Article

Absent event-related potential (ERP) word repetition effects in mild Alzheimer's disease.

Department of Neurosciences, University of California, San Diego, CA 92161, USA.
Clinical Neurophysiology (Impact Factor: 2.98). 07/2006; 117(6):1319-30. DOI: 10.1016/j.clinph.2006.02.022
Source: PubMed

ABSTRACT We hypothesized that an ERP word repetition paradigm, which reliably elicits and modulates the P600 and N400 components, would be particularly sensitive to the memory deficits and altered synaptic plasticity in mild Alzheimer's disease (AD). The P600 (a late positive component, or 'LPC'), and the N400, are sensitive indices of memory encoding and semantic processing, respectively.
We studied 11 patients with mild AD (mean MMSE=22.9) and 11 elderly (mean age=77.1) normal controls (NC) on a paradigm in which semantically 'congruous' category statement/exemplar pairs (50%) and 'incongruous' category statement/non-exemplar pairs (50%) repeat at 10-140 s intervals. A minimum of 19 channels ERP data were recorded and submitted to split-plot ANOVAs.
Normal ERP data showed: (1) a significant word repetition effect for congruous words, with a wide-spread late positivity between approximately 300 and 800 ms post-stimulus (P600) that is larger for New than Old words; (2) a significant N400 repetition effect for incongruous words, with a right posterior negativity that is reduced for Old relative to New words. By contrast, neither of these word repetition effects was reliably present in the mild AD group. Good group discrimination was achieved by requiring that both these repetition effects were > or = the 10th percentile, with 100% sensitivity and 82% specificity.
We found significant abnormalities of the N400 and P600 in mild AD, with both potentials showing markedly reduced sensitivity to word repetition.
The absence of normal N400 and LPC/P600 word repetition effects suggests impaired functioning of their neural generators, several of which are located in medial temporal lobe predilection sites (e.g. anterior fusiform, parahippocampal gyrus, hippocampus) for AD/tau pathology.

0 Bookmarks
 · 
111 Views
  • [Show abstract] [Hide abstract]
    ABSTRACT: Background Fragile X-associated tremor/ataxia syndrome (FXTAS), a neurodegenerative disorder caused by FMR1 gene premutations, typically associated with frontal-subcortical type cognitive impairments. High prevalence (~50%) of superimposed Alzheimer's pathology has been reported in FMR1 premutation carriers, and standardized neuropsychological tests have not yielded any robust discriminators between FXTAS and Alzheimer's disease (AD) dementia. The similarities/differences in memory processes between FXTAS and early AD remain underexplored. Methods 32-channel event-related potentials (ERPs) were obtained from a semantic judgment task in which semantically congruous (50%) and incongruous pairs repeat pseudorandomly. The N400 and late positive component (LPC) of 25 FXTAS patients (Mage=71.2, MMSE=26.6) were compared to a matched group of 25 patients with MCI or early AD (1 mild AD dementia, 24 amnestic MCI, of whom 18 later converted to AD; Mage=73.4, MMSE=26.4), and 25 healthy elderly. Results Both patient groups showed similar reductions in the N400 repetition effect and N400 congruity effect amplitudes, compared to controls, reflecting abnormal semantic priming and repetition priming. The MCI/AD group, however, had significantly smaller LPC word repetition effects and poorer learning and memory on the CVLT than FXTAS. The LPC and N400 repetition effects both correlated with verbal memory across all subjects, but only the N400 correlated with memory in FXTAS. Conclusion FXTAS patients show relative sparing of the LPC repetition effect, and less disruption of explicit memory than prodromal/early AD. N400 abnormalities in FXTAS appear to account for much of their mild impairments in verbal learning and memory.
    Neuropsychologia 10/2014; · 3.45 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: The fragile X-associated tremor/ataxia syndrome (FXTAS) is a late-onset neurodegenerative disorder affecting a subset of carriers of the FMR1 (fragile X mental retardation 1) premutation. Penetrance and expression appear to be significantly higher in males than females. Although the most obvious aspect of the phenotype is the movement disorder that gives FXTAS its name, the disorder is also accompanied by progressive cognitive impairment. In this review, we address the cognitive neuropsychological and neurophysiological phenotype for males and females with FXTAS, and for male and female unaffected carriers. Despite differences in penetrance and expression, the cognitive features of the disorder appear similar for both genders, with impairment of executive functioning, working memory, and information processing the most prominent. Deficits in these functional systems may be largely responsible for impairment on other measures, including tests of general intelligence and declarative learning. FXTAS is to a large extent a white matter disease, and the cognitive phenotypes observed are consistent with what some have described as white matter dementia, in contrast to the impaired cortical functioning more characteristic of Alzheimer's disease and related disorders. Although some degree of impaired executive functioning appears to be ubiquitous among persons with FXTAS, the data suggest that only a subset of unaffected carriers of the premutation - both female and male - demonstrate such deficits, which typically are mild. The best-studied phenotype is that of males with FXTAS. The manifestations of cognitive impairment among asymptomatic male carriers, and among women with and without FXTAS, are less well understood, but have come under increased scrutiny.
    Journal of Neurodevelopmental Disorders 01/2014; 6(1):28. · 3.71 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: ABSTRACT There is a marked lack of consensus concerning the best way to learn how conscious experiences arise. In this article, we advocate for scientific approaches that attempt to bring together four types of phenomena and their corresponding theoretical accounts: behavioral acts, cognitive events, neural events, and subjective experience. We propose that the key challenge is to comprehensively specify the relationships among these four facets of the problem of understanding consciousness without excluding any facet. Although other perspectives on consciousness can also be informative, combining these four perspectives could lead to significant progress in explaining a conscious experience such as remembering. We summarize some relevant findings from cognitive neuroscience investigations of the conscious experience of memory retrieval and of memory behaviors that transpire in the absence of the awareness of remembering. These examples illustrate suitable scientific strategies for making progress in understanding consciousness by developing and testing theories that connect the behavioral expression of recall and recognition, the requisite cognitive transactions, the neural events that make remembering possible, and the awareness of remembering.
    Perspectives on Psychological Science 03/2009; · 4.89 Impact Factor

Preview

Download
0 Downloads
Available from