Correlation of Behavioral and Psychological Symptoms and Homocysteine in Patients with Dementia of Alzheimer's Type / 정신신체의학

OBJECTIVES: Homocysteine has been associated with cognitive impairment and various psychiatric symptoms. This study was designed to examine the relationship exists between plasma homocysteine concentration and behavioral and psychological symptoms of dementia(BPSD). METHODS: 41 subjects with dementia of Alzheimer's type were included in this study. We carried out history taking, physical examination, and cognitive assessment for the diagnosis of dementia of Alzheimer's type based on DSM-IV. We scored the Mini Mental State Examination(MMSE), Global Deterioration Scale(GDS), Clinical Dementia Rating(CDR), and the Korean Neuropsychiatric Inventory(K-NPI). We also measured levels of homocysteine, folate, and vitamin B12 in the plasma. RESULTS: We found statistically significant positive correlations between homocysteine concentration with NPI total score, and with scores of several sub-domains such as delusion, agitation/aggression, depression/dysphoria, and elation/euphoria. No significant correlation existed between homocysteine levels and scores of MMSE, GDS, and CDR. CONCLUSIONS: This study shows that plasma homocysteine levels are associated with BPSD. Further research is necessary to identify pathophysiologic mechanisms underlying these relationships.

The Differences of Serum Homocysteine Levels in Mild Cognitive Impairment and Dementia of Alzheimer's Type with or without Depressive Symptoms / 정신신체의학

OBJECTIVES: Mild cognitive impairment(MCI) and dementia of Alzheimer's type(AD) are characterized by progressive decline of cognitive abilities and a wide range of neuropsychiatric symptoms like depression. Among various diagnostic tools of AD, many studies showed that elevated levels of serum total homocysteine are associated with increased risk of developing Alzheimer's disease, depression and other neuropsychiatric disorders. We investigated whether elevated homocysteine concentrations are associated with depressive symptoms in MCI and AD. METHODS: A total of 86 patients diagnosed with MCI or AD participated. Total serum homocysteine levels in fasting blood samples were measured. We examined cognitive symptoms by MMSE-KC, Global Deterioration Scale(GDS), Clinical dementia rating(CDR) and depressive symptoms by Korean version of Geriatric Depression Scale(K-GDS). RESULTS: The total serum homocysteine levels were significantly higher in MCI with depression than in MCI without depression. There was no significant difference in the mean homocysteine levels between AD patients with depression and AD patients without depression. The total homocysteine levels showed a negative correlation with MMSE-KC and a positive correlation with CDR, GDS. CONCLUSIONS: These findings suggest that elevated homocysteine level is a risk factor for the decline of cognitive function and depression. We found a significant relationship between elevated serum homocysteine level and depressive symptoms in MCI. But our study had several limitations, thus more research is needed to confirm this finding.

Features of Semantic Language Impairment in Patients with Amnestic Mild Cognitive Impairment

BACKGROUND: To elucidate the earliest changes of language function in patients with dementia of Alzheimer's type (DAT), performance on the various semantic language tasks were compared between patients with amnestic mild cognitive impairment (aMCI) (n=20), mild DAT (n=20) and normal cognition elderly individuals (NC, n=20). METHODS: Language tasks included levels of word, sentence and discourse. In the word level, confrontation naming test (Korean version-Boston Naming Test, K-BNT) and the verbal fluency (semantic and phonemic fluency) tasks were used. In the sentence level, the verbal definition tasks including 24 nouns four categories were used. In the discourse level, the Boston Cookie-Theft picture description task was used. The picture description task was analyzed for both productive aspect (total number of sentences, total number of phrases and phrases per sentence) and semantic aspect (ratio of CIU: Correct Information Unit). RESULTS: The results from this study are as follow: 1) In the confrontation naming test, mild DAT group showing worse performances than the NC and aMCI group. However, no differences were observed between the NC and aMCI group. 2) The performances of verbal fluency task showed significantly differences between the all groups. 3) In the verbal definition task, performances of NC group showing better performances than aMCI and mild DAT group. However, no differences were observed between the aMCI and mild DAT group. 4) In the picture description task, performances of the aMCI and mild DAT group were non-informative and inefficient in semantic aspect compared to the NC group. However, no differences were observed between the three groups on productive aspect. CONCLUSIONS: These results demonstrated that the deficit of semantic language is readily identified in the aMCI stage, and it can be revealed by tasks of sentence and discourse level.

Neuropsychiatric Symptoms in Patients with Mild Cognitive Impairment and Dementia of Alzheimer's Type / 정신신체의학

OBJECTIVES: We investigated the prevalence and composite score of the neuropsychiatric symptoms in patients with mild cognitive impairment(MCI), and dementia of Alzheimer's type(AD). The aim of this study is to analyze the correlation between the result of Korean Neuropsychiatric Inventory(K-NPI) and cognitive function. METHODS: A total of 163 patients diagnosed with MCI or AD was divided into three groups(55 MCI patients, 56 dementia patients with mild stage, and 52 dementia patients with moderate, severe stage). We examined neuropsychiatric symptoms by K-NPI and compared the prevalence and composite score of each subdomain in K-NPI among three groups. RESULTS: The most common symptoms in the MCI group were depression/dysphoria, sleep/night-time behavior, anxiety, and irritability/lability. In mild AD group, the most frequent disturbance was agitation/aggression, depression/dysphoria, anxiety, apathy/indifference, and sleep/night-time behavior. In moderate to severe AD group, the most frequent disturbance was apathy/indifference, depression/dysphoria, agitation/aggression, and delusion. The frequencies of delusion, hallucination, agitation/aggression, apathy/indifference, aberrant motor behavior, appetite/eating change were statistically significant. The total NPI score showed a negative correlation with MMSE-KC and a positive correlation with GDS. CONCLUSIONS: Neuropsychiatric symptoms are common features of MCI and AD. These symptoms observed in MCI are similar to those of mild AD. Psychosis is most common in moderate to severe AD, leading to a faster rate of cognitive decline. Therefore, proper management according to the neuropsychiatric symptoms of MCI and three stages of dementia is needed.

Power Spectral Analysis of Resting EEG in Elderly Patients With Dementia of Alzheimer and Those With Major Depression in Comparison With Normal Healthy Control

BACKGROUND: Depression is one of the most frequent neuropsychiatric comorbidities of dementia of Alzheimer type (DAT). The aim of the present study was to compare the quantitative EEG changes in patients with DAT with those in old age depression (OAD). METHODS: We recruited 39 subjects (mean age=65.4+/-5.9, 30 women, 13 DAT, 13 OAD, and 13 healthy controls) and performed the absolute and relative power spectral analyses for delta, theta, alpha, and beta activities. RESULTS: The DAT group showed higher frequency of delta in all the topographic areas than the OAD and controls (p<0.05). Delta activity was more frequent in the DAT than OAD group in the bilateral central (C3, C4) and temporal areas (T3, T4) (p<0.05). Compared with the controls, the DAT group showed decreased alpha activity in the left central (C3) and temporal (T3) areas (p<0.05). Beta activity was increased in the OAD group (O1 and O2), compared with that in the other two groups (p<0.05). CONCLUSIONS: Spectral analysis showed more prominent delta slowing in the DAT group, which is in line with more severe cognitive dysfunction in the DAT than the OAD group.

Decreased Plasma Antioxidants Level in Patients with Dementia of Alzheimer's Type / 신경정신의학

OBJECTIVES: Previous studies have suggested that oxidative injuries to the neuron may have important role in the pathophysiologic mechanisms of dementia of Alzheimer's type. In the present study, we evaluate the plasma levels of albumin, total bilirubin, and uric acid in the patients with dementia of Alzheimer's type, and compare to those of the healthy controls. METHODS: The plasma albumin, bilirubin, and uric acid levels were measured by standard methods in 102 patients with dementia of Alzheimer's type (male 42, female 60) and 99 healthy controls (male 47, felmale 52). The Korean version of Mini Mental Status Examination (MMSE-K) was used to evaluate the cognitive functions of patients with dementia of Alzheimer's type. RESULTS: The plasma albumin (F=36.179, p<0.001), bilirubin (F=101.508, p<0.001), uric acid (F=12.688, p<0.001) levels in the patients with dementia of Alzheimer's type were significantly lower than those of the healthy controls. The scores of MMSE-K were positively correlated with the plasma albumin level in the patients with dementia of Alzheimer's type after adjusted for covariates such as age, gender, and body mass index (p=0.017). CONCLUSION: This study supported that oxidative injuries might be involved in the pathogenesis of dementia of Alzheimer's type, as well as suggested that some antioxidant might be associated with the cognitive functions in dementia of Alzheimer's type.

Cerebrovascular Reactivity in Dementia of Alzheimer's Type Assessed by Acetaxolamide Brain SPECT / 신경정신의학

OBJECTIVES: The purpose of this study was to investigate the abnormality of cerebrovascular reactivity in patients with dementia of Alzheimer's type by the acetazolamide brain SPECT, which has been used in the assessment of cerebrovascular diseases. METHODS: Eighteen patients with dementia of Alzheimer's type, as diagnosed by the criteria of DSM-IV and NINCDS-ADRDA, and ten normal comparison subjects were recruited. They were rated by Mini-Mental Status Examination, Mattis Ddementia Rating Scale, and Hamilton Depression Rating Scale. Acetazolamide brain SPECT scans of dementia patients and comparison subjects were analyzed by 3-dimensional volume of interest method. RESULTS: The results were as follows. There were significant differences in the values of cerebrovascular reactivity between the two groups. The cerebrovascular reactivity of dementia patients was significantly decreased in the right frontal lobes, and increased in left temporal lobe, compared to comparison subjects(p<0.05). CONCLUSION: These results imply the possible role of the abnormality of cerebrovascular reactivity in the pathophysiology of dementia of Alzheimer's type.

Longitudinal Study of Cerebral Blood Perfusion Deficits in 12 Cases of Dementia of Alzheimer's Typer / 신경정신의학

OBJECTIVES: The purpose of this study was to investigate the pattern of longitudinal changes in cerebral blood perfusion defects using SPECT in patients with dementia of Alzheimer's type . METHOD: Twelve patients with dementia of Alzheimer's type(10 male, 2 female; mean age 73.25+/- 10.62 years), diagnosed by the criteria of the DSM IV and the NINCDS-ADRDA, and ten normal comparison subjects(7 male, 3 female; mean age 75.10+/-5.76 years) were recruited. They were rated by Mini-Mental Status Examination, Mattis dementia Rating Scale, and Hamilton Depression Rating Scale. rCBF(regional cerebral blood flow) was measured using 99mTc-HMPAO SPECT at the initial study in all subjects, but rCBF was remeasured only in the patients after the follow-up period of average 2 years. SPECT scans of dementia patients and comparison subjects were analyzed by three- dimensional volume of interest method. RESULTS: Results were as follows. 1) There were significant perfusion defects in the bilateral frontal and temporoparietal areas in patients with dementia compared with normal comparison subjects at the baseline evaluation. More extensive perfusion defects including left superior frontal and medial temporal areas were observed in the follow-up SPECT scan compared with baseline scan. 2) There was significant negative correlation between rCBF of bilateral temporal lobe at the baseline scan and the rate of decline of scores of MMSE-K and Mattis dementia rating scale. 3) Various areas of the brain showed correlations between rCBF at the baseline scan and the rate of decline of scores of five subscales of Mattis dementia rating scale. CONCLUSIONS: Three-dimensional VOI approach using SPM analysis showed the characteristic perfusion defects and pattern of longitudinal changes in the patients of dementia of Alzheimer's type, which may be overlooked by the conventional region-of-interest technique. This alteration in rCBF may be closely related to the pathophysiological process of dementia of Alzheimer's type.

Clinical Validity of the Chinese Version of Mattis Dementia Rating Scale in Differentiating Dementia of Alzheimer Type in Shanghai / 中国临床心理学杂志

Objective:To assess clinical validity of the Chinese version of Mattis Dementia Rating Scale (DRS) in differentiating dementia of Alzheimer type (AD). Methods:Administered the DRS, mini-mental state examination (MMSE) and clinical dementia rating(CDR) to 61 outpatients with AD and 104 healthy elderly subjects in Shanghai.Results:There was significant correlation between DRS and the total score,and DRS and MMSE.DRS of the AD group had significant correlation with CDR.Its significant correlation with CDR suggested satisfactory concurrent validity of the scale. The optimal DRS cutoff score for AD according to education level revealed a sensitivity of 85%～94% and a specificity of 90%～94%.Conclusion:The DRS is a clinically valid test for the detection of AD and its severity of cognitive impairment.

Differences in Cognitive Function and Activities of Daily Living between Alzheimer Patients with Depression and Those without Depression / 신경정신의학

OBJECTIVES: Coexistence of depression is one of the important behavioral symptoms in patients with dementia of Alzheimer type. The study on the relationship between depression and cognitive abilities and/or functional abilities emerges as very important one. The aim of this study was to investigate whether depression is related to the impairment of daily activities and to certain areas of cognitive function in mild to moderate dementia of Alzheimer type. METHODS: In this study, 48 patients with dementia of Alzheimer type among elderly community-residents in Kwangju, Kyunggi province, aged 65 and older, were finally included. We examined their demographics and administered Korean Version of the Mini-Mental State Examination(MMSE-K), Korean Version of the Neurobehavioral Cognitive Status Examination(Korean version of NCSE), Korean Form of Geriatric Depression Scale(KGDS), Activities of Daily Living(ADL), and Instrumental Activities of Daily Living(IADL) to the subjects. We classified the subjects into two groups, dementia with and without depression on the basis of KGDS scores. The two groups were compared using X2 test and independent ttest. RESULTS: The results show that the two groups did not differ in sex, age, education, and scores of MMSE-K. The depressed dementia group showed significantly poorer performance in bathing, one item of ADL, than the nondepressed dementia group. The depressed dementia group showed significantly more impairment in total scores of IADL and each score of three items(shopping, housework, handling finances) than the non-depressed dementia group. However, the two groups showed no significant differences in five major cognitive ability areas of Korean version of NCSE. CONCLUSION: These results suggest that depression in patients with dementia of Alzheimer type is highly related to the functional impairments, instrumental activities of daily living and part of activities of daily living, beyond the effects of cognitive impairments.

A preliminary Study for Nonlinear Dynamic Analysis of EEG in Patients with Dementia of Alzheimer

The changes of electroencephalogram(EEG) in patients with dementia of Alzheimer's type are most commonly studied by analyzing power or magnitude in traditionally defined frequency bands. However because of the absence of an identified metric which quantifies the complex amount of information, there are many limitations in using such a linear method. According to the chaos theory, irregular signals of EEG can be also resulted from low dimensional deterministic chaos. Chaotic nonlinear dynamics in the EEG can be studied by calculating the largest Lyapunov exponent(L1). The authors have analyzed EEG epochs from three patients with dementia of Alzheimer's type and three matched control subjects. The largest L1 is calculated from EEG epochs consisting of 16.384 data points per channel in 15 channels. The results showed that patients with dementia of Alzheimer's type had significantly lower L1 than non-demented controls on 8 channels. Topographic analysis showed that the L1 were significantly lower in patients with Alzheimer's disease on all the frontal, temporal, central, and occipital head regions. These results show that brains of patients with dementia of Alzheimer's type have a decreased chaotic quality of electrophysiological behavior. We conclude that the nonlinear analysis such as calculating the L1 can be a promising tool for detecting relative changes in the complexity of brain dynamics.

An Investigation to the Diagnostic Validity of MMSE-K and the Psychopathology in a Group of Urban Patients with Dementia of Alzheimer Type / 신경정신의학

OBJECTIVES: The purpose of present study was to determine the validity of MMSE-K and its items in a group of urban patients with dementia of Alzheimer type and investigate the frequency of psychiatric symptoms and the correlation between the severity of cognitive impairment and that of psychopathology in them. METHODS: The subjects were 107 residents, aged over 55, of an urban community, who participated voluntarily in a free medical service for dementic patients. At first, MMSE-K were administered to all the participients to screen for the cognitive impairment. They were diagnosed mainly by the criteria of DSM-IV for dementia of Alzheimer type. Other diagnostic procedures were performed at that time and these included: a history taking for the past and present medical and psychiatric illnesses of the subject and its family members, physical and neurological examinations, clinical evaluations using several psychiatric symptom rating scales such as BPRS, HDRS, HARS and Overt Aggression Scale, Hachinski's Ishcemic Scale, evaluations for sleep disturbances and behavioral problems in daily living. The majority, of total 72 subjects who were evaluated as having cognitive dysfunctions, were the patients with dementia of Alzheimer type: 52 dementia of Alzheimer type, 12 vascular dementia, one mixed type of the two, and 7 others. We determined the validity of MMSE-K and its items in 52 subjects with dementia of Alzheimer type except the two, who could not respond well to the instructions of MMSE-K due to severe cognitive impairments, and 34 non-dementic subjects with only mild psychiatric symptoms. In 42 subjects with dementia of Alzheimer type who completed all the clinical rating scales with confidence, we investigated the frequency of psychiatric symptoms and the correlation between the severity of cognitive impairment and psychopathology. RESULTS: 1) The percent of false positive in diagnosing dementia of Alzheimer type using MMSE-K was 8.0%, and the sensitivity of MMSE-K was 82% in our 107 urban subjects. 2) There were statistically significant differences in the the mean scores of all items except the item, judgement, between the patients with dementia of Alzheimer type and non-dementic subjects(p<0.05). The two items, orientation for time and place, and the item, copy two pentagons, had the sensitivity and specificity over 70%. 3) The frequencies of behavioral and psychiatric symptoms in 42 patients with dementia of Alzheimer type were as follows: verbal aggression(50.0%), depression(46.2%), insomnia(30.8%), ...... , hallucination(21.2%) and delusion(15.4%). 4) The more cognitive dysfunctions had the patient with dementia of Alzheimer type, the more higher scores in the thinking disturbance subscale of BPRS they showed(p<0.01). CONCLUSION: MMSE-K was proved to be a valid instrument to evaluate the cognitive impairments in patients with dementia of Alzheimer type, but the item, judgement, newly admitted to MMSE-K instead of a language item in MMSE, was proved to be lack of power to discriminate the dementic patient from non-dementic subjects. Our subjects with dementia of Alzheimer type had revealed several behavioral and psychiatric symptoms other than cognitive dysfunctions, and those included depression, anxiety, insommnia, aggression, delusion and hallucination which needed intensive pharmacological interventions.

A Comparison Study on the Psychopathology between the Patients with Dementia of Alzheimer Type and Normal Controls in an Urban Community / 신경정신의학

OBJECT: There are lots of studies on the cognitive impairments in patients with dementia of Alzheimer type in our country, but those on the psychopathology in them are very scanty. We investigated the psychopathology such as psychotic symptoms, depression, and anxiety and their correlations with the severity of cognitive impairments in our urban subjects with dementia of Alzheimer type. METHODS: Our subjects(N=34) with dementia of Alzheimer type in an area of Pusan, aged over 65, are screened with MMSE-K(below 24) and Hachinski's Ischemic Scale(below 4) and enrolled in this study when they met with the criteria of dementia of DSM-IV. They were devided into the mild(N=16) and severe dementic group(N=18) according to their scores of MMSE-K(cut-off point 20/21). The severities of psychiatric symptoms in the two groups were evaluated by using sets of clinical symptom rating scales such as BPRS, HAM-D, and HAM-A and the frequencies of aggressive behaviors and sleep disturbances in them were also rated at that time by two psychiatrists. Data of the two dementic groups were compared with those of healthy control subjects(N=40). RESULTS: The mean total score of BPRS, scores of thinking disturbance and withdrawal retardation subscale were lowest in the healthy control group and highest in the severe dementic group(p<0.05). Mean score of anxious depression subscale of mild dementic group was higher than that of other two groups(p<0.05). There were no ststistical differences in the mean score of hostile suspiciousness subscale among the three groups. The mean total scores of HAM-D and HAM-A tended to be higher in mild dementic group than in other two groups, but the differences were not reached to the statistical significance. These findings were thought to be identical with those of following. The total frequency of insomnia only tended to be higher, but the frequency of initial insomnia and that of using hypnotics were highest in mild dementic group(p<0.05). The frequency of aggressive behaviors tended to be higher in mild dementic group than in other two groups, but the differences were not reached to the statistical significance. CONCLUSION: Patients with dementia of Alzheimer type suffered from several psychiatric problems such as psychotic symptoms, depression, anxiety, insomnia, and aggressive behaviors from the initial stage of the illness. Clinicians should be more aware of those symptoms which need proper pharmacological and social interventions, especially in patients with mild cognitive impairment.

Nonlinear Dynamic Analysis in EEG of Alzheimer's Dementia: A Preliminary Report Using Correlation Dimension

The changes of electroencephalogram(EEG) in patients with dementia are most commonly studied by analyzing power or magnitude in certain traditionally defined frequency bands. However because of the absence of on identified metric which quantifies the complex amount of information, there are many limitations in using such a linear method. According to chaos theory, irregular signals of EEG cal also result from low dimensional deterministic chaos. Chaotic nonlinear dynamics in the EEG can be studied by calculating the correlation dimension. The authors have analyzed EEG epochs from three patients with dementia of Alzheimer type and three matched control subject. The result showed that patients with dementia of Alzheimer type had significantly lower correlation dimension than non-demented controls on 12 channels. Topographic analysis showed that the correlation dimensions were significantly lower in patients with Alzheimer's disease on frontal, temporal, central, and occipital head regions. These results show that brains of patients with dementia with dementia of Alzheimer type have a decreased complexity of electrophysiological behavior. We conclude that the nonlinear analysis such as calculating correlation dimension can be a promising tool for detecting changes in the complexity of brain dynamics.