine treatment must be balanced against the associated effects on CNS functioning.

Cognitive dysfunction in multiple sclerosis: Assessment, imaging, and risk factors.

Up to 70% of multiple sclerosis (MS) patients experience cognitive dysfunction during the course of their disease. The most often affected domains are attention, memory, and information processing speed. Sequelae of cognitive dysfunction include negative effects on activities of daily living, employment, and relationships. This article reviews cognitive dysfunction in MS and focuses specifically on assessment, imaging, and risk factors. A number of neuropsychological batteries have been developed specifically for assessing cognitive dysfunction in MS patients. Trade-offs in length, administrative support, and efficiency exist between the various batteries. Modern imaging techniques provide a clearer picture of MS-related damage to the central nervous system, which is the major cause of cognitive dysfunction. Additionally, candidate risk factors have been identified that may help predict which patients will develop cognitive dysfunction.

Changes in Fatigue and Cognition in Patients with Relapsing Forms of Multiple Sclerosis Treated with Natalizumab: The ENER-G Study

Fatigue and cognitive impairment are debilitating features of multiple sclerosis (MS). ENER-G was a 12-month, open-label, multicenter, single-arm observational study designed to evaluate changes in fatigue and cognition in MS patients treated with natalizumab. Adults with relapsing MS and initiating natalizumab were enrolled. The primary endpoint was change in Visual Analog Scale for Fatigue (VAS-F) score over 12 weeks. Changes in Modified Fatigue Impact Scale (MFIS) score, Fatigue Severity Scale (FSS) score, and cognitive performance, using Automated Neuropsychological Assessment Metrics (ANAM), were also assessed. Patients (N = 89) had a mean age of 41 years and a median Expanded Disability Status Scale score of 3.0, and 83% had used at least two prior MS therapies. Significant improvements were observed and maintained at 12 weeks in VAS-F (mean ± SD baseline score, 77.7 ± 10.2; mean ± SD change, -14.9 ± 17.1; P < .0001), MFIS (mean baseline score, 59.1 ± 12.2; mean change, -7.4 ± 11.8; P < .0001), and FSS (median baseline score, 6.3 [range, 3.9-7.0]; median change, -0.4 [range, -2.9-1.4]; P < .0001). Cognitive performance remained stable or improved (depending on the ANAM measure). Thus significant improvements in fatigue were maintained over time, and cognitive performance improved or remained stable up to 48 weeks after initiation of natalizumab in MS patients with some degree of fatigue.

Cognitive Changes and Quality of Life in Neurocysticercosis: A Longitudinal Study

Background Few studies have focused on the cognitive morbidity of neurocysticercosis (NCC), one of the most common parasitic infections of the central nervous system. We longitudinally assessed the cognitive status and quality of life (QoL) of patients with incident symptomatic NCC cases and matched controls. Methodology/Principal Findings The setting of the study was the Sabogal Hospital and Cysticercosis Unit, Department of Transmissible Diseases, National Institute of Neurological Sciences, Lima, Peru. The design was a longitudinal study of new onset NCC cases and controls. Participants included a total of 14 patients with recently diagnosed NCC along with 14 healthy neighborhood controls and 7 recently diagnosed epilepsy controls. A standardized neuropsychological battery was performed at baseline and at 6 months on NCC cases and controls. A brain MRI was performed in patients with NCC at baseline and 6 months. Neuropsychological results were compared between NCC cases and controls at both time points. At baseline, patients with NCC had lower scores on attention tasks (p<0.04) compared with epilepsy controls but no significant differences compared to healthy controls. Six months after receiving anti-parasitic treatment, the NCC group significantly improved on tasks involving psychomotor speed (p<0.02). QoL at baseline suggested impaired mental function and social function in both the NCC and epilepsy group compared with healthy controls. QoL gains in social function (p = 0.006) were noted at 6 months in patients with NCC. Conclusions/Significance Newly diagnosed patients with NCC in this sample had mild cognitive deficits and more marked decreases in quality of life at baseline compared with controls. Improvements were found in both cognitive status and quality of life in patients with NCC after treatment.

Recognizing and treating common psychiatric disorders in multiple sclerosis.

Background:The rate of depression and other psychiatric disorders is greater in multiple sclerosis (MS) than in other chronic conditions or neurologic diseases. This means that clinical neurologists seeing MS patients will frequently be engaged in the diagnosis and treatment of psychiatric distress. Review Summary:This review provides a summary of what is known about psychiatric dysfunction in MS. It offers information about the current views on the link between various psychiatric disorders and MS. More important, it offers suggestions on how the knowledge from existing research can be integrated into real-world practice. Conclusion:Clinicians need to understand the factors that influence the development of psychiatric disorders in MS, the relationship between disease-modifying therapies and psychiatric distress, and the issues surrounding the treatment of psychiatric conditions in MS. Thorough knowledge of psychiatric dysfunction and MS will allow the clinician to design an effective treatment regimen that helps patients cope with their disease.

Reliability of a cognitive endpoint for use in a multiple sclerosis pharmaceutical trial

OBJECTIVE Determine reliability and basic psychometric properties of a composite cognitive endpoint, MS-COG, for monitoring change in cognitive function in MS drug trials. BACKGROUND 50% of MS patients have cognitive impairment that impacts ability to work and quality of life. We selected neuropsychological tests based on sensitivity to MS cognitive impairment, availability of alternate forms, cross-cultural utility, and feasibility for multicenter trials, and assessed the reliability and validity of a composite endpoint, MS-COG. DESIGN/METHODS Administered SRT, BVMT-R, PASAT, and SDMT to 60 MS patients at 4 US centers twice over 45days, along with symptom inventories by patients and informants. RESULTS The MS-COG had test-retest reliability of 0.91. Processing Speed and Memory indices had reliabilities of 0.89 and 0.86, with modest practice effects. Reliability was high for the RR MS and SP MS subgroups as well, with correlations of .90 and .93, respectively for MS-COG. Overall, 42% of subjects obtained MS-COG scores in the impaired range, with SP MS subjects performing 0.8 SD below RR MS subjects. Impairment correlated well (r=0.37 to 0.40) with informant reports but was inconsistent with patient report, with the least reliable assessments by those with greater symptom severity. CONCLUSIONS The MS-COG is a reliable, repeatable measure of MS cognitive functioning that is sensitive to cognitive impairment in SP MS and RR MS patients and feasible for multicenter clinical trials. Further development is warranted.

Treatment of Multiple Sclerosis–Related Cognitive Problems With Adjunctive Modafinil: Rationale and Preliminary Supportive Data

In patients with multiple sclerosis (MS), attention and information-processing-speed impairment contribute to dysfunction in other cognitive domains (learning, memory). Treatment for MS-related attention and processing-speed deficits may have dual benefits: improvement of function in these domains and in overall cognitive efficiency. The objective of this study was to determine whether adjunctive treatment of fatigue with modafinil ameliorates deficits in attention and cognitive domains reliant on attention. Relapsing-remitting MS patients receiving intramuscular interferon beta-1a (IM IFNβ-1a) were screened for attention problems with four well-validated, reliable, standardized neurocognitive measures sensitive to attention impairment. Those scoring at least 1 standard deviation below normative expectations on at least two of the measures were eligible for continued participation. Participants with normal values on all physical screening measures were randomized to one of two groups: continued IM IFNβ-1a...

Neuropsychologic assessment of a population-based sample of Gulf War veterans.

Objective:The objective of this project was to compare neuropsychologic performance and quality of life in a population-based sample of deployed Gulf War (GW) veterans with and without multisymptom complaints. Background/Methods:The study participants were obtained from the 30,000 member population-based National Health Survey of GW-era veterans conducted in 1995. Cases (N=25) were deployed to the year 1990 and 1991 GW and met Center for Disease Control and Prevention criteria for multisymptom GW illness (GWI). Controls (N=16) were deployed to the 1990 and 1991 GW but did not meet Center for Disease Control and Prevention criteria for GWI. Results:There were no significant differences in composite scores on the traditional and computerized neuropsychologic battery (automated neuropsychologic assessment metrics) between GW cases and controls using bivariate techniques. Multiple linear regression analyses controlling for demographic and clinical variables revealed composite automated neuropsychologic assessment metrics scores were associated with age (b=−7.8; P=0.084), and education (b=22.9; P=0.0012), but not GW case or control status (b=−63.9; P=0.22). Compared with controls, GW cases had significantly more impairment on the Personality Assessment Inventory and the short form-36. Conclusions:Compared with GW controls, GW cases meeting criteria for GWI had preserved cognition function but had significant psychiatric symptoms and lower quality of life.

The impact of subjective cognitive fatigue and depression on cognitive function in patients with multiple sclerosis

Background: The association between subjective cognitive fatigue and objective cognitive dysfunction in patients with multiple sclerosis (PwMS) has been studied, with conflicting results. Objective: To explore the impact of fatigue on cognitive function, while controlling for the influence of depression, disability, comorbidities, and psychotropic medications. Methods: PwMS completed a computerized cognitive testing battery with age- and education-adjusted cognitive domain scores. Disability (Expanded Disability Status Scale (EDSS)), cognitive fatigue, and depression were concurrently evaluated. Results: In all, 699 PwMS were included. Both cognitive fatigue and depression were significantly and negatively correlated with the same cognitive domains: information processing speed, executive function, attention, motor function, and memory (−0.15 ⩽ r ⩽ −0.14 for cognitive fatigue; −0.24 ⩽ r ⩽ −0.19 for depression). Multivariate analysis revealed significant but small independent correlations only between depression and neuropsychological test results, while cognitive fatigue had no independent correlation with objective cognitive function except for a trend toward impaired motor function in highly fatigued PwMS. Depression and cognitive fatigue accounted for no more than 6% of the variance in objective cognitive domain scores. Conclusion: Cognitive fatigue is not independently related to objective cognitive impairment. Depression may influence cognitive function of PwMS primarily when it is severe. Cognitive impairment in PwMS should not be ascribed to fatigue or mild depression.