No full-text available
To read the full-text of this research,
you can request a copy directly from the authors.
When verbal fluency inverts: Temporality of semantic impairment in preclinical Alzheimer’s disease
Alzheimer's & Dementia
Abstract
Background
Worse semantic than letter fluency performance is a clinical marker of Alzheimer’s disease (AD), but the longitudinal course of performance on these tasks in pre‐dementia stages remains undefined. This study investigated how many years before clinical AD the performance on the two verbal fluency tasks starts to diverge, and if this process develops similarly across race/ethnicity groups.
Method
To estimate the trajectories and inflection point of verbal fluency performance in years prior to AD diagnosis, we performed piece‐wise linear mixed effects models in a diverse sample of 569 individuals (mean age = 78.5) from a community‐based cohort who were cognitively normal at baseline but developed dementia across 10 years of follow‐up (up to 5 visits). Performance was standardized on 569 age, sex/gender, education, and race/ethnicity matched controls who remained cognitively healthy during follow‐up (i.e., robust norms approach). Models were adjusted for recruitment wave and demographic factors.
Result
AIC model comparison of spline‐fit revealed that prior to AD diagnosis, performance on both fluency tasks started to decline more rapidly 3.6 years before diagnosis (slope within later timeframe: semantic: B=‐1.34 [‐1.52, ‐1.16], p<.001; letter: B=‐.56 [‐.70, ‐.42], p<.001). Point‐in‐time performance on semantic fluency became worse than letter fluency as of approximately 2.8 years before AD diagnosis due to the disproportionally fast decline of semantic fluency. Stratified models showed that the inflection point for Whites was earlier than for Blacks and Hispanics, but that the rate of decline and flip in performance between the two tasks was similar across race/ethnicity.
Conclusion
These results show how the conventional clinical index of worse semantic than letter fluency develops over time in the years before AD diagnosis. This study highlights the importance of serial neuropsychological assessments in detecting high‐risk individuals by showing that the differential rate of decline in semantic versus letter fluency is a sensitive preclinical AD‐marker, equivalent across race/ethnicity.
... As a complement to core learning and recall tests, Alzheimer's disease (AD) assessments typically include verbal fluency tasks. 1 Participants have 1 min to produce words that begin with a given sound (phonemic fluency) or belong to a given category (semantic fluency). 2 These tasks, especially in the semantic condition, reveal early and preclinical deficits 3 which predict anatomo-functional brain dysfunctions. 4,5 Moreover, they are brief, inexpensive, and massively available, 6 highlighting their potential to reveal scalable AD markers. ...
... 51 Our results bear clinical implications. Verbal fluency tasks are widely used to assess AD, other neurodegenerative disorders, 1,3,8,10,12,13,16,60 and relevant phenomena, such as cognitive reserve. 70 Yet, standard scoring diminishes their potential for revealing disease-differential markers. ...
INTRODUCTION
Verbal fluency tasks are common in Alzheimer's disease (AD) assessments. Yet, standard valid response counts fail to reveal disease‐specific semantic memory patterns. Here, we leveraged automated word‐property analysis to capture neurocognitive markers of AD vis‐à‐vis behavioral variant frontotemporal dementia (bvFTD).
METHODS
Patients and healthy controls completed two fluency tasks. We counted valid responses and computed each word's frequency, granularity, neighborhood, length, familiarity, and imageability. These features were used for group‐level discrimination, patient‐level identification, and correlations with executive and neural (magnetic resonanance imaging [MRI], functional MRI [fMRI], electroencephalography [EEG]) patterns.
RESULTS
Valid responses revealed deficits in both disorders. Conversely, frequency, granularity, and neighborhood yielded robust group‐ and subject‐level discrimination only in AD, also predicting executive outcomes. Disease‐specific cortical thickness patterns were predicted by frequency in both disorders. Default‐mode and salience network hypoconnectivity, and EEG beta hypoconnectivity, were predicted by frequency and granularity only in AD.
DISCUSSION
Word‐property analysis of fluency can boost AD characterization and diagnosis.
Highlights
We report novel word‐property analyses of verbal fluency in AD and bvFTD.
Standard valid response counts captured deficits and brain patterns in both groups.
Specific word properties (e.g., frequency, granularity) were altered only in AD.
Such properties predicted cognitive and neural (MRI, fMRI, EEG) patterns in AD.
Word‐property analysis of fluency can boost AD characterization and diagnosis.
... Regarding our approach, one issue is that the sequence information and the item-level metrics we used rely on the number of correct words produced by the participant. Although this is common practice (Rofes et al., 2019;Thiele et al., 2016;Troyer et al., 1997;Vonk, Flores, et al., 2019;Vonk et al., 2021), it is unknown whether a minimum number of words may be necessary to provide reliable results for these kinds of analyses. This concern seems relatively minor for studies of cognitively healthy individuals who can produce a normal number of words. ...
Purpose
In this study, we aim to understand whether and how performance in animal fluency (i.e., total correct word count) relates to linguistic levels and/or executive functions by looking at sequence information and item-level metrics (i.e., clusters, switches, and word properties).
Method
Seven hundred thirty-one Dutch-speaking individuals without dementia from the Second Manifestations of ARTerial disease-Magnetic Resonance study responded to an animal fluency task (120 s). We obtained cluster size and number of switches for the task, and eight different word properties for each correct word produced. We detected variables that determine total word count with random forests, and used conditional inference trees to assess points along the scales of such variables, at which total word count changes significantly.
Results
Number of switches, average cluster size, lexical decision response times, word frequency, and concreteness determined total correct word count in animal fluency. People who produced more correct words produced more switches and bigger clusters. People who produced fewer words produced fewer switches and more frequent words.
Conclusions
Concurrent with existing literature, individuals without dementia rely on language and executive functioning to produce words in animal fluency. The novelty of our work is that such results were shown based on a data-driven approach using sequence information and item-level metrics.
Supplemental Material
https://doi.org/10.23641/asha.23713269
ResearchGate has not been able to resolve any references for this publication.