Noropsychological factors associated with mismatch negativity in dementia patients, mild cognitive impairment patients and in healthy elderly

Introduction and Objective: Dementia is a neurodegenerative disease that causes disability with an increased incidence gradually both in our country and worldwide. The most common type of dementia is the one due to Alzheimer's Disease (AD) and mild cognitive impairment (MCI) is accepted as the prodromal phase of AD. Every year, %10-15 of the MCI cases progress to dementia. Both in AD and in MCI phase, some neuropsychiatric symptoms are seen in addition to the impairment in memory and the cognitive functions. It is considerably valuable to be able to detect the AD by a sensible, cheap and non-invasive method in the MCI phase in order to determine the neuropathological changes before the cognitive impairments are seen in the clinical phase. In this study, it is aimed to investigate if there is a difference in mismatch negativity wave which is a non-invasive electrophysiological method, neuropsychiatric symptoms and neuropsychiatric tests in AD, MCI and healthy elder group, and examine if MMN can be used as a biomarker to distinguish three groups from each other. Material and method: 21 mild AD, 26 aMCI and 18 healthy control cases matched according to age, sex and educational level were compared in terms of the sociodemographic data, neuropsychological test performances, neuropsychiatric inventory scores, functional activity and MMN parameters. In order to evaluate the cognitive functions, revised Turkish version of Mini Mental State Examination (rMMSE-T) for educated elderly; to evaluate the memory, auditory verbal learning test; to evaluate the executive function, Stroop test, KAS verbal fluency test and trail making test; to evaluate the functional activity, basic and instrumental activities of daily living scale; to detect the vascular risk factors and to distinguish AD from the vascular dementia, Hachinski ischemia score; to evaluate the neuropsychiatric symptoms, neuropsychaitric inventory; to evaluate the depressive symptoms, geriatric depression scale and Cornell scale of depression in dementia was applied. After this evaluation, 50 ms tone burst auditory stimuli with 10 ms rise/fall was given in a random sequence binaurally to all groups by using auditory oddball paradigm with an interstimulan interval of 1 second, the frequency of the standard stimuli was 80% ( 80 db, 1000 Hz) and the frequency of the deviant stimuli was 20% ( 80 db, 2000 Hz) and it was recorded from the Fz, Cz, Pz, C3, C4, T5 and T6 electrodes. Results: AD patients were considerably older than the other groups and the family history for dementia was higher in AD patients. The deterioration in basic activities of daily living (BADL) scale was most frequent in AD, then in MCI, and least frequent in healthy group; the deterioration in instrumental activities of daily living (IADL) scale was most frequent in AD whileIADL scores of MCI and healthy groups were similar. Depression scores of AD and MCI were similar and higher than healthy group. MMSE and clock drawing test (CDT) performances of MCI cases were considerably better than AD but worse than healthy group. Trail Making Test and verbal fluency test performances were lowest in AD and similar in MCI and healthy groups. Stroop 4 test performance was similar in MCI and AD and they completed the test in a longer time compared to healthy group. Stroop 5 test performance was lowest in AD, MCI had a better performance and healthy group had the best performance. For RAVLT A2-3-4-6 (free recall)-7 (delayed free recall) and A+B (recognition recall) tests, the best performance was shown by healthy group, then by MCI and then by AD. Only A5 free recall test performance was equal in MCI and healthy group. Agression scores were highest in MCI group while dysphoria, apathy, irritability and total NPI scores were higher in the MCI and AD groups than healthy group. MMN amplitude in the frontal region was similar in MCI and healthy group and was significantly higher than AD (lowest in AD); but there was no difference between the three groups in terms of amplitude in other regions. There was no difference between the three groups in terms of latencies. There was a positive correlation between the T5 amplitude and verbal learning, free recall, delayed recall and MMSE score in all sample and in MCI and AD groups seperately. In the whole sample, the prolongation of Stroop test times was found to be related to reduced amplitude and increased latency in central locations. There was a positive correlation between verbal fluency test performance and temporal MMN amplitude while a negative correlation was found between trail making test performance and temporocentral MMN amplitudes. Apathy was the most related neuropsychiatric symptom with executive functions. In the lineer regression analysis, instrumental daily living activities were found to be predicted by fz amplitude, SMMT total and apathy in all sample. Logistic regression analysis in all sample revealed that geriatric depression scale score and verbal fluency K subtest score distinguished Alzheimer's patients from healthy group, while Stroop 5 and NPI total score distinguished MCI cases from healthy group and age and Fz amplitude distinguished AD patients from MCI patients. Discussion : In present study, reduced amplitude in Fz and Cz electrodes seen in AD patients compared to healthy group even in the short interstimulus interval may reveal that these patients might have a problem in frontocentral activation. The reduced MMN amplitude in the frontal region in AD may reflect impaired pre-attentional processes and distractibility in these patients. The fact that latencies were not different between the groups may be due to the short interstimulus interval of 1 second. In addition, the increased amplitude in the frontal region detected in MCI cases may reflect a compensatory effort against distractibility. Conclusion: MMN might be a candidate biomarker to differentiate AD from MCI and healthy group if used together with neuropsychological tests and neuropsychiatric inventory rather than being used alone since, it may be affected from confounding factors. It will be useful to conduct new prospective follow-up studies in the future with larger sample sizes, different interstimulan intervals and different biomarkers to evaluate the transformation from MCI to AD in the long term.