Mei-Chuan Chou

Application of AD8 Questionnaire to Screen Very Mild Dementia in Taiwanese

The AD8 questionnaire developed by Washington University in St Louis is a screening tool with 8 questions to reliably differentiate nondemented from demented individuals even at the very mild stage. We recruited 239 participants, including 114 cognitively normal, 73 very mild dementia, and 52 mild dementia to validate its application in Taiwanese. The cut-off value of AD8 was 2 in discriminating cognitively normal from demented individuals with the area under curve (AUC) = 0.961, sensitivity = 97.6%, specificity = 78.1%, positive likelihood ratio (PLR) = 4.5, and negative likelihood ratio (NLR) = 0.03. The cut-off value also was 2 in discriminating nondemented from very mild dementia with the AUC = 0.948, sensitivity = 95.9%, specificity = 78.1%, PLR = 4.4, and NLR = 0.05. The Chinese AD8 is effective in discriminating individuals with dementia, even at its mildest stages from those without dementia with properties identical to the original English version. The cAD8 is a quick dementia screening tool that can be applied across cultures.

Plasma concentration of donepezil to the therapeutic response of Alzheimer's disease in Taiwanese.

Donepezil has been approved for the treatment for mild-to-moderate Alzheimers disease (AD), but the therapeutic response rate varies from 20 to 60%. A higher oral dosage was suggested to have a better therapeutic response in reported results, but the plasma concentration of donepezil was not examined with respect to the therapeutic outcomes in those studies. Therefore, we analyzed the therapeutic responses, measured by neuropsychological assessments, among 70 newly diagnosed AD patients taking donepezil (5 mg daily) in relation to their plasma concentration of donepezil, apolipoprotein E genotype, and demographic characteristics. Our results have showed 60% of recruited AD patients improved in cognition, measured by Mini-Mental Status Examination (MMSE), and 57.1% in global status, by Clinical Dementia Rating Scale (CDR) sum of boxes (CDR-SB). In cognition, compared to the improving group, the clinically worsening group had a significantly higher donepezil concentration [p = 0.022, odds ratio (OR) = 1.024, 95% CI = 1.003-1.045] and higher initial MMSE score (p = 0.007, OR = 1.330, 95% CI = 1.080-1.639). In global status, initially higher CDR-SB (p = 0.028, OR = 2.318, 95% CI = 1.096-4.903) and initially higher MMSE (p = 0.036, OR = 1.201, 95% CI = 1.012-1.425), not donepezil concentration (p = 0.883), were significantly associated with clinical worsening. Our results have indicated that the dosage of donepezil should be reconsidered for AD patients, especially those clinically worsening in cognition.

Concentration of donepezil to the cognitive response in Alzheimer disease.

BackgroundDonepezil has been approved, and higher dosages are recommended for the treatment of Alzheimer disease (AD). However, a few studies have reported different cognitive responses in patients with AD treated with donepezil without measuring the concentration. MethodsWe evaluated the relationships between the therapeutic responses and plasma concentrations of donepezil in various cognitive domains using the Cognitive Ability Screening Instrument among 37 patients with newly diagnosed mild stage AD taking donepezil 5 mg/d. ResultsAmong the 9 cognitive domains in the Cognitive Ability Screening Instrument, the long-term memory domain had the highest improvement ratio (81.1%) compared with the other domains. An increased donepezil plasma concentration [mean (SD), 75.14 (32.16) ng/mL] was significantly associated with the improvement of long-term memory (P = 0.045; odds ratio, 0.959; 95% confidence interval, 0.920–0.999) after adjusting for age, sex, education, and apolipoprotein E genotype. ConclusionsAlthough there are some limitations in our study, these findings indicate that a higher concentration of donepezil improves long-term memory in patients with mild stage AD and imply the possible benefits in the advanced stage of AD for relatively preserved long-term memory.

Adjunct effect of music therapy on cognition in Alzheimer’s disease in Taiwan: a pilot study

Purpose Music therapy (MT) reviews have found beneficial effects on behaviors and social interaction in Alzheimer’s disease (AD) but inconsistent effects on cognition. The purpose of the study was to evaluate the adjunct effect of long-term and home-based MT in AD patients under pharmacological treatment. Patients and methods Mild AD cases (clinical dementia rating =0.5~1) were consecutively recruited and voluntarily separated into an MT group or control group (CG) for 6 months. Outcome assessments included Cognitive Abilities Screening Instrument (CASI), CASI-estimated mini-mental state examination, clinical dementia rating with sum of box scores, and neuropsychiatric inventory. The MT interventions were Mozart’s Sonata (KV 448) and Pachelbel’s Canon, listening with headphones for 30 minutes daily in the morning and before sleep, respectively. Results Forty-one cases (MT versus CG number =20 versus 21) were analyzed. Adjusted differences of CASI-estimated mini-mental state examination and CASI after 6 months in the MT group were slightly less decreased than the CG without statistical significance. In further analysis of cognitive domains of CASI, the adjusted difference of abstraction domain in the MT group was significantly better than the CG. Conclusion Although there were no apparent additional benefits of this MT on the global cognition and daily functioning in mild AD patients, it confirms the adjunct cognition effect on the abstraction. This MT contributes to the supplementary treatment of AD.

Plasma Homocysteine Levels and Major Depressive Disorders in Alzheimer Disease

BACKGROUND The main aim of this study was to examine the symptomatology of major depression in Alzheimer disease (AD) and its relationship with plasma homocysteine level. METHODS Eighty-three patients with AD were enrolled for clinical assessments and examination of fasting plasma homocysteine. Diagnosis of major depression was made, and the severity of the depression was assessed. RESULTS The moderate dementia patients presented with more common behavioral disturbances related to major depression than mild dementia patients. Major depression in patients with moderate AD was associated with higher plasma homocysteine levels. Furthermore, a high plasma homocysteine level was positively associated with behavioral disturbance among study participants with major depression. CONCLUSION More behavioral disturbance associated with major depression occurred as the dementia progressed. Patients with a higher level of plasma homocysteine presented with a higher behavioral disturbance symptomatology. This finding may account for the relationship between elevated homocysteine levels and depression only in patients with moderate AD.

Angiotensin-converting enzyme gene and plasma protein level in Alzheimer's disease in Taiwanese

BACKGROUND angiotensin-converting enzyme (ACE) gene insertion/deletion (indel) polymorphism is considered a biomarker for Alzheimers disease (AD). However, the associations of ACE gene and protein level to AD are undetermined among Taiwanese. METHODS this study investigated 257 Taiwanese cases with AD and 137 ethnically matched controls using ACE gene indel genotype association methods with logistic regression adjusted for other variables. Besides, 65 out of 257 AD patients, 11 with D/D genotype, 28 with I/I genotype and 26 with I/D genotype were recruited. Their plasma ACE protein levels were measured by enzyme-linked immuno-sorbent assay and compared for their corresponding ACE gene indel polymorphism. RESULTS patients with ACE-I/I homozygote were less likely to be associated with AD, compared with both I/D and D/D (OR: 0.601; 95% CI: 0.372-0.969; P = 0.037), or only I/D genotype (OR: 0.584; 95% CI: 0.349-0.976; P = 0.040). There were significantly different plasma ACE protein levels among these three different genotype groups (P = 0.023). The I/I genotype group had significantly lower ACE plasma levels [114.79 ± 31.32 ng/ml (mean ± SD)], compared with D/D (164.07 ± 86.36 ng/ml; P = 0.010), but not I/D (141.45 ± 51.50 ng/ml; P = 0.064). CONCLUSION ACE-I/I homozygote corresponds to lower plasma ACE protein level and it is independently but less likely to be associated with AD. These findings signal the importance of ACE indel polymorphisms to their corresponding protein levels and to AD.

Concentrations of rivastigmine and NAP 226-90 and the cognitive response in Taiwanese Alzheimer's disease patients.

The aim of this small pilot study was to evaluate the association between plasma concentrations of rivastigmine and its metabolite, NAP 226-90, and cognitive function in patients with Alzheimers disease (AD). Rivastigmine-treated AD patients, who had been maintained on a fixed regimen of twice daily rivastigmine (6 to 12 mg/d) for ≥6 months, were eligible for evaluation. The assessments included cognitive assessment screening instrument (CASI) and clinical dementia rating scale, conducted at baseline and at 6-month follow-up. The 9 subdomains of CASI at baseline and follow-up were analyzed in relation to the plasma concentrations of rivastigmine and NAP 226-90, as measured by capillary electrophoresis. Logistic regression was performed to adjust for age, gender, education level, apolipoprotein E ε4 genotype status, and baseline CASI score to investigate the association between plasma rivastigmine and NAP 226-90 concentrations and the cognitive response. The total sample consisted of 53 clinically diagnosed AD patients taking rivastigmine only at doses of 6 mg to 9 mg/d because of intolerability at 12 mg/d. Higher rivastigmine concentration was significantly associated with improved or preserved short-term memory and worsened abstraction/judgment (p < 0.05), but not with changes in other domains (p > 0.05). Higher NAP 226-90 concentration was significantly associated with worsened abstraction/judgment (p < 0.05), but not with changes in other domains. Higher plasma rivastigmine concentration was significantly associated with improved or preserved short-term memory but worsened abstraction/judgment. An optimal concentration of rivastigmine should be quantified for each patient because of differential cognitive responses.

Angiotensin-converting enzyme insertion/deletion polymorphism and the longitudinal progression of Alzheimer's disease

The angiotensin‐converting enzyme gene (ACE) insertion (I)/deletion (D) polymorphism is considered a biologically plausible gene for Alzheimers disease (AD) in cross‐sectional studies. The present study aimed to investigate the longitudinal effect of ACE I/D polymorphism on AD progression.

Clinical Compliance of Donepezil in Treating Alzheimer’s Disease in Taiwan

Background/Rationale: Adherence to cholinesterase inhibitor (ChEI) is associated with treatment effectiveness in the treatment of Alzheimer’s disease (AD). We investigated the clinical adherence to donepezil in Taiwan. Methods: This was a retrospective study. Patients treated with donepezil were recruited from Kaohsiung Medical University Hospital and Kaohsiung Municipal Ta-Tung Hospital from February 2004 to April 2013. We analyzed their treatment duration in months. Results: A total of 273 patients were included in our analysis. Sixty-seven patients withdrew from donepezil treatment with mean treatment duration of 28.0 ± 25.9 months. Better initial scores on the Mini-Mental Status Examination (P = .007), Cognitive Abilities Screening Instrument (P = .003), and the Clinical Dementia Rating Scale (CDR) Sum of Boxes (P = .011) were positively associated with clinical adherence. The clinical adherent rate was higher in the CDR-0.5 group than in the CDR-2.0 group with significant difference. Conclusion: Although there are some limitations in our study, these findings indicate that early intervention with ChEI in patients with AD should be emphasized and may lead to a better clinical adherence.

Factors affecting therapeutic response to Rivastigmine in Alzheimer's disease patients in Taiwan

Rivastigmine has been widely used in mild‐to‐moderate Alzheimers disease (AD), but the therapeutic response rate varies from 20 to 60%. A dose‐dependent effect has been suggested, but the plasma concentration of rivastigmine and its metabolite, NAP 226‐90, were not measured in previous studies. The influencing factors of therapeutic response are complicated and discordant in various studies among different ethnic groups. Hence, we analyzed the therapeutic responses of rivastigmine, measured by neuropsychological assessments, among 63 clinically diagnosed AD patients taking a daily dosage of 6–9 mg in relation to their plasma concentration of rivastigmine and NAP 226‐90, apolipoprotein E (APOE) genotype and demographic characteristics. Our reports revealed that 41.3% of recruited AD patients had improvement in cognition, measured by Mini‐Mental Status Examination (MMSE), and 63.5% in global status, by Clinical Dementia Rating Scale Sum of Boxes (CDR‐SB) score. In cognition, the clinically improving group had a significantly higher rivastigmine concentration [p = 0.049, odds ratio (OR) = 1.029, 95%CI = 1.000–1.058], lower initial MMSE score (p = 0.010, OR = 0.708, 95%CI = 0.546–0.920), and lower initial CDR‐SB score (p = 0.003, OR = 0.552, 95%CI = 0.372–0.817). The patients with APOE ε4 allele had worsening cognition (p = 0.037, OR = 3.870, 95%CI = 1.082–13.840). In global status, only higher education (p = 0.043, OR = 1.222, 95%CI = 1.007–1.484) was significantly associated with clinical improvement. In conclusion, high concentrations of rivastigmine may benefit cognitive function of AD patients, especially in APOE ε4 (−) carriers.