The Role Of Auditory Event-related Potentials And Magnetic Resonance Spectroscopy Measures In Diagnosis Of Mild Cognitive Impairment

There are many reasons for elderly dementia, Alzheimer’s disease (AD) is the most common.Widespread cognitive decline appear gradually,seriously affecting the quality of life of older persons.Mild cognitive impairment (MCI) is a disorder in older patients that is initially characterized by cognitive disturbances,such as memory or language function that is a major risk factor for AD.MCI has been paid more attention as an independent disease.MCI patients are at high risk of conversion to AD.It is a long development process between healthy elderly and AD.Because there are no effective treatment on AD, MCI is the intervention stage, has become the focus of research.Auditory event-related potential (AERPs) is a reliable non-invasive detection of nerve electrophysiology to identify cognitive impairment and mental state assessment.Magnetic resonance spectroscopy (MRS) is a non-invasive neural imaging technology to analyze brain metabolites in vivo.This study was aimed to examine the AERPs and 1H-MRS characteristic changes of MCI, to examine the changes in AERPs and their relationship with brain metabolic changes in MCI by analyzing the results of controls,MCI and AD subjects.By examining AERPs and brain biochemical components, We observe the changes of these parameters in MCI subjects in order to find neuroelectrophysiological indexes to reflect cognitive impairment in earlier period of MCI.We analyzed the correlation of AERPs components abnormalities and the biochemical components abnormalities in different brain regions,and the correlation of abnormalities in AERPs and 1H-MRS with the clinical cognitive test scores.We study their relationship in order to find the early metabolic abnormalities of different brain regions that may reflect the changes of brain activities in the MCI.We study the relationship of abnormalities in AERPs and 1H-MRS with the clinical cognitive test scores in order to identify concordance of these changes, identify the role of AERPs and 1H-MRS measurements.They may offer means to diagnosis MCI and track changes of brain activities associated with functional and metabolic changes,and to assess early cognitive impairment in MCI.Combined 1H-MRS and AERPs can improve diagnostic accuracy of MCI.METHODS1.The study involve MCI,mild AD patients and age-matched healthy elderly control subjects.MCI group,34 patients,23 males and 11 females,aged 62 to 85 years,mean age 71.6±5.7 years,years of education 7.8±1.2 years.AD group,18 patients,11 males and 7 females,aged 60 to 83 years,mean 73.4±5.6 years,years of education 7.1±1.4 years.The control group 34 patients,21 males and 13 females,aged 57 to 80 years,mean age 71.6±5.7 years,years of education 7.8±1.2 years.The cognitive functions of the all subjects were assessed by clinical neurological and neuropsychological assessment scales in overall cognitive function,memory function,language function, executive function and visual spatial function.2.After neuropsychological assessments,the event related potentials components P50,N100,P200,N200 and P300 waves of the subjects evoked by a sonic stimulus Oddball mode,a target detection task by listening to a sequence of tones.The stimulus paradigm were recorded in MCI,mild AD and control subjects.We analyzed group differences of P50,N100,P200 latencies and amplitudes recorded at the Cz site;N200 and P300 waves latencies and amplitudes differences recorded at the Pz site.3.Brain metabolic data were collected three days after AERPs were examined in all subjects.The concentrations of brain metabolites and the metabolite ratios were obtained in three different brain areas:left frontal,left temporal and right parietal cortex by magnetic resonance spectroscopy.The brain metabolites were N-acetyl aspartate (NAA),Creatine (Cr) and Choline (Cho).The metabolite ratios were NAA/Cr and NAA/Cho.We analyzed group differences in MCI,mild AD and control subjects.4.We analyzed correlation between AERPs parameters and cerebral NAA/Cr ratios in left frontal and left temporal lobe cortex of MCI.AERPs parameters were P50 amplitude and P300 latency.We analyzed the diagnostic accuracy of P50 amplitude,P300 latency,NAA/Cr of left frontal and left temporal cortex to MCI.5.We correlate P50,N100,P200,N200,P300 latencies and amplitudes with clinical neuropsychological scores of MCI.6.We correlate cerebral NAA/Cr ratios in left frontal,left temporal lobe and right parietal cortex with clinical neuropsychological scores of MCI.7.Statistical analysis:Data are expressed as mean±SD.SPSS16.0 software was used for statistical analysis.One way ANOVA was used with the LSD multiple comparison tests for multiple groups;Pearson correlation was used for correlation analysis;linear regression was used for regression analysis.We drew receiver operating characteristic curve according to the results of individual detection and combined detection,calculated area under the curve and standard error.Statistical significance was accepted at a level of P < 0.05.RESULTS1. Neuropsychological analysis of MCIMCI received significantly lower scores in all memory tests and one of the language test Boston naming test(P< 0.001 or P< 0.0001.MCI and controls showed no significant differences in the results of another language test verbal fluency test,the two visual-spatial function tests and the two executive function tests(all P>0.05.AD patients had significantly lower scores in all tests(P< 0.05 or P< 0.0001).2. Auditory event-related potentials analysis of MCI(1)In response to non-targetsAERPs in response to non-target frequent tones at the Cz site are presented.P50 amplitude in MCI were significantly increased than controls(P< 0.001).But there were no significant group differences in the latency of P50, amplitudes or latencies of N100 and P200(all P>0.05).AD had significant lower amplitude than MCI(P< 0.05).(2)In response to target infrequent tonesMCI showed a significantly prolonged P300 latency and lowered amplitude than controls(all P< 0.05).But there were no significant group differences in the N200 latency and amplitude(all P>0.05.AD had significantly prolonged P300 latency and lowered amplitude than MCI(all P< 0.01).But there were no significant group differences in the N200 latency and amplitude(all P>0.05).3. Metabolite levels and ratios analysis of MCI by 1H-MRSThe levels of metabolites NAA,Cr,Cho and their ratios NAA/Cr, Cho/Cr in left frontal, left temporal and right parietal cortex of controls,MCI and AD patients are shown.Compared with controls, MCI had significant lower NAA and NAA/Cr in the left prefrontal and left temporal cortex(P< 0.05 or P< 0.01), but not in the right parietal cortex.Cr,Cho and Cho/Cr were not significantly different between groups in three brain areas(all P>0.05).AD patients had significantly decreased NAA and NAA/Cr in the left prefrontal,left temporal and right parietal cortex than MCI(all P< 0.0001).But there were no significant group differences of Cr,Cho and Cho/Cr in three brain areas(all P>0.05).4. Relationship between AERPs , 1H-MRS and cognitive tests of MCI P50 amplitude and P300 latency were negatively correlated with all the memory scores of MCI.NAA/Cr in the left prefrontal and left temporal cortex were positively correlated with all the memory scores of MCI.P50 amplitude was negatively correlated with NAA/Cr in the left prefrontal cortex; P300 latency was negatively correlated with NAA/Cr in the left prefrontal and left temporal cortex.The receiver operating characteristic curve showed the largest area under the curve when P50 amplitude, P300 latency, NAA / Cr of left frontal and left temporal cortex were combined in identifying NC and MCI, MCI and AD.CONCLUSIONS1. MCI had obvious disorders of assessment of memory function, had slightly partial damage in assessment of language function.There were no obvious impairment of executive function and visual-spatial function.These results consistent with the cognitive characteristics of MCI.2. MCI had larger P50 amplitude and prolonged P300 latency.AD had more prolonged P300 latency than MCI.P50 amplitude and P300 latency may be used to identify normal, MCI and AD.3. MCI had significantly lower NAA/Cr ratios.AD had lower NAA/Cr ratios and more brain areas affected than MCI.NAA / Cr can be used to identify normal, MCI and AD.4. P50 amplitude ,P300 latency and NAA/Cr were correlated with scores of clinical memory tests of MCI.Combined 1H-MRS and AERPs can improve significantly diagnostic accuracy of MCI.Combined AERPs and 1H-MRS may be used as a means of diagnosis and follow-MCI.P50 amplitude and P300 latency were correlated with NAA/Cr.