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Effects of Gender and Apolipoprotein E on Novelty MMN and P3a in Healthy Elderly and Amnestic Mild Cognitive Impairment.

ABSTRACT: Background: The apolipoprotein E epsilon4 (ApoE ?4) allele and female gender may be important risk factors for the development of Alzheimer's disease and amnestic mild cognitive impairment (aMCI). Novelty mismatch negativity (MMN) represents the pre-attentive index of deviance detection and P3a represents the attention orienting response. Furthermore, MMN and P3a components have been reported to be potential markers in aMCI. Therefore, this study will investigate the effects of gender and ApoE on auditory novelty MMN and P3a and their relationship to neuropsychological performance in aMCI. Methods: Thirty nine aMCI subjects and 44 controls underwent neuropsychological assessment and ApoE genotyping. Novelty MMN and P3a components were investigated during an auditory novelty oddball task. Results: Firstly, novelty MMN latency was significantly shorter in aMCI than in healthy control (HC) group. Secondly, novelty MMN latency was negatively correlated with episodic memory in aMCI, but not in HC. Novelty P3a latency was negatively correlated with information processing speed in all subjects. For gender effect, novelty MMN latency was shorter in aMCI females than in HC females. Moreover, novelty P3a amplitudes were lower in males than in females in both aMCI and HC. For the effect of ApoE status, novelty MMN latency was shorter in aMCI ApoE ?4- than HC ApoE ?4-. Conclusion: aMCI presents altered pre-attentive processing indexed by novelty MMN components. Furthermore, there may be a compensatory mechanism on the impaired processing in aMCI. It further suggests that aMCI female and ApoE ?4- recruited the compensatory mechanism.

SUBMITTER: Gao L

PROVIDER: S-EPMC6110901 | biostudies-literature | 2018

REPOSITORIES: biostudies-literature

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Effects of Gender and Apolipoprotein E on Novelty MMN and P3a in Healthy Elderly and Amnestic Mild Cognitive Impairment.

Gao Lijuan L Chen Jiu J Gu Lihua L Shu Hao H Wang Zan Z Liu Duan D Yan Yanna Y Zhang Zhijun Z

Frontiers in aging neuroscience 20180821

<b>Background:</b> The apolipoprotein E epsilon4 (<i>ApoE</i> ε4) allele and female gender may be important risk factors for the development of Alzheimer's disease and amnestic mild cognitive impairment (aMCI). Novelty mismatch negativity (MMN) represents the pre-attentive index of deviance detection and P3a represents the attention orienting response. Furthermore, MMN and P3a components have been reported to be potential markers in aMCI. Therefore, this study will investigate the effects of gen ...[more]

PMID: 30186155

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Project description:The event-related potential (ERP) technique has been shown to be useful for evaluating changes in brain electrical activity associated with different cognitive processes, particularly in Alzheimer's disease (AD). Longitudinal studies have shown that a high proportion of people with amnestic mild cognitive impairment (aMCI) go on to develop AD. aMCI is divided into two subtypes according to the presence of memory impairment only (single-domain aMCI: sdaMCI) or impairment of memory and other cognitive domains (multi-domain aMCI: mdaMCI). The main aim of this study was to examine the effects of sdaMCI and mdaMCI on the P3a ERP component associated with the involuntary orientation of attention toward unattended infrequent novel auditory stimuli. Participants performed an auditory-visual distraction-attention task, in which they were asked to ignore the auditory stimuli (standard, deviant, and novel) and to attend to the visual stimuli (responding to some of them: Go stimuli). P3a was identified in the Novel minus Standard difference waveforms, and reaction times (RTs) and hits (in response to Go stimuli) were also analyzed. Participants were classified into three groups: Control, 20 adults (mean age (M): 65.8 years); sdaMCI, 19 adults (M: 67 years); and mdaMCI, 11 adults (M: 71 years). In all groups, the RTs were significantly longer when Go stimuli were preceded by novel (relative to standard) auditory stimuli, suggesting a distraction effect triggered by novel stimuli; mdaMCI participants made significantly fewer hits than control and sdaMCI participants. P3a comprised two consecutive phases in all groups: early-P3a (e-P3a), which may reflect the orienting response toward the irrelevant stimuli, and late-P3a (l-P3a), which may be a correlate of subsequent evaluation of these stimuli. The e-P3a amplitude was significantly larger in mdaMCI than in sdaMCI participants, and the l-P3a amplitude was significantly larger in mdaMCI than in sdaMCI and Control participants, indicating greater involuntary capture of attention to unattended novel auditory stimuli and allocation of more attentional resources for the subsequent evaluation of these stimuli in mdaMCI participants. The e-P3a and l-P3a components showed moderate to high sensitivity and specificity for distinguishing between groups, suggesting that both may represent optimal neurocognitive markers for differentiating aMCI subtypes.

Project description:IntroductionLipoprotein-associated phospholipase A2 (Lp-PLA2) is a circulating enzyme with pro-inflammatory and oxidative activities associated with cardiovascular disease and ischemic stroke. While high plasma Lp-PLA2 activity was reported as a risk factor for dementia in the Rotterdam study, no association between Lp-PLA2 mass and dementia or Alzheimer's disease (AD) was detected in the Framingham study. The objectives of the current study were to explore the relationship of plasma Lp-PLA2 activity with cognitive diagnoses (AD, amnestic mild cognitive impairment (aMCI), and cognitively healthy subjects), cardiovascular markers, cerebrospinal fluid (CSF) markers of AD, and apolipoprotein E (APOE) genotype.MethodsSubjects with mild AD (n = 78) and aMCI (n = 59) were recruited from the Memory Clinic, University Hospital, Basel, Switzerland; cognitively healthy subjects (n = 66) were recruited from the community. Subjects underwent standardised medical, neurological, neuropsychological, imaging, genetic, blood and CSF evaluation. Differences in Lp-PLA2 activity between the cognitive diagnosis groups were tested with ANOVA and in multiple linear regression models with adjustment for covariates. Associations between Lp-PLA2 and markers of cardiovascular disease and AD were explored with Spearman's correlation coefficients.ResultsThere was no significant difference in plasma Lp-PLA2 activity between AD (197.1 (standard deviation, SD 38.4) nmol/min/ml) and controls (195.4 (SD 41.9)). Gender, statin use and low-density lipoprotein cholesterol (LDL) were independently associated with Lp-PLA2 activity in multiple regression models. Lp-PLA2 activity was correlated with LDL and inversely correlated with high-density lipoprotein (HDL). AD subjects with APOE-ε4 had higher Lp-PLA2 activity (207.9 (SD 41.2)) than AD subjects lacking APOE-ε4 (181.6 (SD 26.0), P = 0.003) although this was attenuated by adjustment for LDL (P = 0.09). No strong correlations were detected for Lp-PLA2 activity and CSF markers of AD.ConclusionPlasma Lp-PLA2 was not associated with a diagnosis of AD or aMCI in this cross-sectional study. The main clinical correlates of Lp-PLA2 activity in AD, aMCI and cognitively healthy subjects were variables associated with lipid metabolism.

Dataset Information

Effects of Gender and Apolipoprotein E on Novelty MMN and P3a in Healthy Elderly and Amnestic Mild Cognitive Impairment.

Publications

Effects of Gender and Apolipoprotein E on Novelty MMN and P3a in Healthy Elderly and Amnestic Mild Cognitive Impairment.

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