Efficacy of Galantamine on Cognition in Mild-to-Moderate Alzheimer's Dementia after Failure to Respond to Donepezil.

OBJECTIVE: This study compares the efficacy of the cholinesterase inhibitor (ChEI) galantamine on cognition in patients with mild-to-moderate Alzheimer's dementia (AD) who were either naïve to ChEI drugs or who had failed a trial of the ChEI donepezil. METHODS: Outpatients with AD were sequentially referred for screening and enrollment. Current outpatients who had taken donepezil for at least 6 months without demonstrated efficacy on cognition were switched to galantamine (switched group). New outpatients with no ChEI prescription history were classified as the naïve group and were given galantamine. The primary outcome measures for the between-group comparison were response rate on cognition at 26 and 52 weeks (categorical) and change on the Korean version of the Alzheimer's Disease Assessment Scale-cognitive subscale (dimensional). Secondary cognitive outcomes were measured using the subset of frontal executive function and the Korean Mini-Mental State Examination. RESULTS: Seventy outpatients were enrolled and 66 were analyzed by Intent-to-treat (ITT). There were 42 cases in the naïve group and 24 in the switched group. Response rates did not differ at 26 weeks (71.4% naïve vs. 58.3% switched; p=0.277) or at 52 weeks (59.5% naïve vs. 41.6% switched; p=0.162). No significant differences were observed in the pattern of change over the 52 weeks on the primary and secondary cognitive scales. CONCLUSION: As the efficacy of galantamine on cognition was not inferior in the switched group compared to that in the naïve group, switching ChEI drugs is clinically feasible for non-responding patients with mild-to-moderate AD.

Overexpression of Cell Cycle Proteins of Peripheral Lymphocytes in Patients with Alzheimer's Disease.

OBJECTIVE: Biological markers for Alzheimer's disease (AD) will help clinicians make objective diagnoses early during the course of dementia. Previous studies have suggested that cell cycle dysregulation begins earlier than the onset of clinical manifestations in AD. METHODS: We examined the lymphocyte expression of cell cycle proteins in AD patients, dementia controls (DC), and normal controls (NC). One-hundred seventeen subjects (36 AD, 31 DC, and 50 NC) were recruited. The cell cycle proteins CDK2, CDK4, CDK6, cyclin B, and cyclin D were measured in peripheral lymphocytes. Cell cycle protein expression in the three groups was compared after adjusting for age and sex. RESULTS: The levels of cell cycle proteins CDK2, CDK4, CDK6, cyclin B, and cyclin D were significantly higher in AD patients than in the NC subjects. The DC group manifested intermediate levels of cell cycle proteins compared with the AD patients and the NC subjects. The present study indicates that cell cycle proteins are upregulated in the peripheral lymphocytes of AD patients. CONCLUSION: Cell cycle dysregulation in peripheral lymphocytes may present a promising starting point for identifying peripheral biomarkers of AD.

Cognitive subdomain responses to galantamine in Alzheimer's disease.

We investigated the effects of galantamine on cognitive subdomains in Alzheimer's disease (AD). Sixty-six patients with mild-to-moderate AD received open-label galantamine for 52 weeks. Cognitive function was measured using the Korean version of the Alzheimer's Disease Assessment Scale-cognitive subscale (ADAS-cog-K). Response to galantamine was defined as "improvement or no deterioration" on the total scores of the ADAS-cog-K at 26 weeks. In the overall intent-to-treat sample, we found less cognitive decline during 26 and 52 weeks than the expected untreated course as predicted by Stern's equation. The operationally defined response rate at 26 weeks was 66.7%. The responders differed significantly from the nonresponders only in the memory and language domains but not in the domains of praxis or frontal/executive function or in secondary outcome measures of neuropsychiatric symptoms and activities of daily living. The subdomain analysis revealed an effect of galantamine on preservation of memory that was not apparent in the overall analysis. Failure to achieve responder status by 26 weeks was associated with no further possibility of response.

Neuropsychiatric symptoms in korean patients with Alzheimer's disease: exploratory factor analysis and confirmatory factor analysis of the neuropsychiatric inventory.

BACKGROUND/AIMS: We designed this study to examine subsyndromes in Korean patients with Alzheimer's disease (AD) using exploratory factor analysis (EFA) and confirmatory factor analysis (CFA). METHODS: Initial participants were 778 AD patients recruited from the Clinical Research Center for Dementia of South Korea and assessed via the Korean Neuropsychiatric Inventory. Those with > or =1 neuropsychiatric symptom were randomly divided into groups. Principal axis factoring with oblimin rotation was used to analyze group 1 inventory results, and maximum likelihood estimation extraction with Bollen-Stine bootstrapping was used for group 2. RESULTS: The results of the EFA showed the presence of 4 subsyndromes: hyperactivity, affect, psychosis and apathy/vegetative symptom. The CFA results indicated this model was the best-fitting model for explaining these subsyndromes. CONCLUSION: Our model showed the best fit and identified 4 subsyndromes. This study might contribute to a clearer understanding of the neuropsychiatric symptoms in AD.

Impairment of instrumental activities of daily living in patients with mild cognitive impairment.

OBJECTIVE: THIS STUDY WAS CONDUCTED TO EXAMINE THE FOLLOWING: whether patients with mild cognitive impairment (MCI) show impairments in instrumental activities of daily living (IADL) as compared to controls; to identify the functional sub-domains of instrumental activities of daily living (IADL) that are affected in MCI and, finally, to identify the Seoul-Instrumental Activities of Daily Living (S-IADL) scale cut-off score that best differentiated between MCI and controls. METHODS: This study was carried out at the geropsychiatry clinic, university hospital. The study participants included 66 patients with MCI and 61 normal elderly. The S-IADL and Seoul-Activities of Daily Living (S-ADL) scales were administered to the main caregivers of all participants in order to assess everyday functioning. RESULTS: The total S-IADL score was significantly higher in the patients with MCI [mean (SD) score=4.47 (2.06)] than in the controls [mean (SD) score=1.44 (1.65)] (p<0.001). The patients with MCI performed significantly worse on IADLs, such as the ability to use the telephone, prepare meals, take medication, manage belongings, keep appointments, talk about recent events, and perform leisure activities/hobbies (p<0.05). The S-IADL scale discriminated well between patients with MCI and controls (Area Under Curve=87%). CONCLUSION: The patients with MCI showed impairments in the ability to perform complex ADL in comparison to healthy controls. IADLs related to memory and frontal/executive functioning were particularly affected in MCI.

Reliability and validity of a short form of the Severe Impairment Battery in Korean Alzheimer's disease patients.

The objective of this study was to evaluate the reliability and validity of a short form of the Severe Impairment Battery (SIB) for a Korean population. Eighty-four Alzheimer's disease patients with Clinical Dementia Rating (CDR) stages 2 (n = 32) or 3 (n = 52) and scores of less than 15 on the Korean version-Mini Mental State Examination (K-MMSE) participated in this study. Seventeen of the patients were men and 67 were women, and the mean age was 75 (SD = 10.4). Cronbach's coefficient alpha of the shortened SIB (SIB-S) was 0.93, and the item-total correlation was significant. Test-retest correlation for the total SIB-S score and subscale scores was significant, with the exception of the 'orienting to name' subscale. Construct validity was confirmed by evaluating the correlation between the SIB-S and the SIB, K-MMSE, CDR, and S-ADL; Spearman correlation coefficients were 0.96, 0.88, -0.67, and -0.63, respectively, which were found to be significant. The difference in the total SIB-S score and its subscale scores between the CDR 2 and CDR 3 groups was significant, except for the 'orienting to name' subscale. More severely demented patients also showed a wide range of the SIB-S score. Finally, the diagnostic accuracy of the SIB-S was high (AUC = 89.5%) in the differentiation of the CDR 2 and 3 patients. The sensitivity and specificity of the SIB-S were 91% and 80%, respectively, when the cut-off score was 32.5. Our results indicate that the SIB-S is a reliable and valid instrument for evaluating patients with severe dementia in the Korean population.

Reliability and validity of the severe impairment battery (SIB) in Korean dementia patients.

This study was conducted to examine the reliability, validity and clinical utility of the Severe Impairment Battery (SIB) for a Korean population. 69 dementia patients with Clinical Dementia Rating (CDR) stages 2 or 3 were participated in this study. The SIB, Korean version-Mini Mental State Examination (K-MMSE), CDR, and Seoul-Activities of Daily Living (S-ADL) were administered. The validity of the SIB was confirmed by evaluating the correlation coefficients between the SIB and K-MMSE, CDR, S-ADL, which were found to be significant. Cronbach's alpha for the total SIB score and each subscale score showed high significance, and the item-total correlation for each subscale was also acceptable. The test-retest correlation for the total SIB score and subscale scores were significant, except for the praxis and orienting to name. The total SIB score and subscale scores were examined according to CDR. The results suggest that the SIB can differentiate the poor performances of severely impaired dementia patients. On the basis of the receiver operating characteristic (ROC), it can be concluded that the SIB is able to accurately discriminate between CDR 2 and 3 patients. The results of this study suggest that the SIB is a reliable and valid instrument for evaluating severe dementia patients in Korean population.