Differential verbal fluency deficits in the preclinical stages of Alzheimer's disease and vascular dementia

We examined patterns of early and late word generation in category and letter fluency among persons in the preclinical stages of Alzheimer's disease (AD) and vascular dementia (VaD). The sample consisted of 20 preclinical VaD persons, 66 preclinical AD persons, and 267 control persons, sampled from the community. Persons in the preclinical phase of AD and VaD were similarly impaired in letter fluency, although the preclinical VaD group outperformed their AD counterparts in category fluency. This pattern of results is consistent with the notion that category fluency is relatively more dependent on the medial-temporal lobe, whereas letter fluency relies more on frontal regions. The patterns of fluency impairment in preclinical AD and VaD generalized across early and late word retrieval.     

Clustering and switching during a semantic verbal fluency test contribute to differential diagnosis of cognitive impairment

The verbal fluency test (VFT) can be dissociated into "clustering" (generating words within subcategories) and "switching" (shifting between clusters), which may be valuable in differential diagnosis. In the current study, we investigated the validity of VFT in the differential diagnosis of Alzheimer’s disease (AD, n = 65), vascular dementia (VaD, n = 65), mild cognitive impairment (MCI, n = 92), and vascular cognitive impairment without dementia (VCIND, n = 76) relative to cognitively normal senior controls (NC, n = 374). We found that in the NC group, the total correct score was significantly correlated with age and education; males generated more subcategories; cluster size increased with education, and subcategory and switching decreased with age. A significantly progressive advantage was observed in VFT scores in the sequence NC > MCI/VCIND > AD/VaD, and this significantly discriminated dementia patients from the other groups. AD patients performed better in all four VFT scores than VaD patients. Subcategory and switching scores significantly distinguished AD from VaD patients (AD > VaD; mean difference, 0.50 for subcategory, P <0.05; 0.71 for switching, P <0.05). MCI patients scored higher than VCIND patients, but the difference did not reach statistical significance. These results suggest that semantic VFT is useful for the detection of MCI and VCIND, and in the differential diagnosis of cognitive impairment.     

Dissociative semantic breakdown in Alzheimer's disease: Evidence from multiple category fluency test

Background

Category-specific semantic dissociation particularly in terms of biological and non-biological dichotomy has been described in Alzheimer's disease (AD). We re-examine above finding by performing multiple superordinate category verbal fluency test in AD patients.

Method

We analyze the baseline neuropsychological assessment performance of food and animal fluency test of AD patients from a tertiary hospital that collected prospectively over 5 years period and correlation was calculated by Kappa test. The analysis is stratified according to literacy level (primary: 0–6 years education and secondary: >6 years education) and disease severity (MMSE score: mild 19-24, moderate 13-18 and severe <13).

Result

A total of 296 AD patients were analyzed and only fair to moderate agreement between food and animal category fluency test was found especially in the mild AD cases (primary: kappa 0.42; secondary: kappa 0.40). Kappa agreement level increases when disease progress especially in the secondary education group. Food category, which is a more relevant semantic knowledge to Singapore population, is generally more affected. Higher educated subjects appeared to have less semantic dissociation effect when disease progress.

Conclusion

Despite less primed in daily life, biological category of semantic knowledge appears to be affected less during AD process in highly urbanized Singapore society. Brain appears to have special protective mechanism towards living things. However, education level seems have a modulation effect towards the biological protective mechanism.     

A longitudinal study of quantitative and qualitative features of category verbal fluency in incident Alzheimer's disease subjects: results from the PAQUID study

Category fluency tests were administered at baseline and after 3 and 5 years on two subgroups of subjects from a population-based cohort of elderly subjects: 52 cases of incident possible and probable Alzheimer's disease (AD) and 104 age- and education-matched subjects who remained nondemented. Quantitative and qualitative features of category fluency were assessed to determine how changes occur within 5 years of the diagnosis of AD. Consistent with previous results, we found that the number of words produced on this task was already significantly lower 5 years before the diagnosis in subjects with incident AD as compared with subjects who did not become demented. However, the rate of repetitions only significantly increased in AD subjects at the time of diagnosis, and the rate of intrusions remained low and not significantly different between the two groups. Thus, it is concluded that dysfunction in cognitive processes underlying repetitions and intrusions in verbal fluency tasks, such as inhibitory processes and working memory, may not be the main cause of the very early deficit in verbal fluency occurring in AD.     

Relationship between regional cerebral blood flow and verbal fluency in Alzheimer's disease

Category and letter verbal fluency tests are widely used for dementia detection and severity measure. Performances of these tasks have been regarded to be mainly associated with the left frontal lobe function. However, some recent studies suggest that there are different neuropsychological bases between these two tasks, and the brain region which contributes to these performances still remains unclear in Alzheimer's disease (AD). To clarify the neural basis of verbal fluency in AD, we examined the relationship between performances of these tasks and regional cerebral blood flow (rCBF). Twenty-five AD patients were administered verbal fluency tasks and single photon emission computed tomography (SPECT) scans. Thirteen cortical regions of interest were symmetrically defined in each hemisphere. Letter fluency scores were correlated significantly only with the left prefrontal (Brodmann's area (BA) 10-46) regional cerebral blood flow (rCBF). In contrast, category fluency scores were correlated most strongly with the left temporal rCBF and also with the left prefrontal (BA 10-46) rCBF. In conclusion, the present study suggests that left prefrontal (BA 10-46) dysfunction contributes to decline in both letter and category fluency scores in AD, while typical posterior dysfunction of AD has a closer relationship with decline in category fluency scores.     

Category fluency is also predominantly affected in Swiss Alzheimer's disease patients

Objectives – To establish the comparative efficacy to differentiate between Swiss patients with dementia of the Alzheimer type (DAT) and elderly normal control subjects (NC) on two different verbal fluency tasks: category fluency and letter fluency. Material and methods – Fifty Swiss German DAT patients in the early stages of the disease and 50 matched normal control subjects were compared on letter and category fluency tasks. Results – DAT patients exhibited an overproportional impairment on category fluency as compared with letter fluency. Receiver operating characteristic curves (ROC) showed that category fluency correctly classified a significantly higher number of DAT patients and NC subjects (84%) than letter fluency (70%). Conclusion – As similar findings have been described for English-speaking DAT patients, we conclude that deficiencies in category fluency are a general phenomenon, reflecting impaired structures of semantic knowledge occurring early in the course of Alzheimer's disease.     

The anatomical bases of semantic retrieval deficits in early Alzheimer's disease

Semantic abilities deteriorate early in patients with Alzheimer's disease (AD) and their residual language is characterised by strong lexical effects such as the age of acquisition of words and their typicality. The anatomical bases of this early semantic degradation have not been fully explored. To clarify which neural structures, when atrophic, alter lexical-semantic function in patients with very mild AD, this study correlated the lexical attributes of words produced in a semantic fluency task with grey matter density values from 3D MRI scans of mild AD patients. The voxel-based analyses showed a significant correlation between the lexical attributes characterising residual linguistic production in early AD patients and the integrity of regions of the medial temporal lobes, especially in areas of the perirhinal and parahippocampal cortex. This correlation was present in both hemispheres. There were no correlations within these structures with scores on neuropsychological tests not involving semantic or episodic memory. The results have implications for the role of medial temporal structures in episodic and semantic retrieval and argue against a unitary function of these structures in respect of episodic and semantic memory processes. This evidence suggests that specialised regions within the hippocampal complex engage in processes of encoding and retrieval for both semantic and episodic memories.     

Mental health symptoms and verbal fluency in elderly people: Evidence from the Spanish longitudinal study of aging

Objectives: Depression and loneliness are highly prevalent in old age. Moreover these mental health symptoms adversely affect the verbal fluency of the elderly. We examined the relationship between depression and loneliness with verbal fluency in people aged 50 years or older.

Method: Research data were collected during the pilot study of the Longitudinal Aging Study in Spain (ELES) in which a representative sample of non-institutionalized Spanish older people was assessed. Here, the cross-sectional data for 962 participants were analysed using hierarchical regressions, controlling for age, education level, overall cognitive functioning, social networks and satisfaction with family.

Results: Higher levels of cognitive functioning were associated with higher verbal fluency. Females showed higher levels of phonological fluency. Neither depression nor loneliness were significant predictors of phonological fluency but loneliness was a significant predictor of semantic fluency. For mild levels of loneliness, the rate of decline in semantic fluency slows in the oldest ages. In contrast, for severe loneliness the rate of decline in semantic fluency increases in the oldest ages.

Conclusions: Depressive symptoms, loneliness and cognitive impairment are all prominent in ageing and therefore their impact on ageing needs to be better understood. Early detection of loneliness, along with the implementation of intervention for individuals diagnosed with loneliness is advisable in order to avoid negative repercussions for the verbal fluency of these individuals.     

Analysis of young children’s abilities to cluster and switch during a verbal fluency task

To investigate developmental changes that take place in verbal fluency (VF) performance during early childhood, a VF task was administered to 225 healthy, Dutch-speaking children aged between 4.14 and 6.89 years. Three categories of VF outcome measures were included: i.e., word productivity, mean cluster size, and number of switches. Age influenced performance on all VF outcome measures linearly; i.e., older children produced more words, made longer clusters, and switched more. Higher levels of intelligence were associated with increased VF word productivity, but not with measures of switching and clustering. When leaving intelligence out of these analyses, we additionally found an interaction between level of parental education (LPE) and sex on total word productivity, i.e., girls with parents who had lower LPE produced fewer words than the other children. Furthermore, a similar interaction of LPE and sex was found for the number of switches: i.e., girls who had parents with lower LPE made fewer switches than the other children. Findings suggest that even in 4 to 6-year-old children important changes take place over time in VF and in processes underlying successful performance. Attention should be paid to age-extrinsic factors, such as LPE and sex, since these have been found to influence VF performance in young children.     

Recurrent perseverations on semantic verbal fluency tasks as an early marker of cognitive impairment

Introduction: Our objective was to examine the association between perseverations produced on the semantic verbal fluency (SVF) task in asymptomatic individuals and the future diagnosis of cognitive impairment (CI).

Method: Participants were individuals participating in the Mayo Clinic Study of Aging (N = 1269, M_age = 79.3 years, SD = 5.1; 51% men). All were cognitively normal at baseline and were followed in 15-month intervals for up to 6 visits. Each neurocognitive assessment included SVF tasks (“animals,” “fruits,” and “vegetables”). Cox modeling was used to test for associations between perseverations and time to CI diagnosis.

Results: Perseverations on the “animals” SVF task were associated with incident CI (hazard ratio = 1.35; 95% confidence interval, CI [1.10, 1.66]). No significant association was found with perseverations on the “fruits” or “vegetables” SVF tasks. Mixed-effects modeling in cognitively normal participants revealed that the number of perseverations at baseline is significantly associated with decline in memory and visuospatial cognitive domains but is not associated with decline in attention.

Conclusions: Assessing perseverations together with standard SVF scores on the “animals” SVF task can help in early identification of asymptomatic individuals at an increased risk for CI. Perseverations are not associated with attention, but rather visual and verbal working memory mechanisms. In longitudinal settings aimed at early detection of signs of CI in presymptomatic individuals, SVF testing with scoring that includes counting of perseverations may potentially serve as a practical alternative to the more cumbersome memory tests.     

Action fluency in Parkinson's disease: a follow-up study.

The impairment in action fluency task present in Parkinson's disease (PD) patients has been previously interpreted as an indicator of conversion from PD to PD with dementia or as a grammatical deficit for verbs and ascribed to a frontostriatal loop pathophysiology. In the present study, 20 patients with PD without dementia were longitudinally tested with overall cognitive decline scales and semantic, letter, and action fluency tasks in a 24-month follow-up study. In comparison with healthy age-matched controls, PD patients showed a stable and consistent impairment on action fluency without any sign of cognitive decline. Our findings suggest that action fluency task may be an early sign of impairment of frontostriatal circuits in PD and it cannot be considered an indicator of conversion from PD to PD with dementia.     

Cut the coda: early fluency intervals predict diagnoses

The aim of this study was threefold: (i) to clarify whether letter and category fluency tap different cognitive abilities; (ii) to make diagnostic comparisons and predictions using temporally resolved fluency data; (iii) to challenge and test the widely made assumption that 1-min sum scores are the fluency test measure of choice in the diagnosis of dementia. Scores from six 10-sec intervals of letter and category fluency tests were obtained from 240 participants including cognitive levels ranging from mild subjective cognitive complaints to Alzheimer's disease. Factor analysis revealed clearly separate factors corresponding to letter and category fluency. Category fluency was markedly impaired in Alzheimer's disease but not in Mild Cognitive Impairment. Only scores from relatively early intervals predicted Alzheimer's disease and Mild Cognitive Impairment. The conclusions are (i) letter and category fluency are different tests, category fluency being the best diagnostic predictor; (ii) it would be possible to administer category fluency tests only for 30 sec, because after this point the necessary differential diagnostic information about the patient's word fluency capacity has already been gathered.     

Category-specific semantic deficits in Alzheimer's disease: a semantic priming study

Category-specific semantic deficits in individuals suffering brain damage after relatively focal lesions provide an important source of evidence about the organization of semantic knowledge. However, whether Alzheimer's disease (AD), in which the brain damage is more widespread, affects semantic categories to a different extent is still controversial. In the present study, we assess this issue by means of the semantic priming technique. AD patients with a mild impairment of their semantic knowledge showed comparable priming effects to that of controls for the categories of animals and artifacts. Interestingly, however, patients with a moderate impairment of their semantic knowledge showed a normal priming effect for animals but a very reduced priming effect (if any) for artifacts. These results reveal that AD may affect the semantic knowledge of different semantic categories to a different extent. The implications of this observation for current theoretical accounts of semantic representation in the brain are discussed.     

Conceptual fluency at test shifts recognition response bias in Alzheimer's disease: implications for increased false recognition

The presence or absence of conceptual information in pictorial stimuli may explain the mixed findings of previous studies of false recognition in patients with mild Alzheimer's disease (AD). To test this hypothesis, 48 patients with AD were compared to 48 healthy older adults on a recognition task first described by Koutstaal et al. [Koutstaal, W., Reddy, C., Jackson, E. M., Prince, S., Cendan, D. L., & Schacter D. L. (2003). False recognition of abstract versus common objects in older and younger adults: Testing the semantic categorization account. Journal of Experimental Psychology: Learning, Memory, and Cognition, 29, 499-510]. Participants studied and were tested on their memory for categorized ambiguous pictures of common objects. The presence of conceptual information at study and/or test was manipulated by providing or withholding disambiguating semantic labels. Analyses focused on testing two competing theories. The semantic encoding hypothesis, which posits that the inter-item perceptual details are not encoded by AD patients when conceptual information is present in the stimuli, was not supported by the findings. In contrast, the conceptual fluency hypothesis was supported. Enhanced conceptual fluency at test dramatically shifted AD patients to a more liberal response bias, raising their false recognition. These results suggest that patients with AD rely on the fluency of test items in making recognition memory decisions. We speculate that AD patients' over reliance upon fluency may be attributable to (1) dysfunction of the hippocampus, disrupting recollection, and/or (2) dysfunction of prefrontal cortex, disrupting post-retrieval processes.     

A gamma band specific role of the subthalamic nucleus in switching during verbal fluency tasks in Parkinson's disease

Objective

Decline in verbal fluency is the most consistent and persistent cognitive impairment documented after deep brain stimulation of the subthalamic nucleus in Parkinson's disease. The mechanisms of this deficit are unclear. We aimed to identify and characterise verbal fluency related processing within the subthalamic nucleus through analysis of local field potentials.

Methods

Local field potentials were recorded from deep brain stimulation electrodes implanted in the subthalamic nuclei of 8 patients (16 sides) with Parkinson's disease, when patients were on medication. Patients performed phonemic and semantic verbal fluency tasks and a control word repetition task to control for the motor output involved in response generation.

Results

Significant increases in local field potential Power (p ≤ 0.05) were seen across a broad gamma frequency band (30–95 Hz) during both verbal fluency tasks, after controlling for motor output. Increases in gamma local field potential Power of + 7.5% ± 2.3% (SEM) in the semantic fluency task and + 6.9% ± 2.0% in the phonemic fluency task were derived when averaging across all electrode contact pairs. Gamma changes recorded from contacts lying in the left hemisphere (dominant in verbal fluency) correlated with average number of correct responses generated (r = 0.81 p = 0.015) and measures of ‘switching’ (r = 0.79 p = 0.020) particularly strongly in the semantic fluency task.

Interpretation

Frequency specific power changes observed during task performance are consistent with involvement of the subthalamic nucleus in switching during verbal fluency. Antagonism of such task-related activity with high frequency stimulation of this nucleus may explain the impairments reported.     

Impaired semantic knowledge underlies the reduced verbal short-term storage capacity in Alzheimer's disease

A decrease in verbal short-term memory (STM) capacity is consistently observed in patients with Alzheimer's disease (AD). Although this impairment has been mainly attributed to attentional deficits during encoding and maintenance, the progressive deterioration of semantic knowledge in early stages of AD may also be an important determinant of poor STM performance. The aim of this study was to examine the influence of semantic knowledge on verbal short-term memory storage capacity in normal aging and in AD by exploring the impact of word imageability on STM performance. Sixteen patients suffering from mild AD, 16 healthy elderly subjects and 16 young subjects performed an immediate serial recall task using word lists containing high or low imageability words. All participant groups recalled more high imageability words than low imageability words, but the effect of word imageability on verbal STM was greater in AD patients than in both the young and the elderly control groups. More precisely, AD patients showed a marked decrease in STM performance when presented with lists of low imageability words, whereas recall of high imageability words was relatively well preserved. Furthermore, AD patients displayed an abnormal proportion of phonological errors in the low imageability condition. Overall, these results indicate that the support of semantic knowledge on STM performance was impaired for lists of low imageability words in AD patients. More generally, these findings suggest that the deterioration of semantic knowledge is partly responsible for the poor verbal short-term storage capacity observed in AD.     

White matter tracts lesions and decline of verbal fluency after deep brain stimulation in Parkinson's disease

Decline of verbal fluency (VF) performance is one of the most systematically reported neuropsychological adverse effects after subthalamic nucleus deep brain stimulation (STN‐DBS). It has been suggested that this worsening of VF may be related to a microlesion due to the electrode trajectories. We describe the disruption of surrounding white matter tracts following electrode implantation in Parkinson's disease (PD) patients with STN‐DBS and assess whether damage of fiber pathways is associated with VF impairment after surgery. We retrospectively analyzed 48 PD patients undergoing bilateral STN DBS. The lesion mask along the electrode trajectory transformed into the MNI 152 coordinate system, was compared with white matter tract atlas in Tractotron software, which provides a probability and proportion of fibers disconnection. Combining tract‐ and atlas‐based analysis reveals that the trajectory of the electrodes intersected successively with the frontal aslant tract, anterior segment of arcuate tract, the long segment of arcuate tract, the inferior longitudinal fasciculus, the superior longitudinal fasciculus, the anterior thalamic radiation, and the fronto striatal tract. We found no association between the proportion fiber disconnection and the severity of VF impairment 6 months after surgery. Our findings demonstrated that microstructural injury associated with electrode trajectories involved white matter bundles implicated in VF networks.