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.

Effects of Galantamine Treatment on Attention, Activities of Daily Living, and Neuropsychiatric Symptoms between the Patients with Pure Alzheimer's Disease and Mixed Dementia

OBJECTIVES: The purpose of this study was to compare the efficacy of galantamine treatment, especially attention ability between patients with pure Alzheimer's disease (AD) and Mixed dementia (MD) during a 24-week trial. METHODS: A total of 40 patients were recruited for this 24-week study. The effect of galantamine on attention was measured using Seoul Computerized NeuroCognitive Function Test (SCNT) and frontal functions test of Seoul Neuropsychological Screening Battery (SNSB). Patients'activities of daily living using the Seoul-Activities of Daily Living (S-ADL) and the Seoul-Instrumental Activities of Daily Living (S-IADL) ; behavioral symptoms using the Korean version Neuropsychiatric Inventory (K-NPI) were measured at baseline and 24-week. RESULTS: 17 pure AD patients and 23 MD patients were analyzed in this study. Attention as measured by SCNT was not significantly different from baseline after 24 weeks of treatment in both groups. There was no significant difference between two groups in mean change from baseline in the SCNT, S-ADL, S-IADL and K-NPI scores at 24-week. CONCLUSION: Galantamine showed a therapeutic effect on cognition, activities of daily living, neuropsychiatric symptoms in pure AD and MD. Furthermore, Galantamine may specifically help to maintain attention and it may have positive effects on other cognitive and functional abilities.

Comparative Assessment of Clinical Efficacy between the Naive and the Switching Group to Donepezil: 12 Months Prospective Study

OBJECTIVES: The purpose of this study was to compare the efficacy between switching patients with Alzheimer's disease (AD) from galantamine or rivastigmine to donepezil because they were not responding adequately, and naive patients with AD who initiated therapy with donepezil. METHODS: A total of 108 patients were recruited for this 52-week study. The effect of donepezil on cognitive function was measured using Alzheimer's Disease Assessment Scale-cognitive subscale-preliminary Korean version (ADAS-cog-K). Patients' activities of daily living using Seoul-Activities of Daily Living (S-ADL) and the Seoul-Instrumental Activities of Daily Living (S-IADL);behavioral symptoms using the Korean version Neuropsychiatric Inventory (K-NPI) were measured at baseline, 13-weeks, 26-weeks, 39-weeks and 52-weeks. We defined the responsive patients to donepezil at those who showed a cognitive improvement or no change during the first six-month clinical trial. RESULTS: 86 naive patients and 22 switching patients were enrolled in the study. 74 patients completed the study and 34 discontinued their treatment before week 52. There was no significant difference between two patient groups in demographic data, baseline characteristics and dementia severity except duration of illness. The total ADAS-cog-K scores were not significantly different from baseline after 52 weeks of treatment in both groups. Both groups demonstrated deterioration of S-ADL and S-IADL at 52 weeks. The NPI scores did not significantly change in both groups. Based on the operational criteria, 61.6% of the naive group and 54.5% of the switching group were responders to donepezil. CONCLUSION: The switching group had similar levels of efficacy with the naive group who initiated therapy with donepezil. These results suggest that patients not responding adequately to rivastigmine or galantamine may improve or stabilize after switching to donepezil and prior medication does not effect donepezil's efficacy.

Comparative Assessment of Clinical Efficacy after 12-Month Clinical Trial of Donepezil between the Patients with Pure Alzheimer's Disease and Mixed Dementia

OBJECTIVES: The purpose of this study was to compare the efficacy of donepezil treatment between patients with pure Alzheimer's disease (AD) and Mixed dementia (MD) during a 12-month trial. METHODS: A total of 139 patients were recruited for this 52-week study. The effect of donepezil on cognitive function was measured using Alzheimer's Disease Assessment Scale-cognitive subscale-preliminary Korean version (ADAS-cog-K). Patients' activities of daily living using the Seoul-Instrumental Activities of Daily Living (S-IADL) and Seoul-Activities of Daily Living (S-ADL);behavioral symptoms using the Korean version Neuropsychiatric Inventory (K-NPI) were measured at baseline, 13-weeks, 26-weeks, 39-weeks and 52-weeks. We defined the responsive patients to donepezil at those who showed a cognitive improvement or no change during the first six-month clinical trial. RESULTS: 84 pure AD patients and 34 MD patients were available for intent-to-treat (ITT) last observation carried forward (LOCF) analysis. There was no significant difference between two groups in mean change from baseline in the total ADAS-cog-k, S-ADL, S-IADL and K-NPI scores at 52-week. Based on the operational criteria, 60.7% of pure AD patients and 58.8% of MD patients were responders to donepezil. CONCLUSION: MD patients had similar levels of efficacy with pure AD patients and donepezil was well tolerated in both groups. These results suggest that donepezil is an effective and well-tolerated treatment for MD patients as well as for pure AD patients.

Comparative Assessment of Clinical Efficacy after 12-Month Clinical Trial of Donepezil between the Patients with Pure Alzheimer's Disease and Mixed Dementia

OBJECTIVES: The purpose of this study was to compare the efficacy of donepezil treatment between patients with pure Alzheimer's disease (AD) and Mixed dementia (MD) during a 12-month trial. METHODS: A total of 139 patients were recruited for this 52-week study. The effect of donepezil on cognitive function was measured using Alzheimer's Disease Assessment Scale-cognitive subscale-preliminary Korean version (ADAS-cog-K). Patients' activities of daily living using the Seoul-Instrumental Activities of Daily Living (S-IADL) and Seoul-Activities of Daily Living (S-ADL);behavioral symptoms using the Korean version Neuropsychiatric Inventory (K-NPI) were measured at baseline, 13-weeks, 26-weeks, 39-weeks and 52-weeks. We defined the responsive patients to donepezil at those who showed a cognitive improvement or no change during the first six-month clinical trial. RESULTS: 84 pure AD patients and 34 MD patients were available for intent-to-treat (ITT) last observation carried forward (LOCF) analysis. There was no significant difference between two groups in mean change from baseline in the total ADAS-cog-k, S-ADL, S-IADL and K-NPI scores at 52-week. Based on the operational criteria, 60.7% of pure AD patients and 58.8% of MD patients were responders to donepezil. CONCLUSION: MD patients had similar levels of efficacy with pure AD patients and donepezil was well tolerated in both groups. These results suggest that donepezil is an effective and well-tolerated treatment for MD patients as well as for pure AD patients.

Behavioral and Psychological Symptoms according to Severity in Patients with Alzheimer's Disease

OBJECTIVES: Our study investigated the behavioral and psychological symptoms of dementia (BPSD) in Alzheimer's disease (AD) patients with three groups (mild, moderate, severe) and prevalence of BPSD with the severity of AD. METHOD: In a study group of 338 patients with AD (mild:184, moderate:99, severe:55), information on gender, age, education was collected. The severity of dementia was measured by the Korean version of mini-mental status examination (K-MMSE) and Clinical dementia rating (CDR). The Korean version of Neruopsychiatric Inventory (K-NPI) was administered to all patients. RESULTS: Depression/dysphoria, apathy/indifference, irritability/lability, anxiety were frequent in the mild AD group. Apathy/indifference, Depression/dysphoria, agitation/aggression, delusion were frequent in the moderate AD group. Apathy/indifference, agitation/aggression, aberrant motor behavior, nighttime behavior, anxiety were frequent in the severe AD group. CONCLUSION: These observations suggest that delusion was a more dominant symptom in moderate AD group and the prevalence of depression declined in severe AD group.

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.

Neuropsychiatric Symptoms in Patients with Amnestic Mild Cognitive Impairment / 신경정신의학

OBJECTIVES : To define the neuropsychiatric features of amnestic-type Mild Cognitive Impairment (aMCI) and compare them with those of mild Alzheimer's disease (AD). METHODS : The study participants included 353 aMCI and 500 mild AD patients. The Neuropsychiatric Inventory (NPI) was used to assess the neuropsychiatric symptoms in two groups. RESULTS : 65.4% of aMCI and 85.4% of mild AD patients exhibited neuropsychiatric symptoms. The most common symptoms in the aMCI group were depression (33.7%), irritability (29.5%), sleep/ night-time behavior (23.2%), apathy (21.5%), and anxiety (21.2). The most common features in the mild AD group were depression (52.4%), apathy (52%), irritability (41.6%), and anxiety (41%). There were significant differences between the aMCI and mild AD groups in 11 NPI symptoms except sleep/night-time behavior. CONCLUSION : A high prevalence of neuropsychiatric symptoms were associated with aMCI, especially mood disturbances and apathy. In contrast, psychotic symptoms were rare. The neuropsychiatric symptoms observed in aMCI were similar to those of mild AD.

Neuropsychiatric Symptoms in Patients with Amnestic Mild Cognitive Impairment / 신경정신의학

OBJECTIVES : To define the neuropsychiatric features of amnestic-type Mild Cognitive Impairment (aMCI) and compare them with those of mild Alzheimer's disease (AD). METHODS : The study participants included 353 aMCI and 500 mild AD patients. The Neuropsychiatric Inventory (NPI) was used to assess the neuropsychiatric symptoms in two groups. RESULTS : 65.4% of aMCI and 85.4% of mild AD patients exhibited neuropsychiatric symptoms. The most common symptoms in the aMCI group were depression (33.7%), irritability (29.5%), sleep/ night-time behavior (23.2%), apathy (21.5%), and anxiety (21.2). The most common features in the mild AD group were depression (52.4%), apathy (52%), irritability (41.6%), and anxiety (41%). There were significant differences between the aMCI and mild AD groups in 11 NPI symptoms except sleep/night-time behavior. CONCLUSION : A high prevalence of neuropsychiatric symptoms were associated with aMCI, especially mood disturbances and apathy. In contrast, psychotic symptoms were rare. The neuropsychiatric symptoms observed in aMCI were similar to those of mild AD.

Clinical Utility of the Short Form of the Samsung Dementia Questionnaire (S-SDQ) in Mild Cognitive Impairment (MCI) / 신경정신의학

OBJECTIVES: Clinical utility of the Short Form of the Samsung Dementia Questionnaire (S-SDQ) as a screening instrument for Mild Cognitive Impairment (MCI). METHODS: Three groups (n=27, Subjective Memory Impairment (SMI); n=41 MCI; n=79, Early Alzheimer's Disease(AD)) recruited from memory clinic were administered a battery of neuropsychological tests including S-SDQ and Korean version-Mini Mental State Examination (K-MMSE). RESULTS: S-SDQ, unlike the K-MMSE, had no association with the age and education of the subjects. Scores of S-SDQ was found to correlate (r=-.496) with scores of K-MMSE. Result of Receiver Operating Characteristic (ROC) analysis revealed that S-SDQ discriminated between the SMI and the MCI groups. CONCLUSION: S-SDQ may be a solution to the problem of contamination by education and age which affect traditional cognitive screening instruments like K-MMSE, and it may be a useful tool for screening MCI.

Clinical Efficacy and Safety of Memantine in Patients with Moderate to Severe Dementia / 대한정신약물학회지

OBJECTIVE: This study examined the efficacy and safety of memantine-an uncompetitive N-methyl-D-aspartate (NMDA) receptor antagonist-in the treatment of moderate-to-severe dementia. METHODS: Forty-four patients with moderate-to-severe dementia received 20 mg of memantine daily for 24 weeks. The primary efficacy variable was measured by the Korean version of Severe Impairment Battery(K-SIB), and the secondary efficacy variables were measured using the Seoul-Activites of Daily Living(S-ADL) and Neuropsychiatric Inventory-Questionnaire(NPI-Q). Neuropsychological assessments were administrated at baseline, 12 weeks, and 24 weeks. Safety parameters were monitored. RESULTS: Of 44 patients recruited, 30 completed the study and 14 dropped out. Memantine-treated patients showed a therapeutic benefit in all efficacy variables ; the K-SIB, S-ADL, and NPI-Q total scores were not significantly different from baseline either at the endpoint(in the analysis of intention-to-treat, with the last observation carried forward, ITT-LOCF) or at week 24(in the analysis of observed cases, OC). The response rates, when "response" was defined as improved or unchanged in the K-SIB or the S-ADL scores, were 43.3 and 50%, respectively(in the analysis of OC). The responders showed significant improvement in the cognitive subdomain of memory function, praxis, visuospatial ability, and orienting to name. Memantine was shown to be tolerable and safe. CONCLUSIONS: Memantine treatment reduced or delayed clinical deterioration in cognition, function, and behavior in patients with moderate-to-severe dementia.

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.

The Study of Factors Related to Care Burden of Caregivers in Patients with Dementia / 신경정신의학

OBJECTIVES: The purpose of this study was to examine the determinants of care burden of caregivers in patients with dementia. METHODS: 128 dementia patients and patients' caregivers participated in this study. Care burden using the BI ; cognition using the K-MMSE ; dementia severity using the CDR ; activities of daily living using the S-ADL and the S-IADL ; behaviour problems using NPI were measured. RESULTS: The results showed that care burden was related significantly with the K-MMSE, the CDR, the S-ADL, the SIADL and the NPI total score. Of the behavior problems, agitation/aggression, anxiety, disinhibition, irritability, and aberrant behavior correlated positively with care burden of caregivers. Regression analysis indicated that agitation/aggression, anxiety, the CDR contributed to care burden. CONCLUSION: Agitation/aggression, anxiety and dementia severity contributed to care burden of caregivers. The identified determinants of care burden and the stress of caregivers suggest areas of therapeutic intervention to reduce caregiver's burden so that the institutionalization can be delayed.