G1/S Cell Cycle Checkpoint Defect in Lymphocytes from Patients with Alzheimer's Disease

OBJECTIVE: We compared the cell responsiveness of activated lymphocytes to rapamycin, which blocks the G1/S transition, between patients with Alzheimer's disease (AD) and normal controls to assess the early phase control defect in cell cycle. METHODS: Blood samples of 26 patients with AD and 28 normal controls were collected to separate peripheral lymphocytes. We measured the proportion of each cell cycle phase in activated lymphocytes using flow cytometry and evaluated the responsiveness of these lymphocytes to rapamycin. RESULTS: The patients with AD were older than the normal controls (AD 74.03+/-7.90 yr vs. control 68.28+/-6.21 yr, p=0.004). The proportion of G1 phase cells in the AD group was significantly lower than that in the control group (70.29+/-6.32% vs. 76.03+/-9.05%, p=0.01), and the proportion of S phase cells in the AD group was higher than that in control group (12.45+/-6.09% vs. 6.03+/-5.11%, p=0.001). Activated lymphocytes in patients with AD were not arrested in the G1 phase and they progressed to the late phase of the cell cycle despite rapamycin treatment, in contrast to those of normal subjects. CONCLUSION: The patients with AD probably have a control defect of early phase cell cycle in peripheral lymphocytes that may be associated with the underlying pathology of neuronal death.

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.