Exploring Social Cognition Tests to Differentiate Frontotemporal Dementia from Depression: A Two-Step Pilot Study.

Behavioral-variant frontotemporal dementia (bvFTD) is challenging to recognize, and often misdiagnosed as depression (DEP). Evidence suggests changes in social cognition (SoCog) precede general cognitive decline in bvFTD. Currently, there are no screening measures of social cognition. 17 bvFTD, 16 DEP, and 18 control participants underwent 6 SoCog tests measuring: emotion recognition; theory of mind; empathy; insight. We used χ 2 , Wilcoxon rank sum, Kruskal-Wallis tests to compare groups, with decision tree analysis to identify items that best differentiated bvFTD from DEP. bvFTD performed significantly worse on all SoCog tasks compared with other groups. Decision tree analysis yielded a 5-item test with ROC area under the curve of 0.973 (95% CI: 0.928, 1.0) for differentiating bvFTD versus depression. These results suggest that it may be feasible to develop a screening measure of social cognition.

The Effects of Chronic Right Hemispheric Damage on the Allocation of Spatial Attention: Alterations of Accuracy and Reliability.

Right hemispheric damage (RHD) caused by strokes often induce attentional disorders such as hemispatial neglect. Most patients with neglect over time have a reduction in their ipsilesional spatial attentional bias. Despite this improvement in spatial bias, many patients remain disabled. The cause of this chronic disability is not fully known, but even in the absence of a directional spatial attentional bias, patients with RHD may have an impaired ability to accurately and precisely allocate their spatial attention. This inaccuracy and variable directional allocation of spatial attention may be revealed by repeated performance on a spatial attentional task, such as line bisection (LBT). Participants with strokes of their right versus left (LHD) hemisphere along with healthy controls (HC) performed 24 consecutive trials of 24 cm horizontal line bisections. A vector analysis of the magnitude and direction of deviations from midline, as well as their standard deviations (SD), were calculated. The results demonstrated no significant difference between the LHD, RHD and HC groups in overall spatial bias (mean bisection including magnitude and direction); however, the RHD group had a significantly larger variability of their spatial errors (SD), and made larger errors (from midline) than did the LHD and HC groups. There was a curvilinear relationship between the RHD participants' performance variability and their severity of their inaccuracy. Therefore, when compared to HC and LHD, the RHD subjects' performance on the LBT is more variable and inaccurate.

Acute lorazepam effects on neurocognitive performance.

A double-blind, placebo-controlled, crossover design was employed to determine whether acute lorazepam (2 mg orally) cognitive side effects would emerge in a differential age-dependent fashion in 15 young (mean age=22 years) and 12 older (mean age=64 years) subjects. Acute use of lorazepam is frequently the initial treatment choice for convulsive status epilepticus or repetitive seizure clusters. Cognitive assessment was performed during drug and placebo conditions using a computerized battery of cognitive tests. With the exception of performance on the reasoning composite score, significant drug effects were present on all primary cognitive domain measures. However, the only significant drug-by-age interaction effect was seen for dual-task performance. The relationship between test performance and plasma lorazepam concentrations was generally modest and non-significant, suggesting that individual differences in pharmacokinetics are not a major factor contributing to the emergence of cognitive side effects. Despite robust lorazepam effects on multiple measures of neurocognitive function, differential age effects are largely restricted to dual-task performance. These results indicate that with the exception of dual-task performance, older individuals in the age range of this study do not appear to be at increased risk for the emergence of cognitive side effects following a single 2-mg dose of lorazepam.

The relationship between semantic knowledge and conceptual apraxia in Alzheimer disease.

BACKGROUND: Conceptual apraxia (CA), a feature of Alzheimer disease (AD), can be detected by asking participants to identify the correct tool to act on an object. Assessment can be based on either learned associations (a tool selection test) or the mechanical properties that the tool needs to alter the target object (an alternative tool selection test). OBJECTIVES: We wanted to determine whether knowledge of semantic taxonomic relations (intrinsic properties shared by items) correlated with performance on tests for CA in people with AD or amnestic mild cognitive impairment (aMCI). METHODS: We tested 10 participants with AD, 12 with aMCI, and 18 healthy older adults for CA using an alternative tool selection test, a tool selection test, and a test of taxonomic relations. RESULTS: The aMCI group did not differ from the control group on the CA tests. The patients with AD were impaired on all tests except tool selection; their performance on the alternative tool selection test correlated significantly with their performance on the taxonomic relations test. CONCLUSIONS: The correlation between performances on the alternative tool selection test and the taxonomic relations test in AD suggests a common pathophysiologic substrate, either impairment in accessing conceptual-semantic representations or a degradation of these representations.

D-CARE: The Dementia Care Study: Design of a Pragmatic Trial of the Effectiveness and Cost Effectiveness of Health System-Based Versus Community-Based Dementia Care Versus Usual Dementia Care.

BACKGROUND/OBJECTIVES: Although several approaches have been developed to provide comprehensive care for persons living with dementia (PWD) and their family or friend caregivers, the relative effectiveness and cost effectiveness of community-based dementia care (CBDC) versus health system-based dementia care (CBDC) and the effectiveness of both approaches compared with usual care (UC) are unknown. DESIGN: Pragmatic randomized three-arm superiority trial. The unit of randomization is the PWD/caregiver dyad. SETTING: Four clinical trial sites (CTSs) based in academic and clinical health systems. PARTICIPANTS: A total of 2,150 English- or Spanish-speaking PWD who are not receiving hospice or residing in a nursing home and their caregivers. INTERVENTIONS: Eighteen months of (1) HSDC provided by a nurse practitioner or physician's assistant dementia care specialist who works within the health system, or (2) CBDC provided by a social worker or nurse care consultant who works at a community-based organization, or (3) UC with as needed referral to the Alzheimer's Association Helpline. MEASUREMENTS: Primary outcomes: PWD behavioral symptoms and caregiver distress as measured by the Neuropsychiatric Inventory Questionnaire (NPI-Q) Severity and Modified Caregiver Strain Index scales. SECONDARY OUTCOMES: NPI-Q Distress, caregiver unmet needs and confidence, and caregiver depressive symptoms. Tertiary outcomes: PWD long-term nursing home placement rates, caregiver-reported PWD functional status, cognition, goal attainment, "time spent at home," Dementia Burden Scale-Caregiver, a composite measure of clinical benefit, Quality of Life of persons with dementia, Positive Aspects of Caregiving, and cost effectiveness using intervention costs and Medicare claims. RESULTS: The results will be reported in the spring of 2024. CONCLUSION: D-CARE will address whether emphasis on clinical support and tighter integration with other medical services has greater benefit than emphasis on social support that is tied more closely to community resources. It will also assess the effectiveness of both interventions compared with UC and will evaluate the cost effectiveness of each intervention.

Spatial attentional bias in normal people: object or viewer-centered.

When bisecting radial lines, normal subjects often have a distal bias. To help in explaining this systematic bias, it has been proposed that normal people have an attentional bias to the top of the lines (object centered hypothesis) or toward stimuli falling in the lower portion of the retina (retinotopic hypotheses) or to distal peripersonal space (body centered hypotheses). The primary aim of this study is to test these hypotheses by having normal subjects bisect radial lines, placed in a clockwise distribution in the transverse plane, below eye level. Our results demonstrate that the perception of the midpoint progressively changes as a function of the body centered orientation of the lines, with subjects demonstrating a progressively greater distal bias as they approached the midsagittal plane or radial condition. These findings provide support for the postulate that distal bias on radial lines bisections is body centered.

Art in the eye of the beholder: the perception of art during monocular viewing.

OBJECTIVE: To explore whether monocular viewing affects judgment of art. BACKGROUND: Each superior colliculus receives optic nerve fibers primarily from the contralateral eye, and visual input to each colliculus activates the ipsilateral hemisphere. In previous studies, monocular viewing influenced performance on visual-spatial and verbal memory tasks. METHOD: Eight college-educated subjects, 6 men and 2 women, monocularly viewed 10 paintings with the right eye and another 10 with the left. Subjects had not previously seen the paintings. Each time, 5 paintings were abstract expressionist and 5 were impressionist. The orders of eye viewing and painting viewed were pseudorandomized and counterbalanced. Subjects rated on a 1 to 10 scale 4 qualities of the paintings: representation, aesthetics (beauty), novelty, and closure (completeness). RESULTS: Paintings in the abstract expressionist style had a significant difference in the rating of novelty; the paintings were rated more novel when viewed with the left eye than with the right eye. There was a trend for rating paintings as having more closure when viewing with the right eye than with the left. Impressionist paintings show no differences. CONCLUSIONS: Monocular viewing influences artistic judgments; novelty being rated higher when viewed with the left eye. Asymmetric projections from each eye and hemispheric specialization are posited to explain these differences.

Effects of aging on action-intentional programming.

BACKGROUND: Action-intentional programs control "when" we initiate, inhibit, continue, and stop motor actions. The purpose of this study was to learn if there are changes in the action-intentional system with healthy aging, and if these changes are asymmetrical (right versus left upper limb) or related to impaired interhemispheric communication. METHODS: We administered tests of action-intention to 41 middle-aged and older adults (61.9 ± 12.3 years). RESULTS: Regression analyses revealed that older age predicted a decrement in performance for tests of crossed motor response inhibition as well as slower motor initiation with the left hand. CONCLUSION: Changes in action-intention with aging appear to be related to alterations of interhemispheric communication and/or age-related right hemisphere dysfunction; however, further research is needed to identify the mechanisms for age-related changes in the brain networks that mediate action-intention.

Lewy body dementia and creativity: case report.

BACKGROUND: We studied a visual artist with Lewy body dementia (LBD) to learn how this disease influenced his paintings during the course of the disease. METHODS: Study 1 evaluated two paintings of the same subject matter, one that the patient painted before his illness and the other after the onset of this disease. Study 2 evaluated a collection of his paintings from the time before he was ill (1994) until the time he stopped painting when he was suffering with LBD (2002). To learn how the onset and progression of LBD affected his paintings we had judges score the following qualities: aesthetic-beauty, closure completeness, evocative impact, novelty, technique and representational quality. RESULTS: In Study 1 we found that the representational ratings for the picture he painted when he had LBD was significantly lower than the picture he painted before he developed LBD. In Study 2, we found that all the artistic qualities measures temporally declined except novelty. We also found that the paintings that were judges as having the highest quality representations were significantly more novel than those that had poorer representations. In addition, we conducted a forward stepwise regression analysis using quality measures as predictor of year. This analysis revealed that only representational quality significantly predicted painting year. CONCLUSIONS: Our results suggest that as LBD progresses, except for novelty there is a gradual degradation of the ability to visually express artistic subject matter. It possible that the preserved ability to paint novel picture is related to relative preservation of frontal lobe function, but the degradation of other artistic qualities might be related to deterioration of the parietal lobes which either impairs the brain's iconic representations or the knowledge needed to portray these representations.

Assessment of Mental Status.

Assessing the mental status of patients with a neurobehavioral disorder is a critical element in the diagnosis and treatment of these patients. This assessment should always be performed after the patient's history it taken and a general physical as well as a neurologic examination is completed. The mental status examination commences with observing the patient's appearance and level of consciousness. The examiner should also pay attention to patient's social behavior, emotional state and mood. There are 3 major means of assessing a patient's mental status. One type attempts to determine if the patient is demented and the severity of the dementia as it pertains to their ability to perform activities of daily living as well as instrumental activities. A second type of assessment utilizes what may be termed as "screening tests" or "omnibus tests". These brief tests are performed independent of the patient's history and examination. The two most frequently used screening tests are the Mini-Mental Status Examination (MMSE) and the Montreal Cognitive Assessment (MoCA). The third means of assessing a patient's mental status is by using specific neuropsychological tests that focus on specific domains of cognition, such as frontal executive functions, attention, episodic verbal and visuospatial memory, declarative knowledge such as language (speech, reading and writing) and arithmetical, as well as visuospatial and perceptual abilities. These neurobehavioral, neuropsychiatric and neuropsychological assessments of patients with a cognitive decline and behavioral abnormalities should often be accompanied by laboratory tests, and neuroimaging that can help determine the underlying pathologic process so that effective therapeutic and management approaches can be provided.

Perceptual-motor dysfunction.

PURPOSE OF REVIEW: This article highlights the importance of integrated perceptual information (motor planning, sequencing, and representation) and discusses the integration of these cognitive domains by means of feedforward and feedback loops in the successful acquisition and execution of voluntary behaviors. The article also discusses the dysfunction in the perceptual-motor process that can occur with neurologic injury, resulting in apraxias, agnosia, hemineglect, and Balint syndrome. RECENT FINDINGS: A combination of functional imaging and lesional studies continues to refine our understanding of the role of the posterior parietal region in the integration of perception with motor action. Different disorders provide contrasting views into the nature of perceptual-motor function and its disruption. Novel rehabilitation techniques may provide improved function in the future. SUMMARY: Studies continue to demonstrate the importance of unimodal and heteromodal association cortices, as well as the extrapyramidal system (especially the basal ganglia) in perceptual-motor functions across a wide range of activities and disease states. The nondominant hemisphere dictates where attention and intention are to be directed in space, and the dominant hemisphere provides information on how to accomplish skilled complex actions. While the role of perceptual-motor dysfunction in developmental disorders has been long considered, the role of perceptual-motor dysfunction in neurodegenerative diseases, from Parkinson disease to corticobasal syndrome to posterior cortical atrophy, is becoming more apparent. A clear need exists for more robust rehabilitation strategies in these neurodegenerative diseases.

Understanding Empathy Training with Virtual Patients.

While the use of virtual characters in medical education is becoming more and more commonplace, an understanding of the role they can play in empathetic communication skills training is still lacking. This paper presents a study aimed at building this understanding by determining if students can respond to a virtual patient's statement of concern with an empathetic response. A user study was conducted at the [blinded] College of Medicine in which early stage medical students interacted with virtual patients in one session and real humans trained to portray real patients (i.e., standardized patients) in a separate session about a week apart. During the interactions, the virtual and 'real' patients presented the students with empathetic opportunities which were later rated by outside observers. The results of pairwise comparisons indicate that empathetic responses made to virtual patients were rated as significantly more empathetic than responses made to standardized patients. Even though virtual patients may be perceived as artificial, the educational benefit of employing them for training medical students' empathetic communications skills is that virtual patients offer a low pressure interaction which allows students to reflect on their responses.

Improving clinical cognitive testing: report of the AAN Behavioral Neurology Section Workgroup.

OBJECTIVE: To evaluate the evidence basis of single-domain cognitive tests frequently used by behavioral neurologists in an effort to improve the quality of clinical cognitive assessment. METHODS: Behavioral Neurology Section members of the American Academy of Neurology were surveyed about how they conduct clinical cognitive testing, with a particular focus on the Neurobehavioral Status Exam (NBSE). In contrast to general screening cognitive tests, an NBSE consists of tests of individual cognitive domains (e.g., memory or language) that provide a more comprehensive diagnostic assessment. Workgroups for each of 5 cognitive domains (attention, executive function, memory, language, and spatial cognition) conducted evidence-based reviews of frequently used tests. Reviews focused on suitability for office-based clinical practice, including test administration time, accessibility of normative data, disease populations studied, and availability in the public domain. RESULTS: Demographic and clinical practice data were obtained from 200 respondents who reported using a wide range of cognitive tests. Based on survey data and ancillary information, between 5 and 15 tests in each cognitive domain were reviewed. Within each domain, several tests are highlighted as being well-suited for an NBSE. CONCLUSIONS: We identified frequently used single-domain cognitive tests that are suitable for an NBSE to help make informed choices about clinical cognitive assessment. Some frequently used tests have limited normative data or have not been well-studied in common neurologic disorders. Utilizing standardized cognitive tests, particularly those with normative data based on the individual's age and educational level, can enhance the rigor and utility of clinical cognitive assessment.

Status of neurology medical school education: results of 2005 and 2012 clerkship director survey.

OBJECTIVE: To survey all US medical school clerkship directors (CDs) in neurology and to compare results from a similar survey in 2005. METHODS: A survey was developed by a work group of the American Academy of Neurology Undergraduate Education Subcommittee, and sent to all neurology CDs listed in the American Academy of Neurology database. Comparisons were made to a similar 2005 survey. RESULTS: Survey response rate was 73%. Neurology was required in 93% of responding schools. Duration of clerkships was 4 weeks in 74% and 3 weeks in 11%. Clerkships were taken in the third year in 56%, third or fourth year in 19%, and fourth year in 12%. Clerkship duration in 2012 was slightly shorter than in 2005 (fewer clerkships of ≥4 weeks, p = 0.125), but more clerkships have moved into the third year (fewer neurology clerkships during the fourth year, p = 0.051). Simulation training in lumbar punctures was available at 44% of schools, but only 2% of students attempted lumbar punctures on patients. CDs averaged 20% protected time, but reported that they needed at least 32%. Secretarial full-time equivalent was 0.50 or less in 71% of clerkships. Eighty-five percent of CDs were "very satisfied" or "somewhat satisfied," but more than half experienced "burnout" and 35% had considered relinquishing their role. CONCLUSION: Trends in neurology undergraduate education since 2005 include shorter clerkships, migration into the third year, and increasing use of technology. CDs are generally satisfied, but report stressors, including inadequate protected time and departmental support.

Recall of word lists is enhanced with increased spreading activation.

Some evidence exists supporting a relationship between spreading activation in semantic/lexical memory networks and episodic memory. However, the results have been mixed and there have been no investigations examining whether a relationship exists between variability in spreading activation and episodic memory. Hence, we sought to investigate these potential relationships. Thirteen individuals were administered the Hopkins Verbal Learning Test-Revised (HVLT-R) and the Controlled Oral Word Association Test (COWAT). The average word frequency of all the "F" words generated on the COWAT was used as a measure of spreading activation. Variability in spreading activation was assessed by calculating the variability of the word frequencies from the COWAT across time. The results confirmed our hypotheses, with significant negative correlations found between free recall on the HVLT-R and both the average word frequency and measures of variability in spreading activation.

Lorazepam effects on Word Memory Test performance: a randomized, double-blind, placebo-controlled, crossover trial.

The Word Memory Test (WMT) is a common measure of symptom validity. To investigate the effects of acute benzodiazepines on WMT scores, oral lorazepam 2 mg (LOR) and placebo were administered 1 week apart in a randomized, double-blind, placebo-controlled, crossover study. A total of 28 participants completed the study and were administered the WMT during each drug condition. Within-participant comparisons of LOR vs placebo revealed significant LOR effects for Immediate Recognition (p = .007) and Consistency (p = .019), but not Delayed Recognition (p = .085). Significant LOR effects were present for Reaction Time Measures (Immediate Recognition RT, p = .013; Delayed Recognition RT, p = .001; Multiple Choice RT, p = .011) and Delayed Memory scores (Multiple Choice, p = .007; Paired Associates, p = .029; Free Recall, p = .001). A pattern similar to crossover results was detected for LOR vs placebo between-group differences for initial test assessment scores. When examined using publisher recommended cut scores for the principal WMT measures, there were six participants failing the WMT during initial LOR testing; all six subsequently performed in the normal range upon retesting with placebo. One participant failed WMT during placebo and obtained passing scores during LOR. These data indicate that multiple WMT measures may be affected by acute LOR dosing, and provide additional evidence that potential latent variables and their effects on both SVT performance and cognitive function should be part of the clinical decision-making process.

Auditory responsive naming versus visual confrontation naming in dementia.

Dysnomia is typically assessed during neuropsychological evaluation through visual confrontation naming. Responsive naming to description, however, has been shown to have a more distributed representation in both fMRI and cortical stimulation studies. While naming deficits are common in dementia, the relative sensitivity of visual confrontation versus auditory responsive naming has not been directly investigated. The current study compared visual confrontation naming and auditory responsive naming in a dementia sample of mixed etiologies to examine patterns of performance across these naming tasks. A total of 50 patients with dementia of various etiologies were administered visual confrontation naming and auditory responsive naming tasks using stimuli that were matched in overall word frequency. Patients performed significantly worse on auditory responsive naming than visual confrontation naming. Additionally, patients with mixed Alzheimer's disease/vascular dementia performed more poorly on auditory responsive naming than did patients with probable Alzheimer's disease, although no group differences were seen on the visual confrontation naming task. Auditory responsive naming correlated with a larger number of neuropsychological tests of executive function than did visual confrontation naming. Auditory responsive naming appears to be more sensitive to effects of increased of lesion burden compared to visual confrontation naming. We believe that this reflects more widespread topographical distribution of auditory naming sites within the temporal lobe, but may also reflect the contributions of working memory and cognitive flexibility to performance.

Normal pressure hydrocephalus.

Normal Pressure Hydrocephalus first became recognized as a treatable, reversible disorder in the 1960s. The classic triad of magnetic apraxia, urinary incontinence, and dementia remain relevant into the 21(st) century as being the basis for symptomatic diagnosis and predicting potential benefit from ventriculoperitoneal shunting, though they have been greatly augmented by the addition of modern neuroimaging, particularly MRI. Modern criteria recognize a wider range of diagnostic criteria, and new positive and negative prognostic indicators for treatment benefit have been discovered, though the mainstay remains initial drainage of a large volume of cerebrospinal fluid and monitoring for clinical improvement. Even with our advances in understanding both primary and secondary normal pressure hydrocephalus, diagnosis, management, and counseling remain challenging in this disorder.

Reversible dementias.

The causes of potentially reversible dementia syndromes are legion, as many perturbations of body chemistry can lead to dysfunction of higher cortical function, including the chemical interventions we call medication. It is vital for the cautious clinician to take a painstaking history to develop a differential diagnosis of potential causally related reversible phenomena. This, coupled with an extensive examination and a widecast net of serological, and when appropriate, cerebrospinal, electrophysiologic, and neuroimaging studies can increase the potential for discovering these mimics of the primary neurodegenerative dementias. While some cases of reversible dementia will be obvious from history and physical and only require a few confirmatory tests or even just a trial of treatment (or often, discontinuation of a suspect treatment), it is worthwhile to perform more extensive work-up in cases of dementia, as the costs to allowing our patients to remain in an incapacitated, possibly progressive, state of disability far outweigh the costs of ruling out reversible causes. This chapter provides a lengthy, though by no means exhaustive, review of etiologies and work-up for the currently recognized reversible dementias.