Yuan-Han Yang

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.

Eligibility for Recombinant Tissue Plasminogen Activator in Acute Ischemic Stroke

Background: The eligibility for recombinant tissue plasminogen activator (rtPA) is rare. We analyze the reasons for exclusion from rtPA among patients who were admitted to our hospital within 3 h. Methods: A strict protocol for hyperacute stroke was set in a university teaching hospital. Consecutive patients activating the protocol from June 2004 to October 2005 were prospectively registered and entered into a computerized database. The patients were excluded from rtPA according to the modified exclusion criteria from the National Institute of Neurological Disorders and Stroke rtPA trial. Results: Of the 182 patients activating the protocol, only 11 (6.04%) received intravenous rtPA and 4 (2.2%) IA thrombolysis. Patients were excluded for multiple reasons, and the main reasons for exclusion were minor or improving stroke (46.15%), hypertension (35.16%), insufficient time to complete studies or onset beyond 3 h after reconfirmation (24.17%) and intracranial hemorrhage (15.93%). Of 167 excluded patients, 72 (43.11%) were excluded by a single criterion, 53 (31.73%) by 2 criteria and 29 (17.36%) by 3 criteria. The mean time from hospital arrival to presentation to a neurologist was 9.24 ± 15.11 min (n = 164, median = 8.00, mode = 10, range = 0–65). The mean time from hospital arrival to computed tomography (CT) was 21.67 ± 23.95 min (n = 167, median = 20.00, mode = 10, range = 4–68). Conclusion: An intrahospital stroke code was implemented to minimize intrahospital delay. However, only 11 patients received intravenous rtPA and 4 IA thrombolysis at our hospital from June 2004 to October 2005. The result brings into question the neurologist’s conservative interpretation of the criteria and the necessity to clearly define some criteria. Furthermore an intrahospital stroke code should also be implemented for inpatients to maximize the eligibility for rtPA.

METACOHORTS for the study of vascular disease and its contribution to cognitive decline and neurodegeneration. An initiative of the Joint Programme for Neurodegenerative Disease research

Dementia is a global problem and major target for health care providers. Although up to 45% of cases are primarily or partly due to cerebrovascular disease, little is known of these mechanisms or treatments because most dementia research still focuses on pure Alzheimers disease. An improved understanding of the vascular contributions to neurodegeneration and dementia, particularly by small vessel disease, is hampered by imprecise data, including the incidence and prevalence of symptomatic and clinically “silent” cerebrovascular disease, long‐term outcomes (cognitive, stroke, or functional), and risk factors. New large collaborative studies with long follow‐up are expensive and time consuming, yet substantial data to advance the field are available. In an initiative funded by the Joint Programme for Neurodegenerative Disease Research, 55 international experts surveyed and assessed available data, starting with European cohorts, to promote data sharing to advance understanding of how vascular disease affects brain structure and function, optimize methods for cerebrovascular disease in neurodegeneration research, and focus future research on gaps in knowledge. Here, we summarize the results and recommendations from this initiative. We identified data from over 90 studies, including over 660,000 participants, many being additional to neurodegeneration data initiatives. The enthusiastic response means that cohorts from North America, Australasia, and the Asia Pacific Region are included, creating a truly global, collaborative, data sharing platform, linked to major national dementia initiatives. Furthermore, the revised World Health Organization International Classification of Diseases version 11 should facilitate recognition of vascular‐related brain damage by creating one category for all cerebrovascular disease presentations and thus accelerate identification of targets for dementia prevention.

Pre-hospital and In-hospital Delays After Onset of Acute Ischemic Stroke—A Hospital-based Study in Southern Taiwan

The biggest hurdle for early hospital presentation is the narrow therapeutic window after stroke. The aims of our study were to investigate the time lags and the factors causing pre‐hospital and emergency department (ED) delay during acute ischemic stroke attack. Between June 2004 and October 2005, we prospectively studied 129 acute ischemic stroke patients who presented to the ED of the study hospital within 4 hours after symptom onset. Chi‐square testing for trend, uni‐variate and multiple logistic regression analyses was performed to evaluate the factors influencing delays in the ED presentation of acute ischemic stroke patients. The median time from symptom onset to ED arrival was 71 (mean ± SD, 82.7 ± 57.7) minutes. The median times from ED arrival to neurologic consultation, computed tomography scan, electrocardiogram, and laboratory data completion were 10 (11.3±9.9) minutes, 17 (9.6±11.3) minutes, 14 (23.3±55) minutes, and 39 (44.4±24.5) minutes, respectively. Univariate and multiple logistic regression models revealed that age < 65 years, illiteracy and awakening with symptoms were the most significant factors related to a delay in ED presentation. This study indicates that 2 hours of pre‐hospital delay is the cutoff point for thrombolytic therapy. Organization of a stroke team and standardized stroke pathways may help to shorten in‐hospital time consumption. Educational efforts should not only focus on the public, but also on the training of ED physicians and other medical personnel.

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.

The Informant AD8 is Superior to Participant AD8 in Detecting Cognitive Impairment in a Memory Clinic Setting

The informant AD8 has good discriminatory indices in detecting questionable dementia. However, studies on participant AD8 yielded inconsistent results. This study aims to investigate the discriminatory ability of the AD8 in detecting cognitive impairment at a memory clinic by comparing the informant AD8, participant AD8, Montreal Cognitive Assessment (MoCA), and Mini-Mental State Examination (MMSE). The AD8 was administered to 280 participant-informant dyads. The MoCA and MMSE were administered to all participants, who subsequently received a comprehensive clinical and neuropsychological assessment leading to a consensus diagnosis and a Clinical Dementia Rating (CDR). Area under the receiver operating characteristic curve (ROC) analysis was used to compare the discriminatory ability of AD8, MoCA, and MMSE. Participants were Chinese (83.6%) females (54.3%) with a mean age and education of 73.4 ± 8.6 years and 6.2 ± 5.6 years, respectively. The discriminant validity of the informant AD8 was significantly superior to the participant AD8 in detecting cognitive impairment (CDR ≥ 0.5) {Area Under Curve (AUC) [95% confidence interval (CI)]: 0.96 (0.93-0.98) versus 0.66 (0.58-0.74), p < 0.01}. Furthermore, the informant AD8 was equivalent to MoCA and MMSE in detecting cognitive impairment {AUC [95% CI]: MoCA [0.98 (0.96-0.99)]; MMSE [0.95 (0.93-0.98)]}. The informant AD8 (≥2) had very good sensitivity and specificity, while the participant AD8 (≥2) had suboptimal sensitivity and specificity in detecting cognitive impairment (sensitivity 0.93 versus 0.59; specificity 0.87 versus 0.65; 91.8% versus 60% correctly classified). The informant AD8 is superior to the participant AD8, and equivalent to the MMSE and MoCA in screening for cognitive impairment in memory clinic patients.

Registration of Alzheimer's disease in Taiwan: Patient and informant

Background: To obtain updated data of patients with Alzheimer’s disease (AD) and their informants in Taiwan with the aim of fostering and supporting collaborative research. Methods: In total, 691 patients with the diagnosis of AD were recruited at 6 sites in Taiwan. The Uniform Data Set (UDS; form A) was administrated. Results: The mean age of the patients with AD was 79.3 ± 7.7 years and the mean age of informants was 57.5 ± 13.7 years. In all, 69% of the informants lived with patients and 77% of patients lived with spouse, partner, or children; 11% had 1 sibling with dementia, 1.8% had 2 siblings with dementia, and 0.5% had 3 or more siblings with dementia. Conclusion: We have reported the updated status of AD in Taiwan through a UDS that will foster future collaboration among countries using UDS. The updated information of patients with AD and their informants will direct the future care of AD in Taiwan.

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.

Cilostazol as an add-on therapy for patients with Alzheimer’s disease in Taiwan: a case control study

BackgroundCombination therapy using acetylcholinesterase inhibitors (AChEIs) and cilostazol is of unknown efficacy for patients with Alzheimer’s disease (AD).MethodsWe explored the therapeutic responses by using a case–control study, which was conducted in Taiwan. We enrolled 30 participants with stable AD who were receiving cilostazol (50 mg) twice per day as an add-on therapy combined with AChEIs, and 30 participants as controls who were not receiving cilostazol as an add-on therapy. The therapeutic responses were measured using neuropsychological assessments and analyzed in relation to cilostazol use, apolipoprotein E genotype, and demographic characteristics. Mini-mental state examination (MMSE) and clinical dementia rating sum of boxes (CDR-SB) were administered at the outset of the study and 12 months later. Multiple logistic regression analysis was used to estimate the association between the therapeutic response and cilostazol use.ResultsFor the therapeutic indicator of cognition, Cilostazol use (adjusted odds ratio (aOR) = 0.17, 95% confidence interval (CI) = 0.03–0.80), initial CDR-SB score (aOR = 2.06, 95% CI = 1.31–3.72), and initial MMSE score (aOR = 1.41, 95% CI = 1.11–1.90), but not age, sex, education, or ApoE ε4 status, were significantly associated with poor therapeutic outcomes. For the therapeutic indicator of global status, no significant association was observed between the covariates and poor therapeutic outcomes.ConclusionsCilostazol may reduce the decline of cognitive function in stable AD patients when applied as an add-on therapy.

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.