Measures Of Verbal Fluency Research Articles

Feasibility and reliability of telephone‐based cognitive assessment in middle‐aged and older adults in the Wisconsin Alzheimer’s Disease Research Center

AbstractBackgroundUse of telephone‐based cognitive assessments became more widespread during the COVID‐19 pandemic. The National Alzheimer’s Coordinating Center (NACC) developed the telephone‐based cognitive battery (T‐Cog) to ensure continued data collection and participant retention. The objective of this study was to (1) assess the feasibility and reliability of T‐Cog data collected during the pandemic, (2) evaluate these data in the context of prior in‐person data and (3) inform future use of remote data collection.MethodThe Wisconsin ADRC Clinical Core staff administered T‐Cog batteries to participants with normal cognition, mild cognitive impairment (MCI), or dementia (n = 380, mean age = 68.7±8.9, 66.1% female, 78.4% white, mean education = 16.2±2.48) (Table 1). Examiners rated the validity of the testing session and noted reasons for an invalid session. Reliability was assessed by comparing individual neuropsychological test performances from the T‐Cog to the most recent in‐person evaluation using intraclass correlation coefficients (ICC). Chi‐square was used to test if research diagnoses (normal cognition, MCI, dementia) varied by modality (T‐Cog, in‐person).ResultsMost T‐Cog sessions were rated as valid by examiners (87.8%). The most common reasons for questionable or not valid session included hearing impairments, distractions, and interruptions (Figure 1). Measures of verbal fluency (Animal Naming (ICC = 0.69), F+L Fluency (ICC = 0.73)), list‐learning and memory (RAVLT Trials 1–5 (ICC = 0.75), RAVLT Long Delay Recall (ICC = 0.70), RAVLT Recognition (ICC = 0.71)), and story memory (Craft Story‐Immediate (ICC = 0.65), Craft Story‐Delayed (ICC = 0.73)) showed moderate to excellent reliability and were significant (p<0.01), suggesting good agreement between T‐Cog and in‐person assessments (Table 2). Measures of attention (Digit Span Forward (ICC = 0.66), Digit Span Backward (ICC = 0.15)) varied from moderately reliable to not reliable, respectively. Lastly, research diagnoses did not differ by testing modality.ConclusionThese results suggest T‐Cog assessments are feasible for participants who cannot complete in‐person visits, given adequate hearing and limited distractions and interruptions to ensure test validity. Preliminary comparisons of T‐Cog vs in‐person performances suggest good reliability for verbal fluency, story memory, and list‐learning measures. Although remote assessments can expand access and diversify the population involved in AD research, identifying assessments that are both feasible and reliable across varied administrations will be essential to track longitudinal change in cognitive status.

CTNI-06. IMPROVING INSOMNIA IN PATIENTS WITH PRIMARY BRAIN TUMORS USING COGNITIVE BEHAVIORAL THERAPY: RESULTS FROM AN NRG NCORP PILOT TRIAL

Abstract BACKGROUND Sleep disturbance is among the most common symptoms endorsed by patients with primary brain tumor (PwPBT), with many reporting clinically-elevated insomnia and poor management of sleep-related symptoms by their medical team. Though Cognitive Behavioral Therapy for Insomnia (CBT-I) remains the front-line treatment for sleep disturbance, CBT-I has yet to be evaluated in PwPBT. METHODS PwPBT were recruited locally by direct referral and fliers, and nationally by social media support group postings. Forty PwPBT and insomnia enrolled in a six-week group-based telehealth CBT-I phase IIa single-arm proof-of-concept trial: 50.0% female, 68.2% non-Hispanic white, 55.0% high-grade, 42.5% oligodendroglioma, Mage = 52.4 (SD = 12.0, range 31-77). Participants completed data collection at baseline and post-intervention. Self-report measures assessed insomnia (ISI), fatigue (BFI), mood (PHQ-9, GAD-7) and quality-of-life (QLQ-30). Cognitive assessment included measures of attention (WAIS-IV Digits, TMT), verbal fluency (COWAT) and memory (HVLT). Intervention effects for self-report outcomes were analyzed using paired t-tests; effects for cognitive outcomes were analyzed using repeated-measures ANCOVA controlling for age. RESULTS Among those with complete data (n=34), significant improvements were identified for insomnia (t(33) = 8.6, p < .001, Cohen’s d = 1.5) and fatigue (t(30) = 4.7, p < .001, Cohen’s d = 0.8) symptoms. Depression (t(33) = 5.2, p < .001, Cohen’s d = 0.9) and anxiety symptoms (t(33) = 4.2, p < .001, Cohen’s d = 0.7) also improved. Quality-of-life improved with respect to role (t(33) = 2.8, p = .01, Cohen’s d = 0.5), emotional (t(33) = 2.8, p = .01, Cohen’s d = 0.5), cognitive (t(33) = 3.9, p < .001, Cohen’s d = 0.7), and social functioning (t(33) = 3.5, p = .001, Cohen’s d = 0.6)—but not physical functioning (t(33) = 0.5, p = .60, Cohen’s d = 0.1). No clinically or statistically significant cognitive changes were found. CONCLUSION This trial is the first to preliminarily assess efficacy of CBT-I, a non-pharmacological treatment for insomnia, in PwPBT. Results suggest promising benefit of CBT-I in insomnia severity, fatigue, mood, and most quality-of-life indices for individuals challenged by PBT and insomnia. These findings support further study in a scientifically rigorous phase IIb randomized feasibility trial.

Does Assessment Format Matter? A Comparison of In-Person Versus Teletesting Scores for Youth with ADHD

Objective: This study examined test score equivalency between traditional in-person assessment and teletesting among youth diagnosed with Attention-Deficit/Hyperactivity Disorder (ADHD). Method: In all, 896 youth with ADHD, ages 5–21 years, were administered cognitive, academic achievement, and verbal fluency measures via either teletesting (n = 448) or traditional in-person assessment (n = 448). The teletesting and in-person groups were matched on age, sex, and insurance type (as a proxy for income). Results: Results indicated no significant differences in test scores obtained via in-person and teletesting evaluations across all examined measures. Conclusion: Clinically referred youth with ADHD perform similarly on measures of cognitive functioning, academic achievement, and verbal fluency, regardless of whether these measures are administered in-person or via teletesting. While additional evidence for equivalent psychometric properties of neuropsychological instruments administered remotely is needed, this study offers support for the validity of remote administration among youth with ADHD.

Association between descending pain modulatory system and cognitive impairment in fibromyalgia: A cross-sectional exploratory study.

BackgroundThe successful regulation of sensory input to the central nervous system depends on the descending pain modulatory system (DPMS). For the effective regulation of sensory input to the central nervous system and behavioral responses to pain, the DPMS is required. Its connection to fibromyalgia (FM)-related cognitive dysfunction has not yet been investigated. Therefore, this study tested whether measures of verbal fluency, sustained attention, and short-term and working memory could distinguish FM patients from healthy controls (HC). Additionally, it investigated, using a standardized paradigm, the link between cognitive ability and the function of the DPMS in responders and non-responders to the conditioned pain modulation test (CPM-test).Materials and methodsWe enrolled 21 HC women and 69 FM patients, all of whom ranged in age from 30 to 65. We employed scores from the Trail Making Test (TMTB-A) (sustained and divided attention), the Controlled Oral Word Association Test (COWAT) (orthographic and semantic fluency), and the Digits subtest of the Wechsler Adult Intelligence Scale (WAIS-III) as dependent variables.ResultsA generalized linear model (GLM) adjusted by educational level revealed significantly lower scores in FM than HC on the Span digits forward, COWAT-orthographic, and TMTB-A. For FM patients, multilevel MANCOVA revealed that the cognitive performance of non-responders compared to responders to CPM-test showed lower adjusted scores in Span digits forward (Partial-η2 = 0.358, P = 0.001), Span digits backward (Partial-η2 = 0.358, P = 0.001), COWAT-orthographic (Partial-η2 = 0.551, P = 0.001), COWAR-semantic (Partial-η2 = 0.355, P = 0.001), and TMTB-A (Partial-η2 = 0.360, P = 0.001). The association between the cognitive tests and the DPMS is moderated by the serum level of brain-derived neurotrophic factor (BDNF). Additionally, these cognitive assessments had a positive correlation with antidepressant use and pain threshold. The cognitive assessments, on the other hand, were conversely associated with a life of quality.ConclusionBased on these findings, it can be shown that HC performed substantially better on cognitive exams than FM did. They demonstrated a link between clinical complaints about attention and memory and decreased DPMS effectiveness. Additionally, they demonstrated that the BDNF is a moderating element in a potential relationship between the severity of cognitive impairment and DPMS dysfunction.

Air pollution exposure in mid-life and cognition over 25 years later: a prospective longitudinal cohort study

Background and aim: Existing evidence of the association between air pollution and cognition uses cross-sectional or longitudinal studies with short observation periods. The objective of this research was to investigate this association over a 25-year period. Methods: Data were obtained from the MRC National Survey of Health and Development comprising 2125 participants at age 68-70. Annual average sulphur dioxide (SO2), nitrogen dioxide (NO2), and black smoke (BS) air pollution measurement units were obtained from land use regression models and were assigned to place of residence for 1989 and 2010-2011 (only for NO2) when participants were 43- and 64/65-year-old. Cognition was assessed at ages 68-70 using the Addenbrooke's cognitive examination III (ACE-III), which includes measures of attention, memory, verbal fluency, visuospatial skills, and language. Prospective associations between air pollution and cognition over this ~25-year period was investigated using linear regression models adjusted for socioeconomic and neighbourhood-related indicators. Results: The median (IQR) μg/m3 levels of pollutants in which participants were exposed at age 43 were 28.2 (8.1) for SO2, 29.8 (10.2) for NO2, 11.4 (5.9) for BS and 22.5 (9.1) for NO2 at age 64/65. No associations were observed between pollutants at ages 43 and 64/65 and total score of ACE-III. We found evidence of increases in NO2 and BS at age 43 to be associated with a reduction in total scores for attention (NO2: mean difference (MD) across the interquartile range: -0.27; 95% CI: -0.45 to -0.08; BS: MD: -0.23; 95% CI: -0.36 to -0.10) and memory (BS; MD: -0.23; 95% CI: -0.36 to -0.10). Conclusions: The findings suggest that outdoor air pollution in mid-adulthood could potentially affect cognition in later life. Whilst causation cannot be proved, this work suggests decreases in cognitive ability in later life may be avoided with improved air quality. Keywords: Air pollution, birth cohorts, cognition

Associating persistent self-reported cognitive decline with neurocognitive decline in older breast cancer survivors using machine learning: The Thinking and Living with Cancer study

IntroductionMany cancer survivors report cognitive problems following diagnosis and treatment. However, the clinical significance of patient-reported cognitive symptoms early in survivorship can be unclear. We used a machine learning approach to determine the association of persistent self-reported cognitive symptoms two years after diagnosis and neurocognitive test performance in a prospective cohort of older breast cancer survivors. Materials and methodsWe enrolled breast cancer survivors with non-metastatic disease (n = 435) and age- and education-matched non-cancer controls (n = 441) between August 2010 and December 2017 and followed until January 2020; we excluded women with neurological disease and all women passed a cognitive screen at enrollment. Women completed the FACT-Cog Perceived Cognitive Impairment (PCI) scale and neurocognitive tests of attention, processing speed, executive function, learning, memory and visuospatial ability, and timed activities of daily living assessments at enrollment (pre-systemic treatment) and annually to 24 months, for a total of 59 individual neurocognitive measures. We defined persistent self-reported cognitive decline as clinically meaningful decline (3.7+ points) on the PCI scale from enrollment to twelve months with persistence to 24 months. Analysis used four machine learning models based on data for change scores (baseline to twelve months) on the 59 neurocognitive measures and measures of depression, anxiety, and fatigue to determine a set of variables that distinguished the 24-month persistent cognitive decline group from non-cancer controls or from survivors without decline. ResultsThe sample of survivors and controls ranged in age from were ages 60–89. Thirty-three percent of survivors had self-reported cognitive decline at twelve months and two-thirds continued to have persistent decline to 24 months (n = 60). Least Absolute Shrinkage and Selection Operator (LASSO) models distinguished survivors with persistent self-reported declines from controls (AUC = 0.736) and survivors without decline (n = 147; AUC = 0.744). The variables that separated groups were predominantly neurocognitive test performance change scores, including declines in list learning, verbal fluency, and attention measures. DiscussionMachine learning may be useful to further our understanding of cancer-related cognitive decline. Our results suggest that persistent self-reported cognitive problems among older women with breast cancer are associated with a constellation of mild neurocognitive changes warranting clinical attention.

The relationship between cognitive reserve and cognition in healthy adults: a systematic review

The concept of Cognitive Reserve (CR) refers to the individual differences allowing some people to cope better with brain pathology. The aim of the present review was to explore the relationship between CR and cognition in adulthood. This association has been addressed in several neuro(psycho)logical disorders and in healthy elderly people. However, few studies explored this issue in adulthood (age range 18–65), when individuals might take advantage the most from psychoeducational approaches aimed at increasing CR. For our systematic review, we selected studies assessing CR and adopting neuropsychological and experimental tasks for evaluation of cognitive functioning in healthy individuals. In the selected articles, we examined the relationship of singular proxies, composite indexes or standardized scales of CR with measures of general cognition, attention, inhibitory control, verbal fluency, constructional abilities, and verbal and spatial memory. The results suggested a positive relationship between singular CR proxies, composite indexes or standardized scales, and almost all the explored cognitive domains. No clear conclusion could be made on constructional abilities due to the scarcity of available studies. CR seems associated with better cognitive performance in adulthood, but definite methodological improvements and the use of standardized scales for CR are necessary to reduce inconsistencies among studies.

Novel computerized neurocognitive test battery is sensitive to cancer-related cognitive deficits in survivors.

There is increasing interest in developing new methods to improve sensitivity in detecting subtle cognitive deficits associated with cancer and its treatments. The current study aimed to evaluate the ability of a novel computerized battery of cognitive neuroscience-based tests to discriminate between cognitive performance in breast cancer survivors and controls. Breast cancer survivors (N = 174) and age-matched non-cancer controls (N = 183) completed the Enformia Cogsuite Battery of cognitive assessments, comprised of 7 computerized tests of multiple cognitive domains. Primary outcome measures included accuracy, reaction times (RT), and coefficients of variation (CV) for each task, as well as global scores of accuracy, RT, and CV aggregated across tests. Linear regressions adjusting for age, education, and remote vs. in-office administration showed that compared to non-cancer controls, survivors had significantly lower performance on measures of attention, executive function, working memory, verbal ability, visuospatial ability, and motor function. Survivors had significantly greater CV on measures of attention, working memory, and processing speed, and significantly slower RT on measures of verbal fluency. The Cogsuite battery demonstrates sensitivity to cancer-related cognitive dysfunction across multiple domains, and is capable of identifying specific cognitive processes that may be affected in survivors. The sensitivity of these tasks to subtle cognitive deficits has advantages for initial diagnosis of cancer-related cognitive dysfunction, as well as detecting changes in survivors' cognitive function over time. The remote delivery of the battery may help overcome barriers associated with in-office administration and increase access to neurocognitive evaluation.

Neuropsychology and MRI correlates of neurodegeneration in SPG11 hereditary spastic paraplegia

BackgroundSPG11-linked hereditary spastic paraplegia is characterized by multisystem neurodegeneration leading to a complex clinical and yet incurable phenotype of progressive spasticity and weakness. Severe cognitive symptoms are present in the majority of SPG11 patients, but a systematic and multidimensional analysis of the neuropsychological phenotype in a larger cohort is lacking. While thinning of the corpus callosum is a well-known structural hallmark observed in SPG11 patients, the neuroanatomical pattern of cortical degeneration is less understood. We here aimed to integrate neuropsychological and brain morphometric measures in SPG11.MethodsWe examined the neuropsychological profile in 16 SPG11 patients using a defined neuropsychological testing battery. Long-term follow up testing was performed in 7 patients. Cortical and subcortical degeneration was analyzed using an approved, artificial intelligence based magnetic resonance imaging brain morphometry, comparing patients to established reference values and to matched controls.ResultsIn SPG11 patients, verbal fluency and memory as well as frontal-executive functions were severely impaired. Later disease stages were associated with a global pattern of impairments. Interestingly, reaction times correlated significantly with disease progression. Brain morphometry showed a significant reduction of cortical and subcortical parenchymal volume following a rostro-caudal gradient in SPG11. Whereas performance in memory tasks correlated with white matter damage, verbal fluency measures showed strong associations with frontal and parietal cortical volumes.ConclusionsThe present data will help define neuropsychological and imaging read out parameters in early as well as in advanced clinical stages for future interventional trials in SPG11.

Validation of At-Home Application of a Digital Cognitive Screener for Older Adults.

Standardized neuropsychological assessments of older adults are important for both clinical diagnosis and biobehavioral research. Over decades, in-person testing has been the basis for population normative values that rank cognitive performance by demographic status. Most recently, digital tools have enabled remote data collection for cognitive measures, which offers the significant promise to extend the basis for normative values to be more inclusive of a larger cross section of the older population. We developed a Remote Characterization Module (RCM), using a speech-to-text interface, as a novel digital tool to administer an at-home, 25-min cognitive screener that mimics eight standardized neuropsychological measures. Forty cognitively healthy participants were recruited from a longitudinal aging research cohort, and they performed the same measures of memory, attention, verbal fluency and set-shifting in both in-clinic paper-and-pencil (PAP) and at-home RCM versions. The results showed small differences, if any, for how participants performed on in-person and remote versions in five of eight tasks. Critically, robust correlations between their PAP and RCM scores across participants support the finding that remote, digital testing can provide a reliable assessment tool for rapid and remote screening of healthy older adults’ cognitive performance in several key domains. The implications for digital cognitive screeners are discussed.

How well does the discrepancy between semantic and letter verbal fluency performance distinguish Alzheimer’s dementia from typical aging?

ABSTRACT In Alzheimer’s dementia (AD), greater declines in semantic fluency (SF) relative to letter fluency (LF) have been assumed to reflect semantic disintegration. However, the same pattern is observed in typical aging and neurodegenerative disorders besides AD. We examined this assumption by comparing different aspects of SF and LF performance in older adults with and without dementia, and identifying which verbal fluency measures most clearly distinguish AD from typical aging. Verbal fluency data were compared from 109 individuals with AD and 66 typically aging adults. Correct items, clusters, and errors were analyzed using both raw counts and proportions. Regression analyses examined Task-by-Group interactions and the impact of demographic variables on verbal fluency measures. ROC analyses examined the sensitivity and specificity of the different outcome measures. In regressions, interactions were found for raw but not proportional data, indicating that different group patterns were driven largely by the number of correct items produced. Similarly, in ROC analyses, raw SF totals showed stronger discriminability between groups than either raw discrepancy scores (SF–LF) or discrepancy ratios (SF/LF). Age and cognitive status (MMSE) were the strongest individual predictors of performance. Findings suggest that AD entails quantitative declines in verbal fluency, but qualitatively similar patterns of performance relative to typically aging adults. Thus, SF declines in AD seem to be at least partially attributable to an exaggeration of the underlying mechanisms common to typical aging, and do not necessarily implicate semantic disintegration.

Cognitive profiles and clinical factors in type III spinal muscular atrophy: a preliminary study

Cognitive abilities are often affected in progressive neurodegenerative disorders, but there is a lack of understanding about whether spinal muscular atrophy (SMA) patients experience cognitive deficits and, if so, whether they are associated with clinical factors. A sample of 22 type III SMA patients and 22 healthy controls completed a comprehensive neuropsychological battery, including tests in memory, executive function, language, visuospatial, and global cognitive functioning. Clinical severity was assessed using the Hammersmith Functional Motor Scale, the Revised Upper Limb Module and the Six Minute Walk Test. SMA patients showed poorer performance in visuospatial abilities, executive functions and language as compared to healthy controls. In the SMA sample, patients with greater motor difficulties had lower performance in attention, but higher performance in measures of language, verbal fluency, and memory. In men, but not women, cognitive test performance was associated with motor functioning. Our findings showing cognitive changes in SMA type III may reflect the presence of intrinsic brain pathology and cognitive adaptation mechanisms following physical dysfunction, which may be mediated by other factors, such as sex.

Trajectories of Cognitive Decline in Brain Donors With Autopsy-Confirmed Alzheimer Disease and Cerebrovascular Disease.

Cerebrovascular disease (CBVD) is frequently comorbid with autopsy-confirmed Alzheimer disease (AD), but its contribution to the clinical presentation of AD remains unclear. We leveraged the National Alzheimer's Coordinating Center (NACC) uniform and neuropathology datasets to compare the cognitive and functional trajectories of AD+/CBVD+ and AD+/CBVD- brain donors. The sample included NACC brain donors with autopsy-confirmed AD (Braak stage ≥3, Consortium to Establish a Registry for Alzheimer's Disease score ≥2) and complete Uniform Data Set (UDS) evaluations between 2005 and 2019, with the most recent UDS evaluation within 2 years of autopsy. CBVD was defined as moderate to severe arteriosclerosis or atherosclerosis. We used propensity score weighting to isolate the effects of comorbid AD and CBVD. This method improved the balance of covariates between the AD+/CBVD+ and AD+/CBVD- groups. Longitudinal mixed-effects models were assessed with robust bayesian estimation. UDS neuropsychological test and the Clinical Dementia Rating Scale Sum of Boxes (CDR-SB) scores were primary outcomes. Of 2,423 brain donors, 1,476 were classified as AD+/CBVD+. Compared with AD+/CVBD- donors, the AD+/CBVD+ group had accelerated decline (i.e., group × time effects) on measures of processing speed (β = -0.93, 95% CI -1.35, -0.51, Bayes factor [BF] 130.75), working memory (β = 0.05, 95% CI 0.02, 0.07, BF 3.59), verbal fluency (β = 0.10, 95% CI 0.04, 0.15, BF 1.28), naming (β = 0.09, 95% CI 0.03, 0.16, BF = 0.69), and CDR-SB (β = -0.08, 95% CI -0.12, -0.05, BF 18.11). Effects ranged from weak (BFs <3.0) to strong (BFs <150). We also found worse performance in the AD+/CBVD+ group across time on naming (β = -1.04, 95% CI -1.83, -0.25, BF 2.52) and verbal fluency (β = -0.73, 95% CI -1.30, -0.15, BF 1.34) and more impaired CDR-SB scores (β = 0.45, 95% CI 0.01, 0.89, BF 0.33). In brain donors with autopsy-confirmed AD, comorbid CBVD was associated with an accelerated functional and cognitive decline, particularly on neuropsychological tests of attention, psychomotor speed, and working memory. CBVD magnified effects of AD neuropathology on semantic-related neuropsychological tasks. Findings support a prominent additive and more subtle synergistic effect for comorbid CBVD neuropathology in AD.

Breaking the flow of thought: Increase of empty pauses in the connected speech of people with mild and moderate Alzheimer's disease

IntroductionThe profile of spontaneous speech in Alzheimer's disease (AD) includes increased pausing as a window into cognitive decline. We here aimed to further characterize the pausing profile of AD by linking pauses to the syntactic positions in which they appear and disease progression. MethodsSpeech was obtained through a picture description task, thus minimizing demands on episodic memory (EM), from a group of mild (N = 21) and moderate AD (N = 19), and healthy elderly controls (N = 40). Pauses were sub-indexed according to whether they occurred within-clauses, clause-initially, or utterance-initially, and whether they preceded nouns, verbs, or adjectives/adverbs, when occurring within-clauses. Additionally, relations to verbal fluency (VF) measures at the single-word level were explored. ResultsPause rate but not duration distinguished controls from both AD groups, while fillers did not distinguish any groups. The analysis by syntactic position revealed a highly differentiated picture, with largest effect sizes of significant group differences seen in the utterance-initial pause rate. The two AD groups patterned differently when compared to controls, while none of the measures differentiated the AD groups. Specifically, moderate but not mild AD differed from controls in clause-initial pauses, while mild but not moderate AD differed from controls in within-clause positions. At the within-clause level, the effect dividing controls from mild-AD was specifically driven by pauses ahead of nouns. A significant negative correlation emerged between pausing rate in spontaneous speech and VF measures in the mild-AD group only. ConclusionsIncreased empty (non-filled) pauses in AD are not confined to pauses in within-clause positions, which are most directly related to problems in the retrieval of words. Even in early disease stages, where these within-clause pause effects are seen, they are confined to nouns, revealing a grammatically specific problem possibly related to the referencing of objects. At all disease stages, pauses increase in utterance-sized units of structure, indicating progressive problems in the creative configuration of complete thoughts.

Verbal fluency difficulties in aphasia: A combination of lexical and executive control deficits.

BackgroundVerbal fluency tasks are routinely used in clinical assessment and research studies of aphasia. People with aphasia produce fewer items in verbal fluency tasks. It remains unclear if their output is limited solely by their lexical difficulties and/or has a basis in their executive control abilities. Recent research has illustrated that detailed characterization of verbal fluency performance using temporal characteristics of words retrieved, clustering and switching, and pause durations, along with separate measures of executive control stands to inform our understanding of the lexical and cognitive underpinnings of verbal fluency in aphasia.AimsTo determine the locus of the verbal fluency difficulties in aphasia, we compared semantic and letter fluency trials between people with aphasia and healthy control participants using a wide range of variables to capture the performance between the two groups. The groups were also tested on separate measures of executive control to determine the relationship amongst these tasks and fluency performance.Methods & ProceduresSemantic (animal) and letter (F, A, S) fluency data for 60s trials were collected from 14 people with aphasia (PWA) and 24 healthy adult controls (HC). Variables, such as number of correct responses, clustering and switching analyses, were performed along with temporal measures of the retrieved words (response latencies) and pause durations. Participants performed executive control tasks to measure inhibitory control, mental‐set shifting and memory span.Outcomes & ResultsCompared with HC, PWA produced fewer correct responses, showed greater difficulty with the letter fluency condition, were slower in getting started with the trials, showed slower retrieval times as noted in within‐ and between‐cluster pause durations, and switched less often. Despite these retrieval difficulties, PWA showed a similar decline in the rate of recall to HC, and had similar cluster size. Executive control measures correlated primarily with the letter fluency variables: mostly for PWA and in one instance for HC.Conclusions & ImplicationsPoorer performance for PWA is a combination of difficulties in both the lexical and executive components of the verbal fluency task. Our findings highlight the importance of detailed characterization of fluency performance in deciphering the underlying mechanism of retrieval difficulties in aphasia, and illustrate the importance of using letter fluency trials to tap into executive control processes.WHAT THIS PAPER ADDSWhat is already known on the subject PWA typically show impaired performance in verbal fluency tasks. It is debated whether this impaired performance is a result of their lexical difficulties or executive control difficulties, or a combination of both. This debate continues because previous studies have mostly used semantic fluency condition without including letter fluency condition; used a limited range of variables (e.g., number of correct responses); and not included separate executive control measures to explain the performance pattern in aphasia. This research addresses these outstanding issues to determine the specific contribution of lexical and executive control processes in verbal fluency in aphasia by including: both semantic and letter fluency conditions; a wide range of variables to identify the relative contribution of lexical and executive control mechanisms; and independent measures of executive control. What this paper adds to existing knowledge Using the multidimensional analysis approach for verbal fluency performance from both semantic and letter fluency conditions, this is the first study to systematically demonstrate that PWA had difficulties in both lexical and executive control components of the task. At the individual level, PWA had greater difficulty on the letter fluency condition compared with semantic fluency. We observed significant correlations between the executive control measures and verbal fluency measures primarily for the letter fluency condition. This research makes a significant contribution to our understanding of lexical and executive control aspects in word production in aphasia. What are the potential or actual clinical implications of this work? From a clinical perspective, this research highlights the importance of using a full range of verbal fluency and executive control measures to tap into the lexical as well as executive control abilities of PWA, and also the utility of using letter fluency to tap into the executive control processes in PWA.

Phenotypic subtypes of progressive dysexecutive syndrome due to Alzheimer's disease: a series of clinical cases.

Diagnostic criteria for a progressive dysexecutive syndrome due to Alzheimer's disease (dAD) were proposed. Clinical observations suggest substantial variability in the clinico-radiological profiles within this syndrome. We report a case series of 6 patients with dAD highlighting this heterogeneity. Average age at diagnosis was 57.3years, and patients were followed annually with clinical, cognitive, and multimodal imaging assessments for an average of 3.7years. Cases were divided based into three subtypes based on their pattern of FDG-PET hypometabolism: predominantly left parieto-frontal (ldAD), predominantly right parieto-frontal (rdAD), or predominantly biparietal (bpdAD) (n = 2 for each). Prominent executive dysfunction was evidenced in all patients. ldAD cases showed greater impairment on measures of verbal working memory and verbal fluency compared to other subtypes. rdAD cases showed more severe alterations in measures of visual abilities compared to language-related domains and committed more perseverative errors on a measure of cognitive flexibility. bpdAD cases presented with predominant cognitive flexibility and inhibition impairment with relative sparing of working memory and a slower rate of clinical progression. rdAD and bpdAD patients developed neuropsychiatric symptoms, whereas none of the ldAD patients did. For each subtype, patterns of tau deposition relatively corresponded to the spatial pattern of FDG hypometabolism. dAD cases could be differentiated from two clinical cases of atypical AD variants (language and visual) in terms of clinical, cognitive and neuroimaging profiles, suggesting that dAD subtypes represent clinical entities separable from other variants of the disease. The recognition of distinct dAD phenotypes has clinical relevance for diagnosis, prognosis, and symptom management.

An overactive mind: Investigating racing thoughts in ADHD, hypomania and comorbid ADHD and bipolar disorder via verbal fluency tasks

BackgroundAdults with Attention Deficit Hyperactivity Disorder (ADHD) often report mental restlessness akin to racing thoughts found in hypomanic and mixed episodes of bipolar disorder (BD). Past research has suggested that racing thoughts in BD can be tackled via process-oriented verbal fluency measures. In ADHD, it is still unknown whether racing thoughts is due to comorbid BD, and its neuropsychological underpinnings remain to be investigated. To this aim, this study investigates process-oriented verbal fluency measures in adults with ADHD compared to adults with BD in a hypomanic episode, adults with ADHD + BD and healthy controls. MethodsThree verbal fluency tasks, i.e., the free, the letter and the semantic conditions, were administered to 37 adults with ADHD, 25 adults with BD in a hypomanic episode, 22 adults with comorbid ADHD + BD (euthymia) and 31 healthy subjects. Word production, clustering, and switching were analysed in verbal fluency tasks. ResultsAdults with ADHD, ADHD + BD and hypomania showed increased switches in the free verbal fluency task, compared to healthy controls, despite equivalent number of words produced. Unlike the ADHD and ADHD + BD groups, phonological clustering measures in the semantic task were increased in the hypomanic group compared to healthy controls. LimitationsBD groups were under medication. ConclusionsSemantic overactivation, reflected by increased switches in the unconstrained verbal fluency task, appear to be a common mechanism involved in racing thoughts in both ADHD and BD. By contrast, unusual sounds-based associations are specific of hypomanic speech and might contribute to the distinction trait and state racing thoughts.

Utility of combined plasma amyloid beta 40, amyloid beta 42, total tau, and NfL along with a measure of cognitive functioning in detecting cognitive impairment among Hispanic, Mexican Americans compared to non‐Hispanic whites

AbstractBackgroundThe AT(N) diagnostic framework for Alzheimer’s Disease (AD) highlights the importance of specific plasma biomarkers associated with neurodegeneration (Amyloid Beta, Tau) and neuronal injury (Neurofilament light chain [Nf‐L]). Despite a wealth of research on such plasma biomarkers of AD pathology, limited work has specifically been conducted among minority populations. Our study sought to examine a combination of AD biomarkers both alone and in combination with a select measure of cognition among Hispanic, Mexican Americans (MA) and Non‐Hispanics Whites (NHW) in detecting cognitive impairment.MethodPlasma samples were assayed on n=1703 participants (n= 890 MA [n=676 Normal Cognition [NC]; n=214 Cognitively Impaired [CI]]; n= 813 NHW [n=673 NC; n=140 CI]) enrolled in a study of health disparities. Plasma Amyloid Beta 40, Amyloid Beta 42, Total Tau, and Nf‐L were assayed using Simoa. A measure of verbal fluency (FAS) was utilized. The samples were randomly split (70/30) to allow for a training and test set. Random Forest (RF) models were conducted with performance on the test set reported.ResultAmong MA, AD biomarkers alone produced an area under the curve (AUC) of 0.50 with a sensitivity (SN) of 0.77 and specificity (SP) of 0.17. When the AD biomarkers were included along with a measure of verbal fluency (FAS)(biomarker‐cognitive profile), AUC increased to 0.63 with an SN of 0.82 and SP of 0.17. Inclusion of demographics (age, gender, education) to the biomarker‐cognitive profile increased only SP, which reached 0.50. Among NHW, AD biomarkers alone produced an AUC of 0.35 with SN of 0.88 and SP of 0.74. The combined biomarker‐cognitive profile increased AUC to 0.66 with an SN of 0.42 and SP of 0.81. The addition of demographics further increased AUC to 0.72 (SN=0.53; SP=0.88).ConclusionDetection accuracy differed by ethnicity with a broader range shown among NHW (AUCs 0.35‐0.72) compared to MA (AUCs 0.50‐0.63). Utility of AD plasma biomarkers improved with the addition of a select cognitive measure. This is consistent with prior work showing the application of a combined model (biomarker‐cognitive profile) to distinguish those with cognitive impairment. The addition of demographic factors improved the detection only for NHW.

Hal, do I have memory problems? A pilot study investigating a voice recognition cognitive screening tool for detection of neuropsychological changes

AbstractBackgroundThe prevalence of mild, age‐advanced changes in cognition, defined as mild cognitive impairment, is spiking as the baby boomer population ages. Early and accurate detection of age‐advanced changes in thinking abilities leads to proper care, efficient use of resources, and promotion of research. Indeed, government based health care systems and insurance programs incentivize routine neurocognitive assessment. Brief, paper and pencil cognitive screeners such as the MMSE and MOCA are widely utilized in clinical settings. Such screeners lack sensitivity to subtle cognitive change and specificity related to the cause of decline. Moreover, administration and interpretation of these screeners is time consuming in a busy, clinical setting. Prior research has determined that electronic‐based testing is effective in detecting cognitive change (Zygouris &amp; Tsolaki, 2014). This pilot study aimed to investigate a convenient, platform agnostic, voice‐recognition screening tool for detection of mild, age‐advanced neurocognitive problems.MethodParticipants (n=16) were recruited from a large community‐based neurology practice, who underwent a comprehensive neuropsychological (NP) evaluation as part of their standard of care. Participants were administered an auditory list learning/recall test and a verbal fluency test (F/A/S and animals) via a voice recognition cognitive screening tool. Pearson correlations were conducted to examine the concurrent validity between the standard NP measures and those obtained using the current screening tool.ResultPreliminary data suggests a positive correlation between standard NP measures and those obtained using voice recording and speech recognition technologies; language: F/A/S (r = .716, p &lt; .005), animals (r .810, p &lt; .005); memory: delayed recall (r = .515, p &lt; .05).ConclusionThis pilot study demonstrated concurrent validity between standard NP measures of memory and verbal fluency and those obtained using a novel, voice recording and speech recognition screening tool. These initial data provide support for the efficacy of a computerized based screening tool for older adults. Such a screening too has the potential to maximize utilization across multiple settings (e.g., medical office, hospital, in‐home) and improve early detection of cognitive decline.

Qualitative Deficits in Verbal Fluency in Parkinson's Disease with Mild Cognitive Impairment: A Clinical and Neuroimaging Study.

Mild cognitive impairment (MCI) in Parkinson's disease (PD) is considered a risk factor for PD with dementia (PDD). Verbal fluency tasks are widely used to assess executive function in PDD. However, in cases of PD with MCI (PD-MCI), the relative diagnostic accuracy of different qualitative verbal fluency measures and their related neural mechanisms remain unknown. This study aimed to investigate the relative diagnostic accuracy of qualitative (clustering and switching) verbal fluency strategies and their correlates with functional imaging in PD-MCI. Forty-five patients with PD (26 with MCI and 19 without MCI) and 25 healthy controls underwent comprehensive neurocognitive testing and resting-state functional magnetic resonance imaging. MCI in patients with PD was diagnosed according to established clinical criteria. The diagnostic accuracy of verbal fluency measures was determined via receiver operating characteristic analysis. Changes in brain functional connectivity between groups and across clinical measures were assessed using seed-to-voxel analyses. Patients with PD-MCI generated fewer words and switched less frequently in semantic and phonemic fluency tasks compared to other groups. Switching in semantic fluency showed high diagnostic accuracy for PD-MCI and was associated with reduced functional connectivity in the salience network. Our results indicate that reduced switching in semantic fluency tasks is a sensitive and specific marker for PD-MCI. Qualitative verbal fluency deficits and salience network dysfunction represent early clinical changes observed in PD-MCI.