Verbal and nonverbal fluency in amyotrophic lateral sclerosis.

Amyotrophic lateral sclerosis (ALS) is a multi-system disorder that commonly affects cognition and behaviour. Verbal fluency impairments are consistently reported in ALS patients, and we aimed to investigate whether this deficit extends beyond the verbal domain. We further aimed to determine whether deficits are underpinned by a primary intrinsic response generation impairment (i.e., a global reduction across tasks), potentially related to apathy, or an inability to maintain responding over time (i.e., a 'drop off' pattern). Twenty-two ALS patients and 21 demographically-matched controls completed verbal and nonverbal fluency tasks (phonemic/semantic word fluency, design fluency, gesture fluency and ideational fluency), requiring the generation of responses over a specified time period. Fluency performance was analysed in terms of the overall number of novel items produced, as well as the number of items produced in the first 'initiation' and the remaining 'maintenance' time periods. ALS patients' overall performance was not globally reduced across tasks. Patients were impaired only on meaningful gesture fluency, which requires the generation of gestures that communicate meaning (e.g., waving). On phonemic fluency, ALS patients showed a 'drop off' pattern of performance, where they had difficulty maintaining responding over time, but this pattern was not evident on the other fluency tasks. Apathy did not appear to be related to fluency performance. The selective meaningful gesture fluency deficit, in the context of preserved meaningless gesture fluency, highlights that the retrieval of action knowledge may be weakened in early ALS.

The Role of Apathy in Spontaneous Verbal and Nonverbal Behaviors: A Transdiagnostic Pilot Study in Neurodegeneration.

BACKGROUND: Apathy, characterized by a quantifiable reduction in motivation or goal-directed behavior, is a multidimensional syndrome that has been observed across many neurodegenerative diseases. OBJECTIVE: To develop a novel task measuring spontaneous action initiation (ie, a nonverbal equivalent to spontaneous speech tasks) and to investigate the association between apathy and executive functions such as the voluntary initiation of speech and actions and energization (ie, ability to initiate and sustain a response). METHOD: We compared the energization and executive functioning performance of 10 individuals with neurodegenerative disease and clinically significant apathy with that of age-matched healthy controls (HC). We also investigated the association between self-reported scores on the Apathy Evaluation Scale (AES) and performance on energization tasks. RESULTS: The individuals with apathy made significantly fewer task-related actions than the HC on the novel spontaneous action task, and their scores on the AES were negatively correlated with spontaneous task-related actions, providing preliminary evidence for the task's construct validity. In addition, the individuals with apathy performed more poorly than the HC on all of the energization tasks, regardless of task type or stimulus modality, suggesting difficulty in sustaining voluntary responding over time. Most of the tasks also correlated negatively with the AES score. However, the individuals with apathy also performed more poorly on some of the executive function tasks, particularly those involving self-monitoring. CONCLUSION: Our work presents a novel experimental task for measuring spontaneous action initiation-a key symptom of apathy-and suggests a possible contribution of apathy to neuropsychological deficits such as poor energization.

Sensitivity and specificity of the ECAS in identifying executive function and social cognition deficits in MND.

Objective: Motor neurone disease [MND] encompasses broad cognitive impairments, which are not fully captured by most screening tools. This study evaluated the specificity and sensitivity of the Edinburgh Cognitive and Behavioral ALS Screen [ECAS] in detecting impairments in executive function and social cognition. Methods: Participants (MND = 64; Healthy Controls = 45) completed the ECAS and standard neuropsychology tests of executive function and social cognition. Sensitivity and specificity of the ECAS were assessed at three levels (ALS-Specific score, executive function domain score, individual subtests: social cognition, inhibition, working memory, alternation). Results: MND patients were impaired on standard social cognition, initiation, visuomotor alternation, and verbal learning tests but not on inhibition or working memory tests, relative to controls. ECAS results revealed that the ALS-Specific score was high in specificity but low-to-moderately sensitive in identifying social cognition, inhibition, and working memory deficits, and that both sensitivity and specificity were high for identifying alternation deficits. The ECAS executive function domain score was high in specificity but poor in sensitivity for all four executive function domain subtests. The individual ECAS subtests were highly specific with good sensitivity, but the social cognition subtest lacked sensitivity. Conclusions: Impairments in social cognition may go undetected when using the ECAS as a screening tool. Thus, social cognition may need to be considered as a standalone component, distinct from the other executive functions. In addition, the test itself may need to be adjusted to encompass other aspects of social cognition that are affected in MND.Key messagesCognitive screening tools are key to detect cognitive changes in MND, with the domains most affected being executive functions, language, and social cognition.The ECAS measure, developed for MND, has good specificity but lacks sensitivity to impairments in social cognition.Clinical implications are that cognitive impairments in social cognition may not be identified in MND patients by the ECAS.Adjustment to the ECAS cognitive screening tool widely-used in MND is suggested.

Implementation of a Hybrid Teleneuropsychology Method to Assess Middle Aged and Older Adults During the COVID-19 Pandemic.

OBJECTIVE: Hybrid teleneuropsychology has emerged as a useful assessment method to manage physical distancing requirements during the COVID-19 pandemic. We describe the development of a hybrid teleneuropsychology clinic and compare results of six neuropsychological tasks across testing modalities, as well as a participant experience survey. METHOD: Healthy middle-aged and older adults completed a face-to-face assessment two years previously. Participants either completed reassessment face-to-face or via the hybrid setup. Results were compared across time points and delivery modality. RESULTS: There were no significant differences in scores at reassessment between face-to-face and a hybrid setup on nonverbal fluid intelligence, verbal memory, visual memory, language, working memory or verbal initiation. Retest reliability was moderate to excellent for verbal and visual memory, attention and naming. Results of an anonymous survey indicated that participants felt comfortable and established good rapport with the examiner. CONCLUSIONS: This hybrid method of teleneuropsychology can be used to obtain high quality and reliable results including on tasks yet to be evaluated for teleneuropsychology, including the Graded Naming Test and the Topographical Recognition Memory Test.

Idea selection for propositional language production.

The ability to select an idea from an array of competing options is critical for successful propositional language production, and deficient idea selection contributes to propositional language impairments in clinical populations. We investigate whether three clinical idea selection tasks are sensitive to selection demands in neurologically unimpaired adults, and whether performance relates to age. 154 neurologically normal adults aged 18-89 years completed a neuropsychological baseline and three  idea selection tasks. Stimuli either activated a dominant response or multiple competing response options. All three idea selection tasks were sensitive to selection demands in terms of reaction times but not errors. Older age was associated with greater effects of selection demands on Sentence Completion task performance only. Exploratory analyses revealed a potential role of executive functioning. Overall, we demonstrate that clinical idea selection tasks are sensitive to idea selection demands in a non-clinical sample, and show some age-related differences in performance.

Fluency test generation and errors in focal frontal and posterior lesions.

The number produced on fluency tasks is widely used to measure voluntary response generation. To further evaluate the relationship between generation, errors, and the area of anatomical damage we administered eight fluency tasks (word, design, gesture, ideational) to a large group of focal frontal (n = 69) and posterior (n = 43) patients and controls (n = 150). Lesions were analysed by a finer-grained frontal localisation method, and traditional subdivisions (anterior/posterior, left/right frontal). Thus, we compared patients with Lateral lesions to patients with Medial lesions. Our results show that all fluency tasks are sensitive to frontal lobe damage for the number of correct responses and, for the first time, we provide evidence that seven fluency tasks show frontal sensitivity in terms of errors (perseverations, rule-breaks). Lateral (not Medial) patients produced the highest error rates, indicative of task-setting or monitoring difficulties. There was a right frontal effect for perseverative errors when retrieving known or stored items and rule-break errors when creating novel responses. Left lateral effects were specific to phonemic word fluency rule-breaks and perseverations for meaningless gesture fluency. In addition, our generation output and error findings support a frontal role in novelty processes. Finally, we confirm our previous generation findings suggesting critical roles of the superior medial region in energization and the left inferior frontal region in selection (Robinson et al., 2012). Overall, these results support the notion that frontal functions comprise a set of highly specialised cognitive processes, supported by distinct frontal regions.

A Goal Intervention Improves Language Fluency: Evidence from Parkinson's Disease and Healthy Aging.

Background: Parkinson's disease [PD] is associated with reduced motor and cognitive initiation, and decreased goal-directed behavior including language generation. The current study investigated a novel goal intervention for language generation impairments in PD patients. Methods: Twenty-one PD patients and 22 healthy controls, matched for gender, age, and education, completed a cognitive baseline and language generation tasks (complex scene descriptions and phonemic/semantic word fluency) with standard and adapted instructions, which implements a target 'goal'. In addition, participants completed self-report questionnaires for apathy and mood. Results: PD patients performed more poorly on two of three language generation tasks. The goal intervention was effective in increasing both the PD patient and healthy control groups' language generation. However, there was no differential benefit of increased goal specificity and difficulty for PD patients. As a group, PD patients reported higher levels of apathy and depression than healthy controls. Specifically, PD patients with executive apathy were more likely to have language generation impairments than PD patients without executive apathy and controls. Apathy subscales and goal benefit were unrelated. Conclusions: The goal intervention was effective for PD patients and older adults, suggesting that enhanced goal specificity and difficulty may benefit individuals with PD or those aging naturally.

A Brief Executive Language Screen for Frontal Aphasia.

Aphasia assessment tools have primarily focused on classical aphasia type and severity, with minimal incorporation of recent findings that suggest a significant role of executive control operations in language generation. Assessment of the interface between language and executive functions is needed to improve detection of spontaneous speech difficulties. In this study we develop a new Brief Executive Language Screen (BELS), a brief tool specifically designed to assess core language and executive functions shown to be involved in spontaneous generation of language. Similar to other measures of aphasia, the BELS assesses articulation and core language skills (repetition, naming and comprehension). Unique additions to the BELS include assessments of spontaneous connected speech, word fluency (phonemic/semantic) and sentence completion (verbal initiation, inhibition and selection). One-hundred and eight healthy controls and 136 stroke patients were recruited. Confirmatory factor analysis was used to determine construct validity and logistic regression was used to evaluate the discriminative validity, informing the final version of the BELS. The results showed that the BELS is sensitive for articulation and nominal language deficits, and it measures executive aspects of spontaneous language generation, which is a hallmark of frontal dynamic aphasia. The results have encouraging theoretical and practical implications.

A prospective cohort study of prodromal Alzheimer's disease: Prospective Imaging Study of Ageing: Genes, Brain and Behaviour (PISA).

This prospective cohort study, "Prospective Imaging Study of Ageing: Genes, Brain and Behaviour" (PISA) seeks to characterise the phenotype and natural history of healthy adult Australians at high future risk of Alzheimer's disease (AD). In particular, we are recruiting midlife and older Australians with high and low genetic risk of dementia to discover biological markers of early neuropathology, identify modifiable risk factors, and establish the very earliest phenotypic and neuronal signs of disease onset. PISA utilises genetic prediction to recruit and enrich a prospective cohort and follow them longitudinally. Online surveys and cognitive testing are used to characterise an Australia-wide sample currently totalling over 3800 participants. Participants from a defined at-risk cohort and positive controls (clinical cohort of patients with mild cognitive impairment or early AD) are invited for onsite visits for detailed functional, structural and molecular neuroimaging, lifestyle monitoring, detailed neurocognitive testing, plus blood sample donation. This paper describes recruitment of the PISA cohort, study methodology and baseline demographics.

The spectrum of language impairments in amyotrophic lateral sclerosis.

Language disorders are increasingly recognised in Amyotrophic lateral sclerosis (ALS), supporting the view of ALS as a multi-system disorder, impacting cognitive and motor function. However, the language impairments are heterogeneous and recent focus has been on determining the language profile across the ALS spectrum with little focus on spontaneous speech. The current study systematically investigated a wide range of language abilities in an unselected ALS sample (N = 22), including spontaneous speech. We analysed the ALS patients' performance as a group, compared to age-, education- and IQ-matched healthy controls (N = 21), and as a case series to identify dementia and specific language profiles. The ALS group was impaired on measures of spontaneous speech, word fluency and action naming. By contrast, object naming, semantic memory (object and actions), sentence comprehension and repetition (word and sentences) were comparable to healthy controls. In line with recent suggestions, our ALS patients' action naming (but not action semantic) deficit does not support the notion that action processing may be selectively impaired in ALS. The case series demonstrated that 14% of patients had probable dementia, 31% showed significant cognitive and/or language impairment and 55% were unimpaired, consistent with the spectrum of cognitive and language impairments reported in the literature. In addition, 36% of ALS patients produced significantly fewer words per minute on a spontaneous speech task than the control group, with this difference remaining when the ALS patients with frontotemporal dementia were excluded from the analysis. This pattern was observed across the ALS spectrum and in both limb and bulbar onset patients. The pattern of performance observed in the present study suggests that spontaneous speech is reduced across the ALS spectrum even in those with intact core language abilities.

Differential patterns of internally generated responses in parkinsonian disorders.

Internally generated responses are centrally affected in parkinsonian disorders. This study investigated the cognitive components crucial for response generation as reflected in performance on verbal and non-verbal fluency tasks, which require voluntary internal generation of multiple responses. Participants with parkinsonian disorders (N = 58: 29 Parkinson's disease [PD], 22 corticobasal syndrome [CBS], 8 progressive supranuclear palsy [PSP]) and 89 age-matched controls completed baseline cognitive assessments and eight fluency tasks of four types: word, design, gesture, and ideational. We analysed the total number of correct responses generated and error rates (including repetitions and rule breaks) for PD, CBS and Control groups. The small PSP patient group's performance is reported for comparative purposes only. CBS patients were significantly reduced in the number of correct responses generated across all fluency tasks, without incurring significant errors. The only exception was that CBS patients produced a significantly higher number of repetitions on one nonverbal task (design fluency). By contrast, PD patients' generation was reduced on only three fluency tasks (phonemic word, meaningless gesture, conventional idea). However, they also produced a high error rate on four fluency tasks (rule-break errors: phonemic/semantic word; repetitions: semantic word, meaningless gestures). Overall, the pattern of fluency task performance differs between patient groups. Specifically, the quantity of responses generated is differentially and primarily affected in CBS patients, whereas the quality of responses generated is primarily affected in PD patients. This suggests potentially different patterns of performance for parkinsonian disorders and has implications for the cognitive processes crucial for internally-guided response generation.

Hypermetabolism in ALS is associated with greater functional decline and shorter survival.

OBJECTIVE: To determine the prevalence of hypermetabolism, relative to body composition, in amyotrophic lateral sclerosis (ALS) and its relationship with clinical features of disease and survival. METHODS: Fifty-eight patients with clinically definite or probable ALS as defined by El Escorial criteria, and 58 age and sex-matched control participants underwent assessment of energy expenditure. Our primary outcome was the prevalence of hypermetabolism in cases and controls. Longitudinal changes in clinical parameters between hypermetabolic and normometabolic patients with ALS were determined for up to 12 months following metabolic assessment. Survival was monitored over a 30-month period following metabolic assessment. RESULTS: Hypermetabolism was more prevalent in patients with ALS than controls (41% vs 12%, adjusted OR=5.4; p<0.01). Change in body weight, body mass index and fat mass (%) was similar between normometabolic and hypermetabolic patients with ALS. Mean lower motor neuron score (SD) was greater in hypermetabolic patients when compared with normometabolic patients (4 (0.3) vs 3 (0.7); p=0.04). In the 12 months following metabolic assessment, there was a greater change in Revised ALS Functional Rating Scale score in hypermetabolic patients when compared with normometabolic patients (-0.68 points/month vs -0.39 points/month; p=0.01). Hypermetabolism was inversely associated with survival. Overall, hypermetabolism increased the risk of death during follow-up to 220% (HR 3.2, 95% CI 1.1 to 9.4, p=0.03). CONCLUSIONS AND RELEVANCE: Hypermetabolic patients with ALS have a greater level of lower motor neuron involvement, faster rate of functional decline and shorter survival. The metabolic index could be important for informing prognosis in ALS.

An unusual presentation of probable dementia: rhyming, associations, and verbal disinhibition.

We report a case of probable Alzheimer's disease who presented with the unusual feature of disinhibited rhyming. Core language skills were largely intact but generative language was characterized by semantic-based associations, evident in tangential and associative content, and phonology-based associations, evident in rhyming, in the context of prominent executive dysfunction. We suggest this pattern is underpinned by a failure to terminate or inhibit verbal associations resulting in a 'loosening' of associations at the level of conceptual preparation for spoken language.