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1.  On Which Abilities Are Category Fluency and Letter Fluency Grounded? A Confirmatory Factor Analysis of 53 Alzheimer's Dementia Patients 
In Alzheimer's dementia (AD), letter fluency is less impaired than category fluency. To check whether category fluency and letter fluency depend differently on semantics and attention, 53 mild AD patients were given animal and letter fluency tasks, two semantic tests (the Verbal Semantic Questionnaire and the BORB Association Match test), and two attentional tests (the Stroop Colour-Word Interference test and the Digit Cancellation test).
We conducted a LISREL confirmatory factor analysis to check the extent to which category fluency and letter fluency tasks were related to semantics and attention, viewed as latent variables.
Both types of fluency tasks were related to the latent variable Semantics but not to the latent variable Attention.
Our findings warn against interpreting the disproportionate impairment of AD patients on category and letter fluency as a contrast between semantics and attention.
PMCID: PMC3711000  PMID: 23885263
Language; Dementia; Verbal fluency; Semantics; Attention
2.  Initial letter and semantic category fluency in Alzheimer's disease, Huntington's disease, and progressive supranuclear palsy. 
Ten patients with dementia of Alzheimer's type, 10 patients with progressive supranuclear palsy, and 10 patients with Huntington's disease were compared on two types of verbal fluency task--namely, initial letter fluency and category (semantic) fluency. The groups were carefully matched for overall level of dementia on the dementia rating scale, and were compared with 25 age matched normal controls. The controls found letter fluency more difficult than category fluency, and this relative pattern of performance was repeated in the progressive supranuclear palsy and Huntington's disease groups, although both groups were significantly impaired on both tasks. By contrast, patients with Alzheimer's disease performed just as poorly as the progressive supranuclear palsy and Huntington's disease groups on the category tasks, but were significantly less impaired at letter fluency, performing at near normal levels on this task. From these results, it is suggested that the performances of patients with progressive supranuclear palsy and Huntington's disease relate largely to initiation and retrieval problems secondary to disruption of frontostriatal circuits, whereas in Alzheimer's disease, the poorer performance on category fluency is due principally to the breakdown of semantic knowledge, which probably reflects temporal neocortical involvement.
PMCID: PMC1073192  PMID: 7964817
3.  Non-Fluent Speech in Frontotemporal Lobar Degeneration 
Journal of neurolinguistics  2009;22(4):370-383.
We investigated the cognitive and neural bases of impaired speech fluency, a central feature of primary progressive aphasia. Speech fluency was assessed in 35 patients with frontotemporal lobar degeneration (FTLD) who presented with progressive non-fluent aphasia (PNFA, n=11), semantic dementia (SemD, n=12), or a social and executive disorder without aphasia (SOC/EXEC, n=12). Fluency was quantified as the number of words per minute in an extended, semi-structured speech sample. This was related to language characteristics of the speech sample and to neuropsychological measures. PNFA patients were significantly less fluent than controls and other FTLD patients. Fluency correlated with grammatical expression but not with speech errors or executive difficulty. SemD and SOC/EXEC patients were also less fluent than controls. In SemD, fluency was associated with semantically limited content. In SOC/EXEC, fluency was associated with executive limitations. Voxel-based morphometry analyses of high-resolution MRI related fluency to gray matter volume in left inferior frontal, insula, and superior temporal regions for the entire cohort of FTLD patients. This region overlapped partially distinct atrophic areas in each FTLD subgroup. It thus appears to play a crucial role in speech fluency, which can be interrupted in different ways in different FTLD subgroups.
PMCID: PMC3238501  PMID: 22180700
frontotemporal dementia; progressive aphasia; MRI; speech fluency
4.  Category and letter verbal fluency across the adult lifespan: relationship to EEG theta power 
The purpose of this study was to examine the impact of age, sex, and education on category and letter verbal fluency task performance. A secondary goal was to examine whether resting EEG theta power in bilateral frontal and temporal lobes impacts age-associated decline in verbal fluency task performance. A large sample (N=471) of healthy, normal participants, age 21–82, was assessed for letter fluency (i.e., FAS), and for category fluency (i.e., Animal Naming), and with a 32-channel EEG system for ‘eyes-open’ resting theta power. The effects of age, sex, and education were examined using analyses of variance. Correlation analyses were used to test the impact of theta power on age and fluency performance by controlling for the effects of theta when examining the relationship between the other two variables. The results indicated that performance on both fluency tests declined linearly with age, but that the rate of decline was greater for category fluency. These age changes were not associated with education level, and there were no sex differences. While theta power was negatively associated with age and positively associated with Animal Naming performance, it did not moderate the relationship between the two. The differential age-associated decline between category and letter fluency suggests separate neurobiological substrates underlying the two domains of performance, which is not related to theta activity.
PMCID: PMC2758771  PMID: 15939182
Normal aging; Category fluency; Letter fluency; EEG; Theta
5.  The Use of Profanity During Letter Fluency Tasks in Frontotemporal Dementia and Alzheimer's Disease 
To assess whether the production of profanity during letter fluency testing distinguishes frontotemporal dementia (FTD) and Alzheimer's disease (AD) patients.
Alterations in language and social behavior typify FTD spectrum disorders. Nonetheless, in can be difficult to distinguish pathologically-defined frontotemporal lobar degeneration (FTLD) from AD clinically. Assessing verbal fluency by having patients generate as many words as they can beginning with specific letters in a given period of time can yield diverse information of diagnostic utility.
Words produced during FAS letter fluency testing were reviewed and instances of the use of "f*ck", "*ss", and "sh*t" and other words felt to be inappropriate were sought. The frequency of these words was compared between clinically diagnosed FTD and AD patients using chi-square tests.
We found that 6/32 (18.8%) patients with FTD generated the word "f*ck" during the "F" trial as opposed to none of 38 patients with AD (p = 0.007). Patients who said "f*ck" had diagnoses of either behavioral variant FTD (3/15), progressive non-fluent aphasia (2/8), or semantic dementia (1/3).
Though the specific neuropathology in these cases is uncertain, generation of "f*ck" during letter fluency testing appears to have utility in differentiating FTD from AD.
PMCID: PMC3594691  PMID: 20829665
Profanity; Alzheimer's disease; frontotemporal dementia; letter fluency; expletives
6.  The Diagnostic Value of Controlled Oral Word Association Test-FAS and Category Fluency in Single-Domain Amnestic Mild Cognitive Impairment 
Recent studies have shown that decreases in both letter fluency and category fluency may be present in addition to memory impairment in single-domain amnestic mild cognitive impairment (aMCI). However, the clinical utility of these fluency measures is unclear. The aim of this study was to determine what, if any, diagnostic value letter and category fluency provide in differentiating single-domain aMCI from normal cognition.
Data from 66 individuals [33 cognitively normal (CN) and 33 aMCI] between the ages of 66 and 87 years participating in the Florida Alzheimer's Disease Research Center were compared on the Controlled Oral Word Association Test (COWAT)-FAS and Category Fluency test, both in terms of raw and scaled scores.
Participants were matched on age, education and sex. Two-tailed independent sample t-tests found statistically significant differences between the CN and aMCI groups for both raw and scaled scores of COWAT-FAS and Category Fluency (p < 0.001). Logistic regression analyses found that COWAT-FAS and Category Fluency did not significantly improve diagnostic accuracy when combined with the Hopkins Verbal Learning Test-Revised delayed recall.
Although decreased COWAT-FAS and Category Fluency performance may be present in single-domain aMCI, these tests do not improve the ability of the Hopkins Verbal Learning Test-Revised delayed recall to differentiate aMCI from CN individuals.
PMCID: PMC3250647  PMID: 22156335
Prodromal Alzheimer's disease; Alzheimer's disease; Dementia; Neuropsychology; Mild cognitive impairment; Verbal fluency
7.  The differing roles of the frontal cortex in fluency tests 
Brain  2012;135(7):2202-2214.
Fluency tasks have been widely used to tap the voluntary generation of responses. The anatomical correlates of fluency tasks and their sensitivity and specificity have been hotly debated. However, investigation of the cognitive processes involved in voluntary generation of responses and whether generation is supported by a common, general process (e.g. fluid intelligence) or specific cognitive processes underpinned by particular frontal regions has rarely been addressed. This study investigates a range of verbal and non-verbal fluency tasks in patients with unselected focal frontal (n = 47) and posterior (n = 20) lesions. Patients and controls (n = 35) matched for education, age and sex were administered fluency tasks including word (phonemic/semantic), design, gesture and ideational fluency as well as background cognitive tests. Lesions were analysed by standard anterior/posterior and left/right frontal subdivisions as well as a finer-grained frontal localization method. Thus, patients with right and left lateral lesions were compared to patients with superior medial lesions. The results show that all eight fluency tasks are sensitive to frontal lobe damage although only the phonemic word and design fluency tasks were specific to the frontal region. Superior medial patients were the only group to be impaired on all eight fluency tasks, relative to controls, consistent with an energization deficit. The most marked fluency deficits for lateral patients were along material specific lines (i.e. left—phonemic and right—design). Phonemic word fluency that requires greater selection was most severely impaired following left inferior frontal damage. Overall, our results support the notion that frontal functions comprise a set of specialized cognitive processes, supported by distinct frontal regions.
PMCID: PMC3381725  PMID: 22669082
fluency tests; selection; fluid intelligence; energization; frontal cortex
8.  Neural systems supporting lexical search guided by letter and semantic category cues: A self-paced overt response fMRI study of verbal fluency 
NeuroImage  2009;49(1):1099-1107.
Verbal fluency tasks have been widely used to evaluate language and executive control processes in the human brain. FMRI studies of verbal fluency, however, have used either silent word generation (which provides no behavioral measure) or cued generation of single words in order to contend with speech-related motion artifacts. In this study, we use a recently developed paradigm design to investigate the neural correlates of verbal fluency during overt, free recall, word generation so that performance and brain activity could be evaluated under conditions that more closely mirror standard behavioral test demands. We investigated verbal fluency to both letter and category cues in order to evaluate differential involvement of specific frontal and temporal lobe sites as a function of retrieval cue type, as suggested by previous neuropsychological and neuroimaging investigations. In addition, we incorporated both a task switching manipulation and an automatic speech condition in order to modulate the demand placed on executive functions. We found greater activation in the left hemisphere during category and letter fluency tasks, and greater right hemisphere activation during automatic speech. We also found that letter and category fluency tasks were associated with differential involvement of specific regions of the frontal and temporal lobes. These findings provide converging evidence that letter and category fluency performance is dependent on partially distinct neural circuitry. They also provide strong evidence that verbal fluency can be successfully evaluated in the MR environment using overt, self-paced, responses.
PMCID: PMC2832834  PMID: 19632335
9.  Verbal Fluency Performance in Patients with Non-demented Parkinson's Disease 
Iranian Journal of Psychiatry  2013;8(1):55-58.
While Parkinson's disease (PD) has traditionally been defined by motor symptoms, many researches have indicated that mild cognitive impairment is common in non-demented PD patients. The purpose of this study was to compare verbal fluency performance in non-demented Parkinson's disease patients with healthy controls.
In this cross-sectional study thirty non-demented Parkinson's disease patients and 30 healthy controls, matched by age, gender and education, were compared on verbal fluency performance. Verbal fluency was studied with a Phonemic Fluency task using the letters F, A, and S, a semantic fluency task using the categories animals and fruits. The independent t-test was used for data analysis.
Overall, participants generated more words in the semantic fluency task than in the phonemic fluency task. Results revealed significant differences between patients and controls in semantic fluency task (p<.05). In addition, PD patients showed a significant reduction of correctly generated words in letter fluency task. The total number of words produced was also significantly lower in the PD group (p<.05).
Verbal fluency disruption is implied in non-demented PD patients in association with incipient cognitive impairment.
PMCID: PMC3655231  PMID: 23682253
Verbal Fluency; Semantic fluency; Phonemic Fluency; Parkinson's diseas
10.  Phonological Fluency Strategy of Switching Differentiates Relapsing-Remitting and Secondary Progressive Multiple Sclerosis Patients 
ISRN Neurology  2013;2013:451429.
The strategies used to perform a verbal fluency task appear to be reflective of cognitive abilities necessary for successful daily functioning. In the present study, we explored potential differences in verbal fluency strategies (switching and clustering) used to maximize word production by patients with relapsing-remitting multiple sclerosis (RRMS) versus patients with secondary progressive multiple sclerosis (SPMS). We further assessed impairment rates and potential differences in the sensitivity and specificity of phonological versus semantic verbal fluency tasks in discriminating between those with a diagnosis of MS and healthy adults. We found that the overall rate of impaired verbal fluency in our MS sample was consistent with that in other studies. However, we found no differences between types of MS (SPMS, RRMS), on semantic or phonological fluency word production, or the strategies used to maximize semantic fluency. In contrast, we found that the number of switches differed significantly in the phonological fluency task between the SPMS and RRMS subtypes. The clinical utility of semantic versus phonological fluency in discriminating MS patients from healthy controls did not indicate any significant differences. Further, the strategies used to maximize performance did not differentiate MS subgroups or MS patients from healthy controls.
PMCID: PMC3562673  PMID: 23401793
11.  The Frontal-Anatomic Specificity of Design Fluency Repetitions and their Diagnostic Relevance for Behavioral Variant Frontotemporal Dementia 
On tests of design fluency, an examinee draws as many different designs as possible in a specified time limit while avoiding repetition. The neuroanatomical substrates and diagnostic group differences of design fluency repetition errors and total correct scores were examined in 110 individuals diagnosed with dementia, 53 with mild cognitive impairment (MCI), and 37 neurologically healthy controls. The errors correlated significantly with volumes in the right and left orbitofrontal cortex (OFC), the right and left superior frontal gyrus, the right inferior frontal gyrus, and the right striatum, but did not correlate with volumes in any parietal or temporal lobe regions. Regression analyses indicated that the lateral OFC may be particularly crucial for preventing these errors, even after excluding patients with behavioral variant frontotemporal dementia (bvFTD) from the analysis. Total correct correlated more diffusely with volumes in the right and left frontal and parietal cortex, the right temporal cortex, and the right striatum and thalamus. Patients diagnosed with bvFTD made significantly more repetition errors than patients diagnosed with MCI, Alzheimer’s disease, semantic dementia, progressive supranuclear palsy or corticobasal syndrome. In contrast, total correct design scores did not differentiate the dementia patients. These results highlight the frontal-anatomic specificity of design fluency repetitions. In addition, the results indicate that the propensity to make these errors supports the diagnosis of bvFTD.
PMCID: PMC3620020  PMID: 22835330
Perseveration; Orbitofrontal; Neuropsychology; Executive Function; Dementia; Process Approach
12.  Automated Semantic Indices Related to Cognitive Function and Rate of Cognitive Decline 
Neuropsychologia  2012;50(9):2165-2175.
The objective of our study is to introduce a fully automated, computational linguistic technique to quantify semantic relations between words generated on a standard semantic verbal fluency test and to determine its cognitive and clinical correlates. Cognitive differences between patients with Alzheimer’s disease and mild cognitive impairment are evident in their performance on the semantic verbal fluency test. In addition to the semantic verbal fluency test score, several other performance characteristics sensitive to disease status and predictive of future cognitive decline have been defined in terms of words generated from semantically related categories (clustering) and shifting between categories (switching). However, the traditional assessment of clustering and switching has been performed manually in a qualitative fashion resulting in subjective scoring with limited reproducibility and scalability. Our approach uses word definitions and hierarchical relations between the words in WordNet®, a large electronic lexical database, to quantify the degree of semantic similarity and relatedness between words. We investigated the novel semantic fluency indices of mean cumulative similarity and relatedness between all pairs of words regardless of their order, and mean sequential similarity and relatedness between pairs of adjacent words in a sample of patients with clinically diagnosed probable (n=55) or possible (n=27) Alzheimer’s disease or mild cognitive impairment (n=31). The semantic fluency indices differed significantly between the diagnostic groups, and were strongly associated with neuropsychological tests of executive function, as well as the rate of global cognitive decline. Our results suggest that word meanings and relations between words shared across individuals and computationally modeled via WordNet and large text corpora provide the necessary context to account for the variability in language-based behavior and relate it to cognitive dysfunction observed in mild cognitive impairment and Alzheimer’s disease.
PMCID: PMC3404821  PMID: 22659109
semantic verbal fluency; Alzheimer’s disease; mild cognitive impairment; semantic similarity; semantic relatedness; computational semantics
13.  Drug Fluency: A Potential Marker for Cocaine Use Disorders 
Drug and alcohol dependence  2007;89(1):97-101.
The goal of the current study was to tailor semantic fluency to increase its sensitivity and ecological validity in the study of drug use disorders. On a newly modified “drug” fluency task, individuals with cocaine use disorders who tested positive for cocaine at study day named more drug-related words than control subjects. The number of words provided on the classical semantic fluency task (animals and fruits/vegetables) did not differ between the groups. While the individuals with cocaine use disorders who tested negative for cocaine at study day did not differ from the control subjects in total words named on this task, a qualitative analysis indicated that both cocaine subgroups provided significantly more words pertaining to the experience of using drugs (paraphernalia, administration) than the matched control subjects. These results demonstrate that compared to classical neurocognitive assessment tools, newly tailored measures may be more sensitive to cocaine use disorders, psychopathologies that are often characterized by mild neuropsychological deficits but a well-circumscribed attentional bias to drug-related cues. Future studies are needed to probe the exact cognitive processes and neural circuitry underlying performance on this cue-sensitive 1-minute measure.
PMCID: PMC1892225  PMID: 17234364
semantic memory; cocaine; drug addiction; salience; cue-reactivity; craving; prefrontal cortex
14.  Differential Impacts of Age of Acquisition on Letter and Semantic Fluency in Alzheimer’s Disease Patients and Healthy Older Adults 
The degree to which the typical age of acquisition (AoA) of words and word frequency have separable influences on verbal production tasks has been strongly debated. To examine the overlap between these factors in verbal fluency tasks, the performance of Alzheimer’s disease (AD) patients (N=34) and normal elderly controls (N=36) was compared on semantic (e.g., vegetables) and letter (e.g. words that begin with F) fluency tasks. These comparisons revealed that words generated for the semantic fluency task had an earlier AoA while words generated for the letter fluency task had a higher word frequency.. Differences in AoA between AD patients and controls were larger for semantic than letter fluency. These results suggest that AoA has an effect on verbal production that is independent of word frequency and that AoA has a semantic locus.
PMCID: PMC3671596  PMID: 21851152
15.  Specific Measures of Executive Function Predict Cognitive Decline in Older Adults 
Decline in executive function has been noted in the prodromal stage of Alzheimer’s disease (AD) and may presage more global cognitive declines. In this prospective longitudinal study, five measures of executive function were used to predict subsequent global cognitive decline in initially nondemented older adults. Of 71 participants, 15 demonstrated significant decline over a 1-year period on the Dementia Rating Scale (Mattis, 1988) and the remaining participants remained stable. In the year before decline, the decline group performed significantly worse than the no-decline group on two measures of executive function: the Color-Word Interference Test (CWIT; inhibition/switching condition) and Verbal Fluency (VF; switching condition). In contrast, decliners and non-decliners performed similarly on measures of spatial fluency (Design Fluency switching condition), spatial planning (Tower Test), and number-letter switching (Trail Making Test switching condition). Furthermore, the CWIT inhibition-switching measure significantly improved the prediction of decline and no-decline group classification beyond that of learning and memory measures. These findings suggest that some executive function measures requiring inhibition and switching provide predictive utility of subsequent global cognitive decline independent of episodic memory and may further facilitate early detection of dementia.
PMCID: PMC3314335  PMID: 22115028
Executive functions; Global cognition; Switching; Prodromal Alzheimer’s disease; Mild cognitive impairment; Prediction
16.  Language in Alzheimer's Disease 
The Journal of clinical psychiatry  2008;69(8):1223-1227.
To ascertain the clinical utility of language examination by psychiatrists in evaluating Alzheimer's disease (AD) patients.
Data collected between 1986 and 2003 from a standardized psychiatric examination and neuropsychological testing of probable AD patients (diagnosed according to the criteria of the National Institute of Neurological and Communicative Disorders and Stroke and the Alzheimer's Disease and Related Disorders Association) were gathered from the database of the University of Texas Southwestern Alzheimer's Disease Center, Dallas. The variables studied were articulation, word-finding ability, hypofluency, hyperfluency, repetition, confrontational naming, and semantic (category) fluency Articulation, word-finding ability, hypofluency, hyperfluency, repetition, and confrontational naming were rated as normal or abnormal. Semantic fluency was scored numerically as the number of animals named in a minute. Cognitive impairment was assessed with the Mini-Mental State Examination (MMSE) and global impairment by the Clinical Dementia Rating (CDR) scale.
There was a significant association (p < .0001) between MMSE and CDR scores for all language measures except hyperfluency. The MMSE scores were higher in the group with responses rated as normal compared to those with abnormal responses. Patients with greater cognitive and global impairment named fewer animals in a minute.
Abnormal articulation and repetition of words were unusual and therefore would not be useful for early detection, but when present, were associated with more advanced disease. Impairment in fluency, animal naming, and confrontational naming were common and increased in frequency with greater cognitive and global impairment. Because animal naming is a numerical measure, changes in the number of animals named in a minute can be used to monitor disease progression.
PMCID: PMC3177322  PMID: 18505305
17.  Systematic instruction for individuals with acquired brain injury: Results of a randomized controlled trial 
The goal of this study was to experimentally evaluate systematic instruction compared with trial-and-error learning (conventional instruction) applied to assistive technology for cognition (ATC), in a double blind, pretest-posttest, randomized controlled trial. Twenty-nine persons with moderate-severe cognitive impairments due to acquired brain injury (15 in systematic instruction group; 14 in conventional instruction) completed the study. Both groups received 12, 45-minute individual training sessions targeting selected skills on the Palm Tungsten E2 personal digital assistant (PDA). A criterion-based assessment of PDA skills was used to evaluate accuracy, fluency/efficiency, maintenance, and generalization of skills. There were no significant differences between groups at immediate posttest with regard to accuracy and fluency. However, significant differences emerged at 30-day follow-up in favor of systematic instruction. Furthermore, systematic instruction participants performed significantly better at immediate posttest generalizing trained PDA skills when interacting with people other than the instructor. These results demonstrate that systematic instruction applied to ATC results in better skill maintenance and generalization than trial-and-error learning for individuals with moderate-severe cognitive impairments due to acquired brain injury. Implications, study limitations, and directions for future research are discussed.
PMCID: PMC3279115  PMID: 22264146
instruction; errorless learning; assistive technology; memory; cognitive impairment
18.  Frontal lobe abnormalities on MRS correlate with poor letter fluency in ALS 
Neurology  2012;79(6):583-588.
To examine whether frontal lobe abnormalities on magnetic resonance spectroscopy (MRS) in amyotrophic lateral sclerosis (ALS) correlate with poor letter fluency (LF).
Twenty-five patients with ALS (20 with definite, probable, or possible ALS and 5 with progressive muscular atrophy) performed an LF task, involving F word generation in 1 minute, and underwent MRS. Comparisons were made between patients with ALS with impaired LF and unimpaired LF based on an empirically derived cutoff score. A Spearman correlation was performed between the patient's N-acetyl acetate/creatinine-phosphocreatinine ratio (NAA/Cr) and the number of F words generated.
LF was impaired in 50% of patients with ALS. Patients with impaired LF had reduced NAA/Cr in the DLPFC compared with those with unimpaired LF (p = 0.007). There was a significant correlation between LF and NAA/Cr in the DLPFC (r = 0.51, p = 0.0009). The ALS Functional Rating Scale score, clinical region of motor onset, and disease category had no effect on LF or NAA/Cr in the DLPFC.
A reduced NAA/Cr in the DLPFC of patients with ALS is a marker of neuronal dysfunction and correlates with impaired performance on a clinical measure of executive function.
PMCID: PMC3413764  PMID: 22843269
19.  Dysexecutive Functioning in Mild Cognitive Impairment: Derailment in Temporal Gradients 
Libon et al. (2010) provided evidence for three statistically determined clusters of patients with mild cognitive impairment (MCI): amnesic (aMCI), dysexecutive (dMCI), and mixed (mxMCI). The current study further examined dysexecutive impairment in MCI using the framework of Fuster's (1997) derailed temporal gradients, that is, declining performance on executive tests over time or test epoch. Temporal gradients were operationally defined by calculating the slope of aggregate letter fluency output across 15-s epochs and accuracy indices for initial, middle, and latter triads from the Wechsler Memory Scale-Mental Control subtest (Boston Revision). For letter fluency, slope was steeper for dMCI compared to aMCI and NC groups. Between-group Mental Control analyses for triad 1 revealed worse dMCI performance than NC participants. On triad 2, dMCI scored lower than aMCI and NCs; on triad 3, mxMCI performed worse versus NCs. Within-group Mental Control analyses yielded equal performance across all triads for aMCI and NC participants. mxMCI scored lower on triad 1 compared to triads 2 and 3. dMCI participants also performed worse on triad 1 compared to triads 2 and 3, but scored higher on triad 3 versus triad 2. These data suggest impaired temporal gradients may provide a useful heuristic for understanding dysexecutive impairment in MCI.
PMCID: PMC3315354  PMID: 22014116
Mild cognitive impairment; Single domain mild cognitive impairment; Multiple domain mild cognitive impairment; Alzheimer's disease; The Titanic Effect; Executive control
20.  Longitudinal verbal fluency in normal aging, preclinical and prevalent Alzheimer disease 
Few longitudinal studies evaluate differences in patterns of change of category compared to letter fluency across the spectrum of cognitive impairment.
We compared change in category (animal and supermarket) and letter (F,A,S) fluency among 239 participants in three groups: remained cognitively normal throughout follow-up (n=96), developed AD (preclinical AD, n=21), and with AD at initial testing (prevalent AD, n=122).
At baseline, prevalent and preclinical AD groups scored lower on animal than letter fluency. On all fluency measures, the prevalent AD declined faster than other groups (all p<0.0001), and preclinical AD declined faster than unimpaired (all p≤0.02). Overall, animal fluency declined faster than letter fluency; animal fluency declined significantly faster than letter fluency among cognitively normal and prevalent AD subjects.
Greater longitudinal declines in category compared to letter fluency are consistent with cross-sectional studies. Steeper declines on both fluency measures distinguish preclinical AD from cognitively unimpaired individuals.
PMCID: PMC2824246  PMID: 19759254
dementia; neuropsychology; fluency; Alzheimer disease; semantic memory; cognitive impairment
21.  Why are patients with progressive nonfluent aphasia nonfluent? 
Neurology  2010;75(7):588-594.
To investigate the cognitive and neural basis for nonfluent speech in progressive nonfluent aphasia (PNFA).
Nonfluent speech is the hallmark feature of PNFA, and this has been attributed to impairments in syntactic processing, motor-speech planning, and executive functioning that also occur in these patients. Patients with PNFA have left inferior frontal atrophy.
A large semi-structured speech sample and neuropsychological measures of language and executive functioning were examined in 16 patients with PNFA, 12 patients with behavioral-variant frontotemporal dementia (bvFTD), and 13 age-matched controls. Speech fluency was quantified as words per minute (WPM) in the semi-structured speech sample. Stepwise linear regression analyses were used to relate WPM to grammatic, motor-speech planning, and executive aspects of patient functioning. These measures were then related to cortical thickness in 8 patients with PNFA and 7 patients with bvFTD using structural MRI.
WPM was significantly reduced in patients with PNFA relative to controls and patients with bvFTD. Regression analyses revealed that only grammatic measures predicted WPM in PNFA, whereas executive measures were the only significant predictor of WPM in bvFTD. Cortical thinning was significant in PNFA relative to controls in left inferior frontal and anterior-superior temporal regions, and a regression analysis related this area to reduced WPM in PNFA. Significant cortical thinning associated with limited grammatic processing also was seen in the left inferior frontal-superior temporal region in PNFA, and this overlapped with the area of frontal-temporal thinning related to reduced WPM.
Nonfluent speech in PNFA may be due in part to difficulty with grammatic processing associated with left inferior frontal and anterior-superior temporal disease.
= apraxia of speech;
= anterior superior temporal cortex;
= behavioral-variant frontotemporal dementia;
= corticobasal degeneration;
= corticobasal syndrome;
= frontotemporal lobar degeneration;
= inferior frontal cortex;
= progressive nonfluent aphasia;
= progressive supranuclear palsy;
= words per minute.
PMCID: PMC2931767  PMID: 20713947
22.  Phonological grouping is specifically affected in cerebellar patients: a verbal fluency study 
OBJECTIVES—Recent clinical and functional neuroimaging evidence points towards a cerebellar role in verbal production. At present it is not clear how the cerebellum participates in language production. The aim was to investigate the influence of cerebellar lesions on verbal fluency abilities with specific focus on the verbal searching strategies employed by patients with cerebellar damage.
METHODS—Twenty five patients with focal or degenerative cerebellar disease and 14 control subjects were tested in a timed verbal fluency task requiring word production under forced (phonemic or semantic) conditions. To analyse the verbal searching strategy employed, semantic and phonemic cluster analyses were also performed.
RESULTS—Performances of cerebellar patients were comparable with those of controls in the semantic task; conversely their performances were significantly impaired when tested in the letter task. Cluster analysis results showed that the verbal fluency impairment is linked to specific damage of phonemically related retrieval strategies.
CONCLUSION—Cerebellar damage impairs verbal fluency by specifically affecting phonemic rule performances while sparing semantic rule ones. These findings underline the importance of the cerebellar computing properties in strategy development in the linguistic domain.

PMCID: PMC1736989  PMID: 10864613
23.  Which part of the Quick mild cognitive impairment screen (Qmci) discriminates between normal cognition, mild cognitive impairment and dementia? 
Age and Ageing  2013;42(3):324-330.
Introduction: the Qmci is a sensitive and specific test to differentiate between normal cognition (NC), mild cognitive impairment (MCI) and dementia. We compared the sensitivity and specificity of the subtests of the Qmci to determine which best discriminated NC, MCI and dementia.
Objective: the objective was to determine the contribution each subtest of the Qmci makes, to its sensitivity and specificity in differentiating MCI from NC and dementia, to refine and shorten the instrument.
Methods: existing data from our previous study of 965 subjects, testing the Qmci, was analysed to compare the sensitivity and specificity of the Qmci subtests.
Results: all the subtests of the Qmci differentiated MCI from NC. Logical memory (LM) performed the best (area under the receiver operating curve of 0.80), registration the worst, (0.56). LM and verbal fluency had the largest median differences (expressed as percentage of total score) between MCI and NC, 20 and 25%, respectively. Other subtests did not have clinically useful differences. LM was best at differentiating MCI from NC, irrespective of age or educational status.
Conclusion: the Qmci incorporates several important cognitive domains making it useful across the spectrum of cognitive impairment. LM is the best performing subtest for differentiating MCI from NC.
PMCID: PMC3633367  PMID: 23612864
Quick mild cognitive impairment screen; mild cognitive impairment; standardised Mini-Mental State Examination; sensitivity and specificity; cognitive domains
24.  A Score Based on Screening Tests to Differentiate Mild Cognitive Impairment from Subjective Memory Complaints 
Neurology International  2013;5(3):e16.
It is not easy to differentiate patients with mild cognitive impairment (MCI) from subjective memory complainers (SMC). Assessments with screening cognitive tools are essential, particularly in primary care where most patients are seen. The objective of this study was to evaluate the diagnostic accuracy of screening cognitive tests and to propose a score derived from screening tests. Elderly subjects with memory complaints were evaluated using the Mini Mental State Examination (MMSE) and the Brief Cognitive Battery (BCB). We added two delayed recalls in the MMSE (a delayed recall and a late-delayed recall, LDR), and also a phonemic fluency test of letter P fluency (LPF). A score was created based on these tests. The diagnoses were made on the basis of clinical consensus and neuropsychological testing. Receiver operating characteristic curve analyses were used to determine area under the curve (AUC), the sensitivity and specificity for each test separately and for the final proposed score. MMSE, LDR, LPF and delayed recall of BCB scores reach statistically significant differences between groups (P=0.000, 0.03, 0.001 and 0.01, respectively). Sensitivity, specificity and AUC were MMSE: 64%, 79% and 0.75 (cut off <29); LDR: 56%, 62% and 0.62 (cut off <3); LPF: 71%, 71% and 0.71 (cut off <14); delayed recall of BCB: 56%, 82% and 0.68 (cut off <9). The proposed score reached a sensitivity of 88% and 76% and specificity of 62% and 75% for cut off over 1 and over 2, respectively. AUC were 0.81. In conclusion, a score created from screening tests is capable of discriminating MCI from SMC with moderate to good accurancy.
PMCID: PMC3794451  PMID: 24147213
mild cognitive impairment; subjective memory complaints; screening cognitive test; diagnostic score
25.  Age and Verbal Fluency: The Mediating Effect of Speed of Processing 
Background and Purpose
Cognitive decline is a function of normal aging; however, the effect of age on various domains is differential. This study examined the effect of age on verbal fluency and showed how speed of processing modifies fluency performance in healthy older adults compared to younger individuals.
Three age groups, 62 young (17–40 years), 30 middle-aged (41–59 years), and 38 older adults (60–78 years), were studied using the Controlled Oral Word Association Test, National Adult Reading Test, and speed-of-processing composite score. The study examined the effect of age on fluency before and after controlling for processing speed and intelligence quotient.
The young group performed better than the older group on category fluency as measured by animal category (p < .001) and on processing speed composite score (p < .001). However, the older group performed better than the young group on the National Adult Reading Test (p < .05) and on letter fluency after controlling for the decline in processing speed (p < .05). Processing speed had a significant effect on both category and letter fluency (p < .01) in older adults.
This study suggests that aging adversely affects some but not all cognitive domains and that age-related decline in processing speed contributes to age-related changes in fluency.
PMCID: PMC3516352  PMID: 23251316
aging; cognitive function; premorbid IQ; verbal fluency; speed of processing; verbal knowledge

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