Chiou-Lian Lai

The role of event-related potentials in cognitive decline in Alzheimer’s disease

OBJECTIVES Early diagnosis and monitoring of disease progression have become vital in clinical practice as disease modifying treatments for Alzheimers disease (AD) become available. This one-year prospective study aimed to clarify the usefulness of event-related potentials (ERPs) in cognitive decline and elucidate their cognitive significance in AD. METHODS Using the Cognitive Abilities Screening Instrument (CASI) and ERPs, probable AD patients, mild cognitive impairment (MCI) patients, and normal controls were recruited. RESULTS The AD and MCI patients had significantly decreased cognitive function and manifested a delay of P300 latency. The P300 latencies demonstrated significantly more prolongation than their baseline values in probable AD and MCI patients, although their CASI scores showed no statistically significant decline. Whereas N100, P200, and N200 components did not reach statistical differences between groups either in the baseline or follow-up assessments and did not show significant change on follow-up. CONCLUSION The combination of neuropsychological tests and P300 measurements proved useful in improving reliability and increasing sensitivity to early cognitive decline or disease progression in AD patients. SIGNIFICANCE The P300 latency may reflect cognitive decline more sensitively than neuropsychological tests in the longitudinal follow-up of AD patients.

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.

Cognitive and Motor Components of Response Speed in the Stroop Test in Parkinson's Disease Patients

This study assessed the performance of patients with Parkinsons disease (PD) in the Stroop test. Twenty‐seven patients with PD (17 men, 10 women; mean age, 63.3 ± 10.5 years) and 27 age‐matched controls (14 men, 13 women; mean age, 63.5 ± 9.2 years) were administered the color‐naming, word‐reading, and incongruent color‐word‐naming tasks in the Stroop test. Compared with the normal control group, the PD group had slower speeds for all three tasks and greater Stroop interference, indicating a response inhibition deficit in PD patients. Further analysis indicated that slowness during color naming might be due to motor slowness, rather than a central cognitive processing problem in color discrimination. In conclusion, the performance of the PD group on the three tasks of the Stroop test suggests that the PD patients were deficient in motor responses and cognitive inhibitory abilities.

Eradication of Helicobacter pylori Is Associated with the Progression of Dementia: A Population-Based Study.

Objective. To evaluate the effect of eradication of Helicobacter pylori (H. pylori) on the progression of dementia in Alzheimers disease (AD) patients with peptic ulcer. Methods. Participants with the diagnosis of AD and peptic ulcer were recruited between 2001 and 2008. We examined the association between eradication of H. pylori and the progression of AD using the multiple regression models. Medication shift from Donepezil, Rivastgmine, and Galantamine to Mematine is defined as progression of dementia according to the insurance of National Health Insurance (NHI) under expert review. Results. Among the 30142 AD patients with peptic ulcers, the ratio of medication shift in AD patients with peptic ulcers is 79.95%. There were significant lower incidence comorbidities (diabetes mellitus, hypertension, cerebrovascular disease, coronary artery disease, congestive heart failure and hyperlipidemia) in patients with H. pylori eradication as compared with no H. pylori eradication. Eradication of H. pylori was associated with a decreased risk of AD progression (odds ratio [OR] 0.35 [0.23–0.52]) as compared with no H. pylori eradication, which was not modified by comorbidities. Conclusions. Eradication of H. pylori was associated with a decreased progression of dementia as compared to no eradication of H. pylori in AD patients with peptic ulcers.

Apolipoprotein E polymorphism and behavioral and psychological symptoms of dementia in patients with Alzheimer disease.

The aims of this study were to identify subsyndromes of behavioral and psychological symptoms of dementia (BPSD) in Alzheimer disease (AD), and to investigate whether the apolipoprotein E (ApoE) gene confers a risk of distinct BPSD subsyndromes. BPSD of 96 patients with AD were assessed using the Neuropsychiatric Inventory. Factor analysis with principal component analysis and varimax rotation was used to construct the BPSD subsyndromes. ApoE genotypes were determined using the TaqMan technology. The results showed that the 5 subsyndromes can be determined, including: agitation/aggression-delusion, euphoria-disinhibition, depression-apathy, hallucination-nighttime behavior, and appetite. ApoE &egr;4 carriers had higher factor scores in the agitation/aggression-delusion subsyndrome. We demonstrated that ApoE &egr;4 confers a higher risk for the subsyndrome of agitation/aggression delusion in AD.

Reappraisal of heart rate variability in acute ischemic stroke.

Cardiac autonomic dysfunction is a common complication after acute ischemic stroke (IS). Prior investigators have emphasized that infarction of brain stem or hemispheres with insular involvement is related to this dysfunction and may predict poor clinical outcome. From the viewpoint of stroke physicians, however, all stroke patients, particularly large‐artery atherosclerosis (LAA) should be monitored for possible cardiac complications after acute IS. This study aimed to investigate cardiac autonomic impaction in patients with acute IS and to make the comparison between LAA and small‐vessel occlusion (SVO) subtypes. Of the 126 acute IS patients prospectively enrolled in this study, 32 had LAA, 56 had SVO, and 38 had undetermined etiology according to the Trial of Org 10172 in Acute Stroke Treatment criteria. Cardiac autonomic function of all patients was assessed by measuring heart rate variability (HRV). The low‐ and high‐frequency components of HRV in all stroke patients were significantly lower than those of control subjects after comparing multivariable models, including additional adjustments for age, gender, and all risk factors. There were no significant differences on HRV between LAA and SVO although post hoc comparisons showed that stroke patients of SVO had increased sympathetic modulation and reduced vagal activity. In conclusion, in acute IS patients, both LAA and SVO are predisposed to have cardiac autonomic dysfunction, manifesting as abnormalities in HRV, whether in hemispheric or brain stem lesions. Stroke patients of SVO are at higher risks of cardiac abnormalities, which might suggest an early cardiac dysfunction because of long‐term hypertension. The HF component of HRV thought to be for vagal control might be a cardinal marker for predicting cardiac autonomic dysfunction after acute IS. Short‐term HRV spectral analysis is a convenient approach for stroke clinicians to assess autonomic function in acute stroke. Long‐term follow‐up for HRV and clinical outcome relative to LAA and SVO stroke subtypes is warranted, particularly when an abnormal HRV is found at admission.

Association of apolipoprotein E polymorphism with ischemic stroke subtypes in Taiwan.

The aim of this study was to clarify whether the apolipoprotein E gene (APOE) is related to ischemic stroke subtypes in Taiwans Chinese population. Using the classification of Cerebrovascular Diseases III, 143 patients with lacunar infarction, 114 patients with atherothrombotic infarction, and 112 healthy controls were enrolled. APOE genotype was determined using polymerase chain reaction. Regarding the distribution of APOE genotypes, the frequency of ɛ3/ɛ4 genotypes in lacunar patients was significantly different from that in control subjects, by logistic regression, using ɛ3/ɛ3 as a reference group. There was no significant difference between atherothrombotic patients and the control group in the distribution of APOE genotypes or alleles. The present finding suggests that there is a probable association between ɛ3/ɛ4 genotype and lacunar infarcts, but not atherothrombotic infarcts. This indicates that genetic factors may play a role, at least partially, in lacunar infarction in Taiwans Chinese population.

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.

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.

Relationship between ischemic stroke location and autonomic cardiac function

Autonomic cardiac dysfunction is a common complication after acute ischemic stroke (IS). We recruited 75 patients with acute IS with measurements of autonomic cardiac function, including heart rate variability (HRV) and associated parameters, and compared them with 81 controls. Of the 75 patients, 28 had right hemispheric infarctions (RH), 29 had left hemispheric infarctions (LH), and 18 had brainstem infarctions (BS). A comparison of HRV in all patients with stroke and in control subjects showed significant differences between IS subgroups and controls in low frequency (LF), high frequency (HF), normalized LF, normalized HF, and LF/HF ranges. A post-hoc comparison identified significant differences between patients with IS with BS infarctions and the control group in LF, HF, and LF/HF ranges. BS infarction may cause a much greater increase in sympathetic modulation and reduced vagal activity compared to RH or LH infarction. Our findings provide evidence that acute IS causes significant damage to the cardiovascular autonomic system, manifesting as abnormalities of HRV. BS stroke might correlate with a significant reduction in parasympathetic and an increase in sympathetic influence on HRV.