The effect of topiramate plasma concentration on linguistic behavior, verbal recall and working memory

Marino, Susan E.; Pakhomov, Serguei; Han, Sahng min; Anderson, Kathleen; Ding, Mingzhou; Eberly, Lynn E.; Loring, David W.; Hawkins‐Taylor, Chamika; Rarick, John O.; Leppik, Ilo E.; Cibula, Jean E.; Birnbaum, Angela K.

doi:10.1016/j.yebeh.2012.04.120

Cited by 28 publications

(27 citation statements)

References 45 publications

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“…The semantic test (SVF) consists of naming words belonging to a semantic category (e.g., animals). These tests have been demonstrated to be useful for characterization of cognitive impairment due to a number of conditions including neurodegenerative disease (Henry et al, 2005, 2004; Henry and Crawford, 2004a), psychiatric diagnoses (Henry and Crawford, 2005), developmental disorders (Spek et al, 2009), drug toxicity or metabolic effects (Marino et al, 2012; Witt et al, 2013), as well as impairment due to traumatic brain injury or cardiovascular accidents (Henry and Crawford, 2004b, 2004c). In particular, contact sports such as boxing, mixed martial arts, football, and hockey are particularly well-known for high prevalence of repetitive head trauma which is a major risk factor for chronic traumatic encephalopathy (CTE), a devastating and untreatable condition that ultimately results in permanent disability and premature death (McKee et al, 2013).…”

Section: Introductionmentioning

confidence: 99%

Using automatic speech recognition to assess spoken responses to cognitive tests of semantic verbal fluency

Pakhomov

Marino

Banks

et al. 2015

Speech Communication

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Cognitive tests of verbal fluency (VF) consist of verbalizing as many words as possible in one minute that either start with a specific letter of the alphabet or belong to a specific semantic category. These tests are widely used in neurological, psychiatric, mental health, and school settings and their validity for clinical applications has been extensively demonstrated. However, VF tests are currently administered and scored manually making them too cumbersome to use, particularly for longitudinal cognitive monitoring in large populations. The objective of the current study was to determine if automatic speech recognition (ASR) could be used for computerized administration and scoring of VF tests. We examined established techniques for constraining language modeling to a predefined vocabulary from a specific semantic category (e.g., animals). We also experimented with post-processing ASR output with confidence scoring, as well as with using speaker adaptation to improve automated VF scoring. Audio responses to a VF task were collected from 38 novice and experienced professional fighters (boxing and mixed martial arts) participating in a longitudinal study of effects of repetitive head trauma on brain function. Word error rate, correlation with manual word count and distance from manual word count were used to compare ASR-based approaches to scoring to each other and to the manually scored reference standard. Our study's results show that responses to the VF task contain a large number of extraneous utterances and noise that lead to relatively poor baseline ASR performance. However, we also found that speaker adaptation combined with confidence scoring significantly improves all three metrics and can enable use of ASR for reliable estimates of the traditional manual VF scores.

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Section: Introductionmentioning

confidence: 99%

Using automatic speech recognition to assess spoken responses to cognitive tests of semantic verbal fluency

Pakhomov

Marino

Banks

et al. 2015

Speech Communication

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“…Topiramate (TPM), 2,3:4,5‐bis‐ O ‐(1‐methylethylidene)‐β‐ d ‐fructopyranose sulfamate, with indications as monotherapy for recently diagnosed partial epilepsy, add‐on treatment for resistant partial‐onset seizures and prophylactic treatment for migraine, is also being prescribed for a range of other conditions, including obesity, pain, bipolar disorder and alcoholism . Topiramate has been widely reported to cause adverse cognitive effects specifically related to working memory and verbal fluency in healthy volunteers and patients with epilepsy and migraine .…”

Section: Introductionmentioning

confidence: 99%

Pharmacokinetic–pharmacodynamic modelling of intravenous and oral topiramate and its effect on phonemic fluency in adult healthy volunteers

Ahmed

Marino

Brundage

et al. 2015

Brit J Clinical Pharma

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AIMSThe aim was to develop a quantitative approach that characterizes the magnitude of and variability in phonemic generative fluency scores as measured by the Controlled Oral Word Association (COWA) test in healthy volunteers after administration of an oral and a novel intravenous (IV) formulation of topiramate (TPM). METHODSNonlinear mixed-effects modelling was used to describe the plasma TPM concentrations resulting from oral or IV administration. A pharmacokineticpharmacodynamic (PK-PD) model was developed sequentially to characterize the effect of TPM concentrations on COWA with different distributional assumptions. RESULTSTopiramate was rapidly absorbed, with a median time to maximal concentration of 1 h and an oral bioavailability of ∼100%. Baseline COWA score increased by an average of 12% after the third administration on drug-free sessions. An exponential model described the decline of COWA scores, which decreased by 14.5% for each 1 mg l −1 increase in TPM concentration. The COWA scores were described equally well by both continuous normal and Poisson distributions. CONCLUSIONSThis analysis quantified the effect of TPM exposure on generative verbal fluency as measured by COWA. Repetitive administration of COWA resulted in a better performance, possibly due to a learning effect. The model predicts a 27% reduction in the COWA score at the average observed maximal plasma concentration after a 100 mg dose of TPM. The single-dose administration of relatively low TPM doses and narrow range of resultant concentrations in our study were limitations to investigating the PK-PD relationship at higher TPM exposures. Hence, the findings may not be readily generalized to the broader patient population. WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT• Topiramate has a selective and persistent effect on generative fluency, with a highly variable incidence (3-44%) across studies.• Several factors may contribute to the interindividual variability in cognitive effects of topiramate, including dose and rapid titration.• The relationship of cognitive impairment to drug concentration has not been thoroughly evaluated. WHAT THIS STUDY ADDS• This study presents an exposure-response model that quantifies the effect of topiramate concentration on phonemic fluency. • We found that the Controlled Oral Word Association scores increase upon repeated administration and decline with increased topiramate exposure.• This model provides a foundation for future testing of factors that predict topiramate-induced cognitive impairment.

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“…We decided to use a single letter “F” in order to minimize the amount of testing time and based on reports in the literature that results obtained with letter “F” tend to be similar to those obtained with 3-letter combinations (Ruff et al, 1996; Tombaugh, Kozak, & Rees, 1999) and thus is frequently used in clinical settings as a bedside test (Lezak et al, 2004). While this pilot study was not designed to assess concurrent and predictive validity of SVF and PVF testing, these tests have been well established and widely used for assessment of cognitive function in populations affected by neurodegenerative disease, traumatic brain injury, developmental disorders, and drug toxicity (Burgess et al, 1998; Doesborgh et al, 2002; Henry & Crawford, 2004a, 2004b, 2004c, 2005; Henry et al, 2004, 2005; Marino et al, 2012; Spek et al, 2009; Witt et al, 2013). Future studies are needed to assess the concurrent and predictive validity of VF testing in the context of cognitive effects of smoking and nicotine withdrawal.…”

Section: Discussionmentioning

confidence: 99%

“…Word retrieval on both PVF and SVF tests relies on both frontal and temporal cognitive mechanisms; however, PVF relies more heavily on frontal function (working memory, inhibition of inappropriate responses and sustained attention) than SVF, and SVF relies more heavily on temporal function (semantic memory) than PVF. PVF and SVF tests have been widely used in neurological, psychiatric, mental health, and school settings and their construct and ecological validity have been extensively demonstrated (Burgess et al, 1998; Doesborgh et al, 2002; Henry & Crawford, 2004a, 2004b, 2004c, 2005; Henry, Crawford, & Phillips, 2004, 2005; Marino et al, 2012; Spek, Schatorje, Scholte, & van Berckelaer-Onnes, 2009; Witt, Elger, & Helmstaedter, 2013). …”

Section: Introductionmentioning

confidence: 99%

Use of an automated mobile application to assess effects of nicotine withdrawal on verbal fluency: A pilot study.

Pakhomov¹,

Teeple²,

Mills³

et al. 2016

Experimental and Clinical Psychopharmacology

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Mild-to-moderate impairment in frontally mediated functions such as sustained attention, working memory and inhibition have been found to occur during tobacco withdrawal and may present a barrier to successful cessation. These findings have led to studies evaluating cessation treatments that target nicotine withdrawal related cognitive impairment. The instruments currently used to assess cognitive function provide detailed and specific information but have limitations including being time consuming, cumbersome, anxiety provoking and having poor ecological validity. We examined the feasibility of using a mobile computer application to test verbal fluency (VF) as a quick, easy-to-administer and more ecologically valid method of measuring the effects of short-term smoking abstinence on frontally mediated cognitive functions. Thirty participants completed two assessments – one during ad lib smoking and one after overnight abstinence. At each assessment, semantic and phonemic VF tests were administered using a mobile application and nicotine craving and withdrawal symptom severity was assessed. In repeated assessments, performance on both semantic and phonemic VF tests is expected to improve due to practice effects; however, significant improvements were observed only in semantic (p=0.012) but not phonemic (p=0.154) VF. Additionally, the change between assessments in phonemic (but not semantic) score was significantly associated with withdrawal (p=0.006) and craving (p=0.037) severity measured post-abstinence. This study demonstrates that nicotine withdrawal has differential effects on semantic versus phonemic VF suggesting impairments of working memory, attention, and inhibition. These effects were measured using methods easily employed in large groups of participants, potentially with remote test administration and automated scoring.

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The effect of topiramate plasma concentration on linguistic behavior, verbal recall and working memory

Cited by 28 publications

References 45 publications

Using automatic speech recognition to assess spoken responses to cognitive tests of semantic verbal fluency

Using automatic speech recognition to assess spoken responses to cognitive tests of semantic verbal fluency

Pharmacokinetic–pharmacodynamic modelling of intravenous and oral topiramate and its effect on phonemic fluency in adult healthy volunteers

Use of an automated mobile application to assess effects of nicotine withdrawal on verbal fluency: A pilot study.

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