ERP abnormalities elicited by word repetition in fragile X-associated tremor/ataxia syndrome (FXTAS) and amnestic MCI

Yang, Jin; Chi, Lillian; Teichholtz, Sara; Schneider, Andrea; Nanakul, Rawi; Nowacki, Ralph; Seritan, Andreea L.; Reed, Bruce R; DeCarli, Charles; Iragui, Vicente J.; Kutas, Marta; Hagerman, Paul J.; Hagerman, Randi J; Olichney, John

doi:10.1016/j.neuropsychologia.2014.08.001

Cited by 21 publications

(15 citation statements)

References 46 publications

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“…Only one previous controlled trial has been performed in individuals with FXTAS, a memantine trial lasting 1 year, but this treatment did not improve tremor, ataxia, or executive function [22]. However, we found that the N400 repetition effect amplitude, thought to index semantic processing and verbal learning/memory, displayed improvements after the memantine treatment compared with placebo, and predicted verbal learning and memory performance in the FXTAS group (but not in a group with prodromal/early Alzheimer disease) [60,61]. The results suggest that the N400 repetition effect, primarily originating from the temporal neocortex [62,63], is sensitive to memory changes in FXTAS.…”

Section: Discussionmentioning

confidence: 59%

Open-Label Allopregnanolone Treatment of Men with Fragile X-Associated Tremor/Ataxia Syndrome

et al. 2017

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Fragile X-associated tremor/ataxia syndrome (FXTAS) is a late-onset neurodegenerative disorder affecting approximately 45% of male and 16% of female carriers of the FMR1 premutation over the age of 50 years. Currently, no effective treatment is available. We performed an open-label intervention study to assess whether allopregnanolone, a neurosteroid promoting regeneration and repair, can improve clinical symptoms, brain activity, and magnetic resonance imaging (MRI) measurements in patients with FXTAS. Six patients underwent weekly intravenous infusions of allopregnanolone (2-6 mg over 30 min) for 12 weeks. All patients completed baseline and follow-up studies, though MRI scans were not collected from 1 patient because of MRI contraindications. The MRI scans from previous visits, along with scans from 8 age-matched male controls, were also included to establish patients' baseline condition as a reference. Functional outcomes included quantitative measurements of tremor and ataxia and neuropsychological evaluations. Brain activity consisted of event-related potential N400 word repetition effect during a semantic memory processing task. Structural MRI outcomes comprised volumes of the hippocampus, amygdala, and fluid-attenuated inversion recovery hyperintensities, and microstructural integrity of the corpus callosum. The results of the study showed that allopregnanolone infusions were well tolerated in all subjects. Before treatment, the patients disclosed impairment in executive function, verbal fluency and learning, and progressive deterioration of all MRI measurements. After treatment, the patients demonstrated improvement in executive functioning, episodic memory and learning, and increased N400 repetition effect amplitude. Although MRI changes were not significant as a group, both improved and deteriorated MRI measurements occurred in individual patients in contrast to uniform deterioration before the treatment. Significant correlations between baseline MRI measurements and changes in neuropsychological test scores indicated the effects of allopregnanolone on improving executive function, learning, and memory for patients with relatively preserved hippocampus and corpus callosum, while reducing psychological symptoms for patients with small hippocampi and amygdalae. The findings show the promise of allopregnanolone in improving cognitive functioning in patients with FXTAS and in partially alleviating some aspects of neurodegeneration. Further studies are needed to verify the efficacy of allopregnanolone for treating FXTAS.

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Section: Discussionmentioning

confidence: 59%

Open-Label Allopregnanolone Treatment of Men with Fragile X-Associated Tremor/Ataxia Syndrome

et al. 2017

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“…For the final words of the sentences, the FN400 and LPC were analyzed. The components' mean amplitudes for the final words followed by the response time window was qualified based on the findings of the previous literature (e.g., Danko et al, 2014;Molinaro et al, 2016;Yang et al, 2014;Volz et al, 2019) as the mean voltage between 300 to 550 ms…”

Section: The Eeg Recordingmentioning

confidence: 99%

FN400 and LPC Responses to Different Degrees of Sensory Involvement: A Study of Sentence Comprehension

Shayesteh¹,

Pishghadam²,

Khodaverdi³

2020

ACP

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“…The N400 effect is a well-established electrophysiological index of semantic priming and semantic processing load. Yang et al (2014a) have found that the N400 repetition effect amplitude is the strongest predictor of the CVLT short delay cued recall score in patients with FXTAS and was correlated significantly with all 6 CVLT measures of verbal learning and memory in the FXTAS group, but not in a group with prodromal/early AD. These authors suggested that the N400 repetition effect, shown to primarily originate from temporal neocortex ( Nobre et al, 1994 ; Halgren et al, 2002 ), has substantial association with learning/acquisition and short delayed recall, and is sensitive to memory dysfunction in FXTAS.…”

Section: Discussionmentioning

confidence: 93%

Cognitive Deficits and Associated ERP N400 Abnormalities in FXTAS With Parkinsonism

et al. 2018

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Objective: To examine cognitive deficits and associated brain activity in fragile X-associated tremor/ataxia syndrome (FXTAS) patients with parkinsonism (FXTp+), in relation to FXTAS patients without parkinsonism (FXTp-), and normal elderly controls (NC).Methods: Retrospective reviews were performed in 65 FXTAS patients who participated in the event-related brain potential (ERP) study and also had either a videotaped neurological examination or a neurological examination for extrapyramidal signs. Parkinsonism was defined as having bradykinesia with at least one of the following: rest tremor, postural instability, hypermyotonia, or rigidity. Eleven FXTp+ patients were identified and compared to 11 matched FXTp- and 11 NC. Main ERP measures included the N400 congruity effect, N400 repetition effect, and the late positive component (LPC) repetition effect.Results: When compared with FXTp- and NC, the FXTp+ group showed more severe deficits in executive function, cued-recall, recognition memory, along with a significantly reduced N400 repetition effect (thought to index semantic processing and verbal learning/memory) which was correlated with poorer verbal memory. Across all patients, FMR1 mRNA levels were inversely correlated with delayed recall on the California Verbal Learning Test (CVLT).Interpretation: The findings of more prominent executive dysfunction and verbal learning/memory deficits in FXTp+ than FXTp- are consistent with findings in Parkinson’s disease (PD), and may indicate that concomitant and/or synergistic pathogenetic mechanisms associated with PD play a role in FXTAS. These results have implications not only for understanding the cognitive impairments associated with the parkinsonism subtype of FXTAS, but also for the development of new interventions for these patients.

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ERP abnormalities elicited by word repetition in fragile X-associated tremor/ataxia syndrome (FXTAS) and amnestic MCI

Cited by 21 publications

References 46 publications

Open-Label Allopregnanolone Treatment of Men with Fragile X-Associated Tremor/Ataxia Syndrome

Open-Label Allopregnanolone Treatment of Men with Fragile X-Associated Tremor/Ataxia Syndrome

FN400 and LPC Responses to Different Degrees of Sensory Involvement: A Study of Sentence Comprehension

Cognitive Deficits and Associated ERP N400 Abnormalities in FXTAS With Parkinsonism

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