Li-Min Liou

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.

Cerebral White Matter Hyperintensities Predict Functional Stroke Outcome

Background: Growing evidence suggests that white matter hyperintensities (WMHs) are implicated in stroke recurrence and mortality, and their location can be a critical factor. This study evaluated the impact of periventricular WMHs (PVWMHs) and subcortical WMHs (SWMHs) on poststroke functional outcomes. Methods: Brain MRI was performed on 187 acute ischemic stroke patients (57.8% male; mean age = 64.3 years) recruited from the Kaohsiung Municipal Hsiao-Kang Hospital from February 2007 to January 2008. A Fazekas score ≥2 in the periventrcular or subcortical white matter was taken as presence of WMHs. Demographic data and risk factors for stroke were assessed. Functional stroke outcomes were evaluated 30 days after stroke using the Barthel Index (BI) and the modifiedRankin Scale (mRS). Results: WMHs were inversely linked to favorable functional outcome measured by mRS (p = 0.001) and BI (p = 0.003). Evaluating different locations, PVWMHs were associated with unfavorable functional outcomes (p = 0.002, mRS; p = 0.001, BI). SWMHs were related to mRS (p = 0.026) but not BI (p = 0.069). After controlling other stroke risk factors, infarct volumes and initial stroke severity, PVWMHs were a significant indicator for both mRS (OR = 2.76; 95% CI = 1.03–7.40) and BI (OR = 3.07; 95% CI = 1.13–8.40), but SWMHs were not. Conclusions: Unfavorable functional stroke outcome is associated with MRI WMHs. In terms of location, PVWMHs but not SWMHs are related to functional stroke outcome.

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.

Basal sympathetic predominance in periodic limb movements in sleep with obstructive sleep apnea

Because the impact of periodic limb movements in sleep (PLMS) is controversial, no consensus has been reached on the therapeutic strategy for PLMS in obstructive sleep apnea (OSA). To verify the hypothesis that PLMS is related to a negative impact on the cardiovascular system in OSA patients, this study investigated the basal autonomic regulation by heart rate variability (HRV) analysis. Sixty patients with mild‐to‐moderate OSA who underwent polysomnography (PSG) and completed sleep questionnaires were analysed retrospectively and divided into the PLMS group (n = 30) and the non‐PLMS group (n = 30). Epochs without any sleep events or continuous effects were evaluated using HRV analysis. No significant difference was observed in the demographic data, PSG parameters or sleep questionnaires between the PLMS and non‐PLMS groups, except for age. Patients in the PLMS group had significantly lower normalized high frequency (n‐HF), high frequency (HF), square root of the mean of the sum of the squares of difference between adjacent NN intervals (RMSSD) and standard deviation of all normal to normal intervals index (SDNN‐I), but had a higher normalized low frequency (n‐LF) and LF/HF ratio. There was no significant difference in the Epworth Sleepiness Scale, the Pittsburgh Sleep Quality Index, the Short‐Form 36 and the Hospital Anxiety and Depression Scale between the two groups. After adjustment for confounding variables, PLMS remained an independent predictor of n‐LF (β = 0.0901, P = 0.0081), LF/HF ratio (β = 0.5351, P = 0.0361), RMSSD (β = −20.1620, P = 0.0455) and n‐HF (β = −0.0886, P = 0.0134). In conclusion, PLMS is related independently to basal sympathetic predominance and has a potentially negative impact on the cardiovascular system of OSA patients.

Isolated aphasic status epilepticus as initial presentation of nonketotic hyperglycemia.

Diagnosis of aphasic status epilepticus is sometimes not easy because of its rarity and electroclinical dissociation. Although most cases are associated with organic brain lesions, nonketotic hyperglycemia (NKH)–related aphasic status epilepticus is rare, especially if it is isolated (without other clinical seizure activity). On the other hand, unlike other metabolic disorders, or hypoglycemia-related generalized seizures, focal motor seizure and epilepsia partialis continua can occur in 25% of NKH, with seizures being the initial manifestation in up to 50% of patients. However, the presentation of epileptic aphasia is rare in NKH patients. We report a rare case of NKH presenting initially as persistent and isolated aphasic status epilepticus. Brain magnetic resonance imaging did not reveal any focal lesion, but ictal electroencephalography (EEG) disclosed left frontotemporal continuous theta to delta waves, intermingled with epileptiform discharges. Correcting the hyperglycemia failed to improve the language disorder, and the seizure was controlled only by the addition of carbamazepine. Patients with NKH may initially present with isolated aphasic status epilepticus. Unlike stroke-related aphasia, accurate diagnosis is difficult if based solely on neurologic examination and brain neuroimaging. Use of EEG and blood sugar determination should be helpful in this special condition.

Timing of stroke onset determines discharge-functional status but not stroke severity: A hospital-based study

Circadian variation of the onset time of acute ischemic stroke has been well studied. However, little is mentioned about the circadian variation of discharge‐stroke severity and discharge‐functional status. This study evaluated the impact of onset time on discharge‐stroke severity and the functional status of acute ischemic stroke. Brain magnetic resonance imaging was performed on 274 acute ischemic stroke patients (66.42% male; mean age = 64.81 ± 12.80 years). All times of onset were assigned to 4‐hourly periods (six groups) starting from midnight. Stroke severity/functional status was evaluated on admission and discharge using the National Institute of Health Stroke Scale (NIHSS) score/modified Rankin Scale (mRS) and Barthel Index (BI), respectively. Using mRS, but not NIHSS score and BI, it was possible to differentiate the best and worst groups on discharge. Patients in group 2 (4 to <8 am) and group 6 (8 to <12 pm) had best and worst functional status, respectively. To control other stroke risk factors, multiple logistic regression analyses were conducted to examine the role of onset time in discharge mRS. Aside from age, onset time was a significant indicator in mRS, while gender, hypertension, diabetes mellitus, hyperlipidemia, atrial fibrillation, and current smoking were not. In conclusion, there is also circadian variation of discharge‐functional status in patients with acute ischemic stroke when assessed by mRS.

Improving the Potential of Neuroplasticity

A fundamental principle of neuronal plasticity is that synchronous or asynchronous activity in neurons can lead, respectively, to strengthening or weakening of shared synapses ([Hebb, 1949][1]). [Buch et al. (2011)][2] asked whether paired associative stimulation (PAS) of interconnected areas of the

Effects of metabolic syndrome, apolipoprotein E, and CYP46 on cognition among Taiwanese Chinese.

The combined effects of metabolic syndrome and the apolipoprotein E and CYP46 genotypes on the risk of cognitive decline has yet to be determined among Taiwanese Chinese. Two hundred and nine mentally healthy middle‐aged and older adults were assessed for metabolic syndrome, cognitive function using the Cognitive Abilities Screening Instrument, Mini‐Mental State Examination, ApoE, and CYP46 polymorphisms. There were no differences in cognitive performance, ApoE epsilon4 (ε4) carrier status, or CYP46 genotypes between participants with and those without metabolic syndrome. The ε4 carriers and participants with the AA allele of CYP46 had significantly lower mental manipulation score. Metabolic syndrome and ε4 had synergistic effects on cognitive decline. Therefore, the ε4 carriers and participants with the AA allele of CYP46 have decreased mental manipulation ability. The metabolic syndrome may play a role in subtle cognitive dysfunction in ε4 carriers among Taiwanese Chinese.

Predictive value of vertebral artery extracranial color-coded duplex sonography for ischemic stroke-related vertigo

Vertigo can be a major presentation of posterior circulation stroke and can be easily misdiagnosed because of its complicated presentation. We thus prospectively assessed the predictive value of vertebral artery extracranial color‐coded duplex sonography (ECCS) for the prediction of ischemic stroke‐related vertigo. The inclusion criteria were: (1) a sensation of whirling (vertigo); (2) intractable vertigo for more than 1 hour despite appropriate treatment; and (3) those who could complete cranial magnetic resonance imaging (MRI) and vertebral artery (V2 segment) ECCS studies. Eventually, 76 consecutive participants with vertigo were enrolled from Kaohsiung Municipal Hsiao‐Kang Hospital, Kaohsiung, Taiwan between August 2010 and August 2011. Demographic data, neurological symptoms, neurologic examinations, and V2 ECCS were assessed. We chose the parameters of peak systolic velocity (PSV), end diastolic velocity (EDV), PSV/EDV, mean velocity (MV), resistance index (RI), and pulsatility index (PI) to represent the hemodynamics. Values from both sides of V2 segments were averaged. We then calculated the average RI (aRI), average PI (aPI), average PSV (aPSV)/EDV, and average (aMV). Axial and coronal diffusion‐weighted MRI findings determined the existence of acute ischemic stroke. We grouped and analyzed participants in two ways (way I and way II analyses) based on the diffusion‐weighted MRI findings (to determine whether there was acute stroke) and neurological examinations. Using way I analysis, the “MRI (+)” group had significantly higher impedance (aRI, aPI, and aPSV/EDV ratio) and lower velocity (aPSV, aEDV, and aMV(PSV + EDV/2)), compared to the “MRI (–)” group. The cutoff value/sensitivity/specificity of aPSV, aEDV, aMV, aPI, aRI, and aPSV/EDV between the MRI (+) and MRI (–) groups were 41.15/61.5/66.0 (p = 0.0101), 14.55/69.2/72.0 (p = 0.0003), 29.10/92.1/38.0 (p = 0.0013), 1.07/76.9/64.0 (p = 0.0066), 0.62/76.9/64.0 (p = 0.0076), and 2.69/80.8/66.0 (p = 0.0068), respectively. Using way II analysis, lower aEDV and aMV, and higher aRI, aPI, and aPSV/EDV ratio could determine the “MRI (+) without focal signs” group. The cutoff value/sensitivity/specificity of aEDV, aMV, aPI, aRI, and aPSV/EDV between the MRI (+) without focal signs and MRI (–) groups were 9.10/71.4/96.0 (p = 0.0005), 15.65/57.1/96.0 (p = 0.0124), 1.10/100/70.0 (p = 0.0002), 0.64/100/70.0 (p = 0.0023), and 2.80/100/70.0 (p = 0.0017), respectively. In conclusion, using demographic data and clinical symptoms, it was difficult to determine the patients with ischemic stroke‐related vertigo. Although neurological examinations still have diagnostic value, the high impedance and low velocity pattern of V2 ECCS can be an add‐on method for the screening of acute ischemic stroke‐related vertigo, even for those without focal neurological signs.

Effect of cholesterol and CYP46 polymorphism on cognitive event‐related potentials

The integrated effect of the cholesterol and CYP46 genotypes on the risk of cognitive decline needs to be determined. Using the Cognitive Abilities Screening Instrument (CASI), 145 mentally healthy middle-aged and older adults were recruited to investigate the influence of cholesterol and CYP46 genotypes on cognitive event-related potentials (ERPs). The subjects with a high low-density lipoprotein cholesterol (LDL-C) level displayed significantly lower amplitude ERPs, although the CASI scores showed no difference. There was no association between the CYP46 genotypes, CASI scores, cholesterol levels, and measures of ERPs. No interaction between LDL-C level and CYP46 genotypes was noted. The LDL-C level is an independent predictor of low P300 amplitude. Prevention and treatment of high cholesterol may be of potential benefit in reducing cognitive impairment.