Association between Olfactory Deficit and Motor and Cognitive Function in Parkinson’s Disease

Objective@#To investigate whether baseline olfactory dysfunction in Parkinson’s disease (PD) patients is associated with baseline and longitudinal motor and cognitive function. @*Methods@#We recruited 228 drug-naïve PD patients who were followed for a mean of 6 years. Patients underwent the Cross-Cultural Smell Identification Test (CCSIT), a neuropsychological test, and N-(3-[18F]fluoropropyl)-2β-carbomethoxy-3β-(4-iodophenyl) nortropane positron emission tomography within 6 months of the baseline evaluation. Olfactory dysfunction was categorized as normosmia (CCSIT score ≥ 9), hyposmia (CCSIT score 5–8), and anosmia (CCSIT score ≤ 4). During the follow-up period, we investigated changes in the levodopa-equivalent dose (LED) and the occurrence of wearing-off, levodopa-induced dyskinesia, and dementia. @*Results@#Among the PD patients, 80.7% were hyposmic at the time of diagnosis, and 26.1% were anosmic. Baseline olfactory dysfunction was not associated with either initial parkinsonian motor symptoms or with the longitudinal LED increment and motor complications. Meanwhile, the anosmic group had lower baseline scores on the Korea version of the Boston Naming Test and Stroop color reading test than the normosmic and hyposmic groups. The anosmic group exhibited a higher rate of conversion to dementia than the normosmic [adjusted hazard ratio (HR) 3.99, 95% confidence interval (CI) 1.08–14.72] and hyposmic (adjusted HR 2.48, 95% CI 1.15–5.32) PD groups, regardless of baseline motor deficits and cognitive status. @*Conclusion@#Baseline olfactory dysfunction was not associated with motor deficits and complications, but it was associated with cognitive dysfunction and prognosis, suggesting that severe olfactory impairment may reflect early cortical involvement, probably in the frontotemporal region, and rapid spreading of Lewy body pathology.

Heterogeneous Patterns of Striatal Dopamine Loss in Patients with Young- versus Old-Onset Parkinson's Disease: Impact on Clinical Features

OBJECTIVE: Ample evidence has suggested that age at onset of Parkinson's disease (PD) is associated with heterogeneous clinical features in individuals. We hypothesized that this may be attributed to different patterns of nigrostriatal dopamine loss. METHODS: A total of 205 consecutive patients with de novo PD who underwent 18F-FP-CIT PET scans (mean follow-up duration, 6.31 years) were divided into three tertile groups according to their age at onset of parkinsonian motor symptoms. Striatal dopamine transporter (DAT) availability was compared between the old- (n = 73) and young-onset (n = 66) groups. In addition, the risk of developing freezing of gait (FOG) and longitudinal requirements for dopaminergic medications were examined. RESULTS: The old-onset PD group (mean age at onset, 72.66 years) exhibited more severe parkinsonian motor signs than the young-onset group (52.58 years), despite comparable DAT availability in the posterior putamen; moreover, the old-onset group exhibited more severely decreased DAT availability in the caudate than the young-onset group. A Cox regression model revealed that the old-onset PD group had a higher risk for developing FOG than the young-onset group [hazard ratio 2.523, 95% confidence interval (1.239–5.140)]. The old-onset group required higher doses of dopaminergic medications for symptom control than the young-onset group over time. CONCLUSION: The present study demonstrated that the old-onset PD group exhibited more severe dopamine loss in the caudate and were more likely to develop gait freezing, suggesting that age at onset may be one of the major determinants of the pattern of striatal dopamine depletion and progression of gait disturbance in PD.

Risk Factors for Vancomycin-Associated Nephrotoxicity in Elderly Patients

OBJECTIVE: Infection is very common in the elderly, so there is a high prevalence of antibiotics use among this population. Especially, due to the emergence of resistant bacteria, the use of vancomycin is growing. The purpose of this study was to evaluate risk factors associated with vancomycin-induced nephrotoxicity in elderly patients. METHODS: The subjects of this study were patients over 18 years old who received intravenous vancomycin in a general hospital located in Gangneung-si, Korea between August 1, 2013 and July 31, 2015. Data collection regarding vancomycin use and baseline characteristics was conducted using computerized hospital database. Logistic regression analysis was used to identify risk factors associated with vancomycin-induced nephrotoxicity. RESULTS: A total of 290 patients were finally included, and 191(66%) out of these patients were age 65 or older. The incidence of vancomycin-induced nephrotoxicity was 11.0%, 12.6%, and 7.0% in the all adult patients, the elderly patients, and the non-elderly patients, respectively. There were significant differences in comorbidities between patients with nephrotoxicity and patients without nephrotoxicity in the all adult patients, and there were significant differences in vancomycin duration, comorbidities, and number of nephrotoxic agents between patients with nephrotoxicity and patients without nephrotoxicity in the elderly patients. However, according to the logistic regression analysis, there was no significant risk factor that increases the incidence of vancomycin-induced nephrotoxicity in all three age groups. CONCLUSION: There were no differences in risk factors that increase the incidence of vancomycin-induced nephrotoxicity between all adult patients, elderly patients, and non-elderly patients. Further studies with larger sample sizes to identify risk factors associated with vancomycin-induced nephrotoxicity in the elderly to improve the outcome of pharmacotherapy are required.

Cardiovascular Autonomic Dysfunction in Patients with Drug-Induced Parkinsonism

BACKGROUND AND PURPOSE: Recent studies have shown that several nonmotor symptoms differ between Parkinson's disease (PD) and drug-induced parkinsonism (DIP). However, there have been no reports on cardiovascular autonomic function in DIP, and so this study investigated whether cardiovascular autonomic function differs between PD and DIP patients. METHODS: This study consecutively enrolled 20 DIP patients, 99 drug-naïve PD patients, and 25 age-matched healthy controls who underwent head-up tilt-table testing and 24-h ambulatory blood pressure monitoring. RESULTS: Orthostatic hypotension was more frequent in patients with PD or DIP than in healthy controls. In DIP, orthostatic hypotension was associated with the underlying psychiatric diseases and neuroleptics use, whereas prokinetics were not related to orthostatic hypotension. The supine blood pressure, nighttime blood pressure, and nocturnal blood pressure dipping did not differ significantly between the DIP and control groups. Supine hypertension and nocturnal hypertension were more frequent in PD patients than in controls. CONCLUSIONS: The included DIP patients frequently exhibited orthostatic hypotension that was associated with the underlying diseases as well as the nature of and exposure time to the offending drugs. Clinicians should individualize the manifestations of DIP according to underlying diseases as well as the action mechanism of and exposure time to each offending drug.

Bilateral Thalamic Lesions in Hashimoto's Encephalopathy

No abstract available.

Neural Differentiation of Bone Marrow-Derived Mesenchymal Stem Cells: Applicability for Inner Ear Therapy

BACKGROUND AND OBJECTIVES: Regeneration or replacement of damaged hair cells and neurons in the cochlea might be an ideal treatment for sensorineural hearing loss (SNHL). The purpose of the present study was to investigate whether mesenchymal stem cells (MSCs), derived from the bone marrow of rats, could differentiate into auditory hair cells and neurons. MATERIALS AND METHODS: The centrifuge gradient method was used to isolate MSCs from the bone marrow of rats. To confirm whether bone marrow-derived MSCs can differentiate into neuronal cells, culture medium with glial cell-derived neurotrophic factor, brain-derived neurotrophic factor and neurotrophin-3 for 14 days. In addition, immunofluorescence staining and RT-PCR were performed for characterization of the neurospheres and differentiated cells from 7 and 14 day cultures. RESULTS: The results showed that MSCs could differentiate into neuron-positive and hair cell-positive cells, using different compositions of growth factors. And RT-PCR result was identified high or low of gene expression all these differentiated cells. CONCLUSIONS: Rat bone marrow-derived MSCs differentiated into neuronal progenitor cells. These cells might be useful for the treatment of SNHL.

A Validation Study for the Korean Version of Delirium Rating Scale-Revised-98 (K-DRS-98) / 신경정신의학

OBJECTIVE: This study was conducted to develop and to validate the Korean version of Delirium Rating Scale-Revised-98 (K-DRS-98), which is a scale for diagnosing delirium and evaluating its severity. METHOD: After developing the K-DRS-98, 102 patients were rated by it among 4 diagnostic groups, such as delirium (N=25), dementia (N=27), schizophrenia (N=25) and others (N=25). To test for reliability, K-DRS-98 was independently administered by two psychiatrist. To test for validity, Korean version of Mini-Mental State Examination (MMSE-K) and Clinical Global Impression (CGI) were administered simultaneously. Statistical analysis was done with SPSS window version 12 package and statistical significance was p<0.05. RESULT: Internal consistencies (Cronbach alpha) of two raters were 0.867 and 0.858, respectively. Inter-rater reliability (kappa) was 0.893 for severity items of K-DRS-98 and kappa value of diagnosis items was 0.969. In Delirium group, Pearson correlation coefficients (gamma) of K-DRS-98 were -0.682 for MMSE-K and 0.667 for CGI. In comparison Delirium group with Others, ANOVA post hoc multiple comparison LSD was statistically significant (p<0.001). The cutoff score to diagnosis of delirium can be recommended 16 for severity items and 21.5 for total score, respectively. CONCLUSION: The K-DRS-98 was showed good reliability and validity for the assessment of delirium. The K-DRS-98 is an easy and useful tool for diagnosing delirium and assessing its severity.

Effectiveness and Tolerability of Long-Acting Risperidone: A 12 Weeks, Multi-center Switching Study from Oral Antipsychotics / 대한정신약물학회지

OBJECTIVE: To evaluate maintained effectiveness and tolerability when treated with long-acting risperidone compared to the previous antipsychotics in patients with schizophrenia or other psychotic disorders and to compare maintained effectiveness between oral risperidone and non-risperidone subgroups. METHODS: Subjects aged at least 18 years who required long-term antipsychotic therapy and who have been symptomatically stable on a stable dose of antipsychotics during the last month were enrolled in the non-randomized, single-arm, multi-center, 12 weeks duration study. Antipsychotic medications were switched from oral antipsychotics to long-acting risperidone. Injections were administered every 2 weeks. Most patients were started on 25mg long-acting risperidone injection or 37.5mg in some patients. The dosage were adjusted according to the patients' symptoms and responses to treatment at the discretion of investigators. Oral antipsychotics were continued at the same dose as before for 2 weeks and then were stopped or tapered off within next 7days. RESULTS: A total of 204 patients with schizophernia (N=192) and other psychotic disorder (N=12) from 20 sites in Korea were enrolled. The drop-out rate was 22.5% at 12 weeks. LOCF analysis has been performed. At 12 weeks after switching from oral antipsychotics to long-acting risperidone, statistically significant improvement was observed from baseline across all symptom domains including PANSS total, positive, negative, general subscale, CGI-S (Clinical Global Impression-Severity) scores and GAF (Global Assessment of Functioning) scores. The proportion of responders was 36.8% where response was defined as > or =20% reduction from baseline PANSS total score. The proportion of symptom worsening at 12 weeks was 7.4% (N=15) where symptom worsening was defined as > or =20% increase from baseline in PANSS total score or drop-out due to insufficient response or any 2 points change on any of 4 PANSS psychotic items (delusion, conceptual disorganization, hallucinatory behavior, suspiciousness/persecution) excluding changes in which the ratings remained at nonpsychotic levels (i.e >3). Significant improvement from baseline was also observed in the measure of parkinsonism assessed using Extrapyramidal Symptom Rating Scale (ESRS). In addition, overall, patients were satisfied with long-acting risperidone injection on a single item measure of satisfaction. When subgroup analysis was performed on the basis of previous antipsychotics before switching to long-acting risperidone, no statistically significant differences were detected between oral risperidone (N=139) and non-risperidone subgroup (N=65) on all measures of effectiveness and tolerability including baseline demographic and clinical characteristics, symptom improvements, proportion of symptom improvement or worsening and ESRS score changes. CONCLUSION: Our study results demonstrated maintained effectiveness and tolerability of long-acting risperidone microsphere and also could confirm successful switching from not only oral risperidone but also non-risperidone to long-acting risperidone injection.

Risperidone in Combination with Mood Stabilizers for Acute Mania: A Multicentre, Open Study / 신경정신의학

OBJECTIVE: The primary purpose of this study was a replication of the effectiveness and tolerability of risperidone in the treatment of patients with acute mania in very larger cohort in naturalistic treatment setting to extend the data on the effect and tolerability of risperidone in the treatment of patients with acute mania to Asian population. METHODS: A total of 909 patients with DSM-IV criteria of bipolar disorder current manic and hypomanic episode, entered this large, open, multicentre study. The Young Mania Rating Scale (YMRS), Clinical Global Impression (CGI) and Simpson-Angus Rating Scale (SARS) were measured at baseline and weeks 1, 3 and 6, for the assessment of effectiveness and extrapyramidal symptom (EPS). RESULTS: This study showed statistically significant reduction of scores on the YMRS and CGI-s (mean change=-23.5+/-11.8, p<0.0001;mean change=-2.7+/-1.5, p<0.0001, respectively) from the baseline to the endpoint (week 6). Number of patients with 50% reduction or more in the YMRS and CGI-s scores was 693 (77.8%) and 630 (70.7%) at endpoint, respectively. There were no statistically significant increments of scores on SARS. Risperidone was generally well tolerated. CONCLUSION: The present larger open study demonstrates that risperidone add-on therapy is effective and tolerable in treatment of bipolar disorder, replicating results in various controlled and uncontrolled studies from Western countries.

Other Physicians' Recognition and Satisfaction to the Psychiatric Consultation Service in a University Hospital / 신경정신의학

OBJECTIVE: The aim of this study were to investigate degree of satisfaction in referring physicians' psychiatric consultation services and their attitudes and opinions toward psychiatry, and the correlation between two them. METHOD: A total of 159 survey questionnaire were distributed to physicians in a University Hospital. The questionnaires contained the level of satisfaction in referring physicians' psychiatric consultation services and their attitudes and opinions toward psychiatry. 135 surveys were returned, representing 85% return rate. Statistical method used were Cronbach's alpha coefficient for testing reliability, factor analysis for testing validity, and t-test or ANOVA with SAS. RESULTS: Internal consistency reliability was tested by Cronbach's alpha. Cronbach's alpha was 0.8594 for total 23 items. Twenty-three items and seven factors were emerged and these contributed 66.8% of the variance in the total score. Factor I in the psychiatric consultation questionnaire was positively correlated with overall merits of the field of psychiatry in the attitude questionnaire, factor II in the psychiatric consultation questionnaire was positively correlated with possible abuses and social criticisms in the attitude questionnaire, factor III in the psychiatric consultation questionnaire was positively correlated with efficacy in the attitude questionnaire, factor V in the psychiatric consultation questionnaire was positively correlated with possible abuses and social criticisms in the attitude questionnaire, factor VI in the psychiatric consultation questionnaire was positively correlated with overall merits of the field of psychiatry in the attitude questionnaire. CONCLUSIONS: Our results supported the hypothesis that referring physicians' satisfaction to the psychiatric consultation was positively correlated with psychiatrists' attitude, and that physicians with more positive attitudes and those had more knowledge on psychiatry showed greater satisfaction in psychiatric consultation service than those without.

Revised Cognitive Impairment Diagnosing Instrument (CIDI): A Semi-Structured Interview Form for Assessment of Cognitive Functions / 신경정신의학

OBJECTIVES: This study was conducted in order to evaluate reliability and diagnostic validity of the CIDI. METHODS: 64 patients with DSM-IV dementia and 90 elderly patients with other mental disorders entered this study. Inter-subtest Pearson's correlations, corrected subtest-total correlations and Cronbach's alpha were computed for reliability while correlations of the total scores on CIDI with the performances on other scales relating to dementia, sensitivity and specificity, area under curve using the receiver operating characteristic curve, and group comparison were used for the assessment of validity. RESULTS: The CIDI's inter-subtest correlations ranged from 0.596 to 0.813, with a mean of 0.707. The corrected subtest-total correlations were between 0.759 and 0.890. Cronbach's alpha of the subtests was 0.941 and the Cronbach's alpha were between 0.928 and 0.948 when any subtest was deleted. In the demented subjects, the correlation coefficients of the total CIDI score with the performances on S-SDQ, IADL, BADL, BDRS, and MMSEK were around 0.5. Area under the receiver operating curve of CIDI was 0.933 with the standard error of 0.021(95% CI, 0.891-0.975). At the CIDI cutoff point of 65/66, sensitivity and specificity were 95.3% and 85.6%, respectively. The corresponding values of MMSEK were 0.930, 0.020 (95% CI, 0.891-0.969), 22/23, and 89.1% and 85.6%. The demented scored much poorer in all CIDI subtests than the nondemented mental patients, and the differences were highly significant. CONCLUSIONS: The CIDI was satisfactory regarding to reliabilities and diagnostic validities. The CIDI and MMSEK are thought to be reciprocal in assessment of cognitive functions: CIDI is preferable for clinical assessment of cognitive dysfunction and MMSEK for as a screening test.

Effects of Gender, Age, and Education on the Performances of the Korean Version of the Mini-Mental State Examination in an Elderly Rural Population / 신경정신의학

OBJECTIVES: To study of the effects of gender, age and education on the MMSEK performances in the elderly. METHOD: The MMSEK was administered to a total of 702 persons aged 65 or more in a rural area. The effects on the total and subtest MMSEK scores of the 3 independent variables were analyzed by Student t-test, Pearson's correlation, oneway analysis of variance, analysis of covariance, and stepwise multiple regression. RESULTS: The total and all subtest scores of MMSEK were found to be affected by age. All subtest, except memory registration and memory recall, scores were affected by education and sex. 39.6% of the variance of total MMSEK score could be accounted for by the 3 variables. CONCLUSIONS: 40% of the variance of the total MMSEK score could be accounted for by age, gender and education while the remaing 60% is assumed to be affected by other variables than age, sex, and education. Memory registration and memory recall seems to be resistant to sex and education effect, but sensitive to aging.

A 6-Year Follow-up of Cognitive Function in a Rural Elderly Population / 신경정신의학

OBJECTIVES: This study was conducted to delineate the long-term natural change of cognitive functions in aged community residents, using the Korean version of the mini-mental state examination (MMSEK) METHODS: The first MMSEK was administered to as the screening test for identification of dementia between January and December, 1990 in a total of 702 persons. They were residents of a Myun area, Pohang, Kyungpook Province and 65 or more as of December 31. 1990. The MMSEK was repeated from November, 1995 to June, 1996, using the Cognitive Impairment Diagnosing Instrument and was successful in 440. RESULTS: The 6-year mean(+/-SD) decline of the total MMSEK score was 1.52+/-3.45 and 6.42%. Of the subtests, memory registration showed no significant decline while comprehension/judgement improved significantly. The decline was most prominent in attention/calculation and memory recall, and then language, orientation in time and orientation in place in order. Change of the total score was not related to sex, education and the first total score. Decline of language function was more severe in the educated than in the noneducated-illiterate. Performances of all subtests declined significantly with aging and improvement of the comprehension/judgement was less prominent in the group aged 75 or more. Relations of the change with the first total score were inconsistent among the subtests. The stepwise multiple regression analysis revealed that age, the first total score and education were the variables significantly affecting the decline of MMSEK score. However, they could account for only 16.4% of the variance of decline of the total MMSEK score. CONCLUSIONS:Decline of the cognitive function was small during the 6-year period, and the change pattern was not homogenous among the subtests. Age, the first total MMSEK score and education were idenrified as significant, but not so important, factors accounting for the variance of the cognitive decline.

Diagnostic Predictive Values of Cognitive Function Tests

OBJECTIVE: The positive and negative predictive values are more important as the diagnostic validity than the sensitivity and specificity in the general population with a low prevalence rate of a disease. The present study is about the diagnostic predictive values of the Korean version of mini-mental state examination and Cognitive Impairment Diagnosing Instrument in an unselected community elderly group. METHOD: The positive and negative diagnostic values were calculated based on the Bayes theorem, using the sensitivity and specificity of the Korean version of mini-mental state examination and Cognitive Impairment Diagnosing Instrument and a previously reported prevalence rate. RESULTS: When the prevalence of dementia is 10.8% among elderly people living in a community, the positive predictive value, negative predictive value and combined error were estimated as being 56.7%, 99.0%, and 8.4%, respectively, at cutoff score of 23 of the Korean version of mini-mental state examination for diagnosing dementia. In the case of the Cognitive Impairment Diagnosing Instrument, they were 64.2%, 99.1% and 6.3%, respectively, at the point of 57 or less in an unselected community sample with the same prevalence. If the sensitivity and specificity are constant, the positive predictive values of the Korean version of mini-mental state examination and Cognitive Impairment Diagnosing Instrument incresed markedly with the rising prevalence while the negative predictive values and combined errors changed little. CONCLUSION: If a variety of diagnostic tests available are similar in the diagnostic sensitivity and specificity, a test with higher positive predictive value should be prefered because the negative predictive value and combined error are not significantly influenced by the prevalence. In this regard, the Cognitive Impairment Diagnosing Instrument may be superior to the Korean version of mini-mental state examination.

Diagnostic Predictive Values of Cognitive Function Tests

OBJECTIVE: The positive and negative predictive values are more important as the diagnostic validity than the sensitivity and specificity in the general population with a low prevalence rate of a disease. The present study is about the diagnostic predictive values of the Korean version of mini-mental state examination and Cognitive Impairment Diagnosing Instrument in an unselected community elderly group. METHOD: The positive and negative diagnostic values were calculated based on the Bayes theorem, using the sensitivity and specificity of the Korean version of mini-mental state examination and Cognitive Impairment Diagnosing Instrument and a previously reported prevalence rate. RESULTS: When the prevalence of dementia is 10.8% among elderly people living in a community, the positive predictive value, negative predictive value and combined error were estimated as being 56.7%, 99.0%, and 8.4%, respectively, at cutoff score of 23 of the Korean version of mini-mental state examination for diagnosing dementia. In the case of the Cognitive Impairment Diagnosing Instrument, they were 64.2%, 99.1% and 6.3%, respectively, at the point of 57 or less in an unselected community sample with the same prevalence. If the sensitivity and specificity are constant, the positive predictive values of the Korean version of mini-mental state examination and Cognitive Impairment Diagnosing Instrument incresed markedly with the rising prevalence while the negative predictive values and combined errors changed little. CONCLUSION: If a variety of diagnostic tests available are similar in the diagnostic sensitivity and specificity, a test with higher positive predictive value should be prefered because the negative predictive value and combined error are not significantly influenced by the prevalence. In this regard, the Cognitive Impairment Diagnosing Instrument may be superior to the Korean version of mini-mental state examination.