Impaired Semantic Fluency Research Articles

OS08.5.A UNDERSTANDING THE ASSOCIATION BETWEEN FATIGUE AND COGNITION IN GLIOMA PATIENTS: AN OBSERVATIONAL MULTINATIONAL STUDY

Abstract BACKGROUND Both fatigue and cognitive impairment are highly prevalent in individuals with glioma and have been associated with diminished health-related quality of life. Although the two are thought to be related, evidence remains sparse, in part, due to the limited availability of data. Therefore, we aimed to investigate the relationship between fatigue and cognition in adult glioma patients. MATERIAL AND METHODS We analyzed cognitive data from adult patients with diffuse glioma at the University of California San Francisco (UCSF, n=100) and Amsterdam UMC (n=127). Comparable cognitive tests were combined by domain: attention, information processing, mental flexibility, semantic fluency, verbal learning, verbal memory, and visual search. Z-scores of ≤ -1.5 SD were considered impaired. Fatigue was assessed with the Fatigue Symptom Inventory (UCSF) and the Checklist Individual Strength (Amsterdam UMC). Linear mixed models were used to assess associations between cognitive domains and fatigue adjusted for site, grade, histology, sex, radiotherapy, and chemotherapy. Latent profile analysis was used to identify distinct fatigue-cognitive phenotypes. RESULTS UCSF patients were older (50.3 vs. 44.9 years, p=0.002), more likely to have grade 4 tumors (32% vs. 18%, p=0.025), and more years since diagnosis (2.72 vs 1.27, p<0.001). Interestingly, though UCSF patients were more impaired across nearly all cognitive domains, there was no difference in fatigue between institutions (-0.0457 vs. -0.178, p=0.60). Attention and impaired semantic fluency were associated with fatigue severity in univariate models. Using backward selection, the best-fit model included only impaired semantic fluency (estimated effect = 0.35, p= 0.014, r2=0.03). We identified four distinct cognitive phenotypes in the pooled dataset, which validated across sites, though fatigue severity did not contribute to these phenotypes. CONCLUSION Although fatigue and cognitive symptoms can overlap, the association between cognitive impairment and fatigue severity is weak. Interestingly, this important finding was validated across institutions and glioma subtypes. Further study is needed to address questions regarding the longitudinal change of symptoms. Given the limited relational overlap, fatigue and cognitive impairments should both be explicitly assessed and treated with targeted therapies. SUPPORT/DISCLOSURE Stichting Anita Veldman Foundation CCA-2019-2-21; Amsterdam University Fund 4056-2022-7-8; CCA travel grant 2022-10-10; Prins Bernhard Cultuurfondsbeurs 40042576/NOD; R.A. Laan fonds 2022-10-24; The loglio Collective; Sheri Sobrato Brisson Brain Cancer Survivorship Program.

Poor physical fitness is associated with impaired memory, executive function, and depression in institutionalized older adults: a cross-sectional study

Objective:To analyze the association between physical fitness, cognitive function, and depressive symptoms among older adults in long-term care facilities (LTCFs).Methods:Seventy-six institutionalized male and female elderly individuals (65 years and older) living in LTCFs participated of this study. Physical fitness (aerobic capacity and strength), cognitive functions (global cognition, short-term and working and semantic memories, and executive function), and depressive symptoms were assessed. Linear regression and contingency analyses were performed. Significance was accepted at p-values ≤ 0.05.Results:Aerobic capacity predicted 32% of variance in global cognition (p < 0.01) and 25% of variance in semantic fluency/executive function (p < 0.01). Low levels of upper limb strength, lower limb strength, and aerobic capacity were associated with semantic fluency/executive function (OR = 1.38, p = 0.01, OR = 1.26, p = 0.03, and OR = 1.07, p = 0.01, respectively) and depressive symptoms (OR = 1.06, p < 0.01).Conclusion:Poor physical fitness is associated with cognition and depressive symptoms in institutionalized older adults. Low levels of strength and aerobic fitness increase the odds of presenting with impaired semantic fluency and executive function, possibly denoting an increased risk of developing dementia.

Impaired semantic memory during acute transient global amnesia.

As a clinical model of hippocampal dysfunction, transient global amnesia (TGA) causes reversible memory disturbance. While episodic memory deficits in TGA patients have been extensively described, data regarding semantic memory involvement are sparse and contradictory. We report impaired semantic fluency performance in 16 patients with hippocampal lesions on MRI during acute TGA compared to their performance one day later and to that of 20 healthy subjects. Our findings support the involvement of the hippocampus in semantic retrieval.

Effects of White Matter Hyperintensities on Verbal Fluency in Healthy Older Adults and MCI/AD.

BackgroundWhite matter hyperintensities (WMHs) are markers for cerebrovascular pathology, which are frequently seen in patients with mild cognitive impairment (MCI) and Alzheimer’s disease (AD). Verbal fluency is often impaired especially in AD, but little research has been conducted concerning the specific effects of WMH on verbal fluency in MCI and AD.ObjectiveOur aim was to examine the relationship between WMH and verbal fluency in healthy old age and pathological aging (MCI/AD) using quantified MRI data.MethodsMeasures for semantic and phonemic fluency as well as quantified MRI imaging data from a sample of 42 cognitively healthy older adults and 44 patients with MCI/AD (total n = 86) were utilized. Analyses were performed both using the total sample that contained seven left-handed/ambidextrous participants, as well with a sample containing only right-handed participants (n = 79) in order to guard against possible confounding effects regarding language lateralization.ResultsAfter controlling for age and education and adjusting for multiple correction, WMH in the bilateral frontal and parieto-occipital areas as well as the right temporal area were associated with semantic fluency in cognitively healthy and MCI/AD patients but only in the models containing solely right-handed participants.ConclusionThe results indicate that white matter pathology in both frontal and parieto-occipital cerebral areas may have associations with impaired semantic fluency in right-handed older adults. However, elevated levels of WMH do not seem to be associated with cumulative effects on verbal fluency impairment in patients with MCI or AD. Further studies on the subject are needed.

Regional neuropathology distribution and verbal fluency impairments in Parkinson's disease

BackgroundVerbal fluency deficits are common in patients with Parkinson's disease. The association of these impairments with regional neuropathological changes is unexplored. ObjectivesDetermine if patients with verbal fluency impairments have greater neuropathological burden in frontal, temporal, and limbic regions and if Lewy bodies or neurofibrillary tangles were associated with verbal fluency impairments. MethodsData was derived from the Arizona Study of Aging and Neurodegenerative Disorders. 47 individuals who completed phonemic and semantic verbal fluency tasks and met clinicopathological criteria for Parkinson's disease (with and without comorbid Alzheimer's disease) were included. Impairment on fluency tasks was defined by normative data, and the density of neuropathology in temporal, limbic, and frontal regions was compared between groups. ResultsIndividuals with semantic fluency impairments had greater total pathology (Lewy bodies + neurofibrillary tangles) in limbic structures (W = 320.0, p = .033, rpb = .33), while those who had phonemic fluency impairments had increased total neuropathology in frontal (W = 364.5, p = .011, rpb = .37), temporal (W = 356.5, p = .022, rpb = .34), and limbic regions (W = 357.0, p = .024, rpb = .34). Greater Lewy body density was found in those with verbal fluency impairments, though trends for greater neurofibrillary tangle density were noted as well. ConclusionsImpaired phonemic fluency was associated with higher Lewy body and tangle burden in frontal, temporal, and limbic regions, while impaired semantic fluency was associated with greater limbic pathology. Though neurofibrillary tangles trended higher in several regions in those with impaired verbal fluency, higher Lewy body density in general was associated with verbal fluency deficits. Implications for research and clinical practice are discussed.

Relation of lead trajectory and electrode position to neuropsychological outcomes of subthalamic neurostimulation in Parkinson’s disease: results from a randomized trial

Deep brain stimulation of the subthalamic nucleus improves motor functions in patients suffering from advanced Parkinson's disease but in some patients, it is also associated with a mild decline in cognitive functioning about one standard deviation from the preoperative state. We assessed the impact of the cortical lead entry point, the subcortical electrode path and the position of the active electrode contacts on neuropsychological changes after subthalamic nucleus-deep brain stimulation compared to a control group of patients receiving best medical treatment. Sixty-eight patients with advanced Parkinson's disease were randomly assigned to have subthalamic nucleus-deep brain stimulation or best medical treatment for Parkinson's disease. All patients had a blinded standardized neuropsychological exam (Mattis Dementia Rating scale, backward digit span, verbal fluency and Stroop task performance) at baseline and after 6 months of treatment. Patients with subthalamic nucleus-deep brain stimulation were defined as impaired according to a mild decline of one or more standard deviations compared to patients in the best medical treatment group. The cortical entry point of the electrodes, the electrode trajectories and the position of the active electrode contact were transferred into a normalized brain volume by an automated, non-linear registration algorithm to allow accurate statistical group analysis using pre- and postoperative magnetic resonance imaging data. Data of 31 patients of the subthalamic nucleus-deep brain stimulation group and 31 patients of the best medical treatment group were analysed. The subthalamic nucleus-deep brain stimulation group showed impaired semantic fluency compared with the best medical treatment group 6 months after surgery (P = 0.02). Electrode trajectories intersecting with caudate nuclei increased the risk of a decline in global cognition and working memory performance. Statistically, for every 0.1 ml overlap with a caudate nucleus, the odds for a decline >1 standard deviation increased by a factor of 37.4 (odds ratio, confidence interval 2.1-371.8) for the Mattis Dementia Rating Scale and by a factor of 8.8 (odds ratio, confidence interval 1.0-70.9) for the backward digit span task. Patients with subthalamic nucleus-deep brain stimulation who declined in semantic verbal fluency, Stroop task and the backward digit span task performance showed a position of the active electrode outside the volume built by the active electrodes of stable performers. Passage of the chronic stimulation lead through the head of the caudate increases the risk of global cognitive decline and working memory performance after subthalamic nucleus-deep brain stimulation in Parkinson's disease. Therefore the electrode path should be planned outside the caudate nuclei, whenever possible. This study also stresses the importance of precise positioning of the active stimulating contact within the subthalamic volume to avoid adverse effects on semantic verbal fluency and response inhibition.

Falls in Parkinson Disease: Analysis of a Large Cross-Sectional Cohort

Falls remain a significant cause of morbidity in PD. Risk factors are not well understood. In this study we explore risk factors for falls in PD utilizing the cross-sectional, baseline data in the National Parkinson Foundation Quality Improvement Initiative (NPF-QII) database. Subjects are being followed prospectively, and this study will provide the basis for subsequent longitudinal analyses. A cross-sectional analysis of data from 2,876 ambulatory patients with Parkinson disease enrolled in the NPF-QII at 18 sites. Main outcome measure was falling history in the 3 months preceding assessment. The following were considered as possible predictor variables: age, sex, height, weight, body mass index, disease duration, age at disease onset, investigator's confidence in the diagnosis, Hoehn and Yahr stage, rest tremor, ability to stand unassisted, coexistent pathologies (cardiovascular, respiratory, diabetes, cancer, neurological, osteoarthritis, and "other" comorbidities), anticholinergics, antidepressants, antipsychotics, cognitive enhancers, deep brain stimulation surgery, timed-up-and-go, semantic fluency, and 5 word recall. Variables with associations to the outcome measure in univariate analyses were analyzed in multivariable models using logistic regression. 37.2% of subjects experienced falls. In the multivariable regression model the following variables were found to be independently associated with falls: disease duration; Hoehn and Yahr stage; absence of rest tremor; cardiovascular, arthritis, or "other" comorbidity; antidepressants; deep brain stimulation surgery; timed-up-and-go; and, semantic fluency. Disease duration but not age is independently associated with falls in Parkinson disease. Timed-up-and-go accurately reflects falls risk. Impaired semantic fluency is independently associated with falls, while verbal memory is not. Comorbidities, antidepressants, and deep brain stimulation also contribute to falls risk.

Fewer Paris, parrots peaches: Interpreting cross-cultural semantic fluency deficits in Alzheimer's assessment

Impaired semantic fluency has emerged as a robust neuropsychological indicator of Alzheimer's Disease (AD). Furthermore, semantic fluency deteriorates more rapidly than phonemic fluency and this discrepancy pattern is thought to be especially useful in the early assessment and differential diagnosis of AD. However, studies have implicated a role for culture in semantic task performance suggesting that certain cognitive processes are facilitated by cultural knowledge and the country's state of development. Since 60% of AD patients are estimated to come from developing countries, the implications of these assertions with respect to the interpretation of cognitive performance are crucial to valid AD assessment. The effects of age, education and ethnicity on performance on semantic (cities, animals, fruits) and phonemic (letters P, F, L) verbal fluency were investigated using multiple regression analyses in 124 healthy British and Caribbean adults. Caribbean and British persons had similar scores on phonemic fluency for all three letters (P, F, L). However, the Caribbean group produced significantly fewer words for each semantic category (cities, animals, fruits). Increasing years of education were associated with greater word production in both semantic and phonemic fluency. There was no interaction between ethnicity and education or age. The phonemic-semantic fluency scores in Caribbean's fall within the range of normal performance but the discrepancy between the two scores parallels the pattern observed in impaired AD patients. These results provide further psychometric substantiation for different cognitive processes being involved in phonemic versus semantic fluency. Lower word production in semantic fluency in the Caribbean group may be attributed to differences in societal development and access to education, both of which shape and facilitate abstraction, categorical and taxonomic thinking skills that are required for semantic fluency, but not for phonemic fluency. The findings also suggest that these cognitive skills may not be invariably present but are differentially influenced by culture. These skills are measured in semantic fluency and may be featured in routine neuropsychological assessment of AD. Differences in cognitive performance which are attributable to culture and not AD pathology has critical implications for valid AD assessment both within and across cultures.

Parkinson’s disease II: longitudinal progression, development of dementia and new gene therapy

As mentioned in last month’s Journal Club, a plethora of articles in various fields of Parkinson’s disease are published every month. In this edition of the Journal Club, another three of them will be presented. In the first, an 8-year follow-up study, the longitudinal progression of sporadic Parkinson’s disease was evaluated by multi-tracer positron emission tomography. This study confirms the previously described ‘‘caudate to putamen gradient’’ (with the caudate less affected than the putamen) and stresses that different factors might be involved in disease initiation and disease progression. The second study—also a longterm follow-up—focuses on cognitive impairment in Parkinson’s disease. It identifies three clinical factors and one genetic factor which have a highly predictive value for the risk of development of dementia in Parkinson’s disease: first, age above 72 years, second, impaired semantic fluency and third, inability to copy an intersecting pentagons figure; the major genetic predictor of dementia risk in Parkinson’s disease is evidently the so-called H1/H1 genotype of the gene coding for the microtubule-associated protein tau. In the third study, the safety, tolerability and efficacy of putaminal aromatic L-amino acid decarboxylase (AADC) gene therapy for Parkinson’s disease was evaluated in two small cohorts. This study shows on the one hand a clinical benefit and on the other a considerable risk of intracranial hemorrhage due to the surgical procedure. Longitudinal progression of sporadic Parkinson’s disease: a multi-tracer positron emission tomography study

Topics in Sem Anesth

Impairments of verbal fluency are recognised in adult-onset schizophrenia but their presence in early-onset schizophrenia is not well established. This study investigated the extent and character of verbal fluency disturbance in young patients close to illness onset. Thirty-three adolescents with DSM-IV schizophrenia and 33 controls completed phonemic and semantic fluency tests and a free design fluency test. Patients had significantly impaired semantic fluency compared to controls but no impairment on phonemic or design fluency. The difference between patients and controls for semantic fluency remained significant when corrected for age and IQ. These results lend support to the hypothesis that impaired semantic fluency may be an early trait marker of schizophrenia that is potentially related to a failure of lateralisation of language.

Semantic fluency is impaired but phonemic and design fluency are preserved in early-onset schizophrenia

Impairments of verbal fluency are recognised in adult-onset schizophrenia but their presence in early-onset schizophrenia is not well established. This study investigated the extent and character of verbal fluency disturbance in young patients close to illness onset. Thirty-three adolescents with DSM-IV schizophrenia and 33 controls completed phonemic and semantic fluency tests and a free design fluency test. Patients had significantly impaired semantic fluency compared to controls but no impairment on phonemic or design fluency. The difference between patients and controls for semantic fluency remained significant when corrected for age and IQ. These results lend support to the hypothesis that impaired semantic fluency may be an early trait marker of schizophrenia that is potentially related to a failure of lateralisation of language.