Ae Young Lee

Increased brachial–ankle pulse wave velocity is independently associated with risk of cerebral ischemic small vessel disease in elderly hypertensive patients

OBJECTIVE Increased arterial stiffness is an independent predictor of cardiovascular diseases in hypertensive patients. Hypertension and aging can cause similar damage to small vessel walls. The objective of this study was to determine relationship between arterial stiffness measured by brachial-ankle pulse wave velocity (baPWV) and the risk of cerebral small vessel disease (SVD) in elderly people with hypertension. METHODS We studied 196 elderly subjects with hypertension (> or =50 years of age) who had neither large vessel stroke nor cardiac embolism. These patients were divided into three groups based on the results of brain MRI: (1) those with first-ever small vessel stroke; (2) those with asymptomatic subcortical ischemia; and (3) a control group with hypertension. RESULTS The baPWV was significantly increased in the patients with first-ever small vessel stroke or asymptomatic subcortical infarction when compared to the control group, after adjusting for systolic blood pressure (SBP), pulse pressure (PP), and hs-CRP (p=0.005). Among subjects with SVD on MRI, the number of lacunar infarcts (LIs)> or =5 was significantly related to a higher baPWV (p=0.02). The relationship between the severity of periventricular white matter hyperintensities (PWMH) and the degree of baPWV became insignificant after adjustment for age. CONCLUSION Increased baPWV was significantly associated with the risk of SVD in elderly persons with hypertension. Therefore, the measurement of baPWV could be used to predict SVD.

Periodic alternating nystagmus in isolated nodular infarction

Periodic alternating nystagmus (PAN) is characterized by periodic reversal of horizontal jerky nystagmus with a null period of several seconds. Damage to the uvulonodulus or to their connections with the brainstem vestibular nuclei has been suggested as a mechanism of PAN.1,2 However, PAN has rarely been reported in circumscribed cerebellar lesion.3 We report a patient with isolated nodular infarction who developed PAN without fixation in association with perverted head-shaking nystagmus (HSN) and loss of tilt suppression of the postrotatory nystagmus. This is the first report of PAN in circumscribed cerebellar infarction, and provides further evidence that PAN occurs due to dysfunction of cerebellar nodulus. A 69-year-old man with a history of hypertension developed acute vertigo with nausea/vomiting and postural imbalance. On examination, we observed spontaneous horizontal nystagmus in the primary position which reversed its direction with a cycle of approximately 2 minutes and a transition period of several seconds by using video Frenzel goggles (SLMED, Seoul, Korea) (see the video on the Neurology Web site at www.neurology.org). The …

Relationship between changes of body mass index (BMI) and cognitive decline in Parkinson's disease (PD).

Decreased BMI has been reported that it may be associated with cognitive decline in the elderly. Weight loss is common in patients with PD. However, studies comparing cognitive changes according to BMI changes in PD have not been done yet. We performed this study to know a relationship between BMI changes and the rate of cognitive decline in PD. PD patients were recruited retrospectively. The patients (n=104) were divided into two groups according to BMI changes during initial 6 months of follow-up: decreased (n=52) vs. stable BMI groups (n=52). Cognitive functions were repeated until 36 months of follow-up using the Korean version of the Mini-Mental State Examination (K-MMSE) and the modified Mini-Mental State (3MS) test. We calculated the rate of cognitive decline (K-MMSE and 3MS score changes/month) and compared it between the two groups. The decreased BMI group showed lower level of cognitive function than that of stable BMI group, especially at the 36th month of follow-up (p<0.05). In addition, the rate of cognitive decline was also significantly faster in the decreased BMI group, particularly at the 36th month of follow-up (p<0.05). This study suggests that decreased BMI during initial 6 months of follow-up in PD might be a useful indicator for future risk of dementia and let clinicians predict faster rate of cognitive decline in patients with PD.

Measurement of Precuneal and Hippocampal Volumes Using Magnetic Resonance Volumetry in Alzheimer's Disease

Background and Purpose Alzheimers disease (AD) is associated with structural alterations in the medial temporal lobe (MTL) and functional alterations in the posterior cortical region, especially in the early stages. However, it is unclear what mechanisms underlie these regional discrepancies or whether the posterior cortical hypometabolism reflects disconnection from the MTL lesion or is the result of local pathology. The precuneus, an area of the posteromedial cortex that is involved in the early stages of AD, has recently received a great deal of attention in functional neuroimaging studies. To assess the relationship between the precuneus and hippocampus in AD, we investigated the volumes of these two areas using a magnetic resonance volumetric method. Methods Twenty-three subjects with AD and 14 healthy age-matched controls underwent T1-weighted three-dimensional volumetric brain magnetic resonance imaging. Volumetric measurements were performed in the precuneus and hippocampus. Results Compared to controls, AD patients exhibited a significant reduction in total precuneal volume, which was more prominent on the right side, and significant bilateral reductions in hippocampal volume. No correlation was found between the total volumes of the precuneus and hippocampus in the AD group. Conclusions These results suggest that volumetric measurements of both the precuneus and hippocampus are useful radiological indices for the diagnosis of AD. Furthermore, the lack of correlation is attributable to local pathology rather than being a secondary consequence of MTL pathology.

Longitudinal changes in clock drawing test (CDT) performance according to dementia subtypes and severity

UNLABELLED The CDT requires a patient to draw the face of a clock, insert all the numbers and set the hands for a specified time. This task engages a number of cognitive abilities including verbal understanding, memory, spatially coded knowledge, planning, concentration and visuoconstructive skills. Although CDT has been regarded as a simple and useful screening tool in dementia, little is known about the longitudinal changes in CDT performance and error types, according to dementia subtypes and their severity. MATERIALS AND METHODS Two hundred thirty-five consecutive patients with dementia (Alzheimer disease = AD, n=94, Parkinsons disease with dementia (PDD), n = 119, Vascular dementia = VaD, n = 22) were recruited from the memory clinic at Chungnam University hospital from January 2005 to July 2009. The Korean version of the mini-mental state examination (MMSE-K) and CDT were performed by all participants every 6 months. Scoring of the CDT performance was in accordance with the method of Mano and Wu. Error types of CDT were classified as follows: stimulus-bound response (SBR), conceptual deficit (CD), spatial and/or planning deficit (SPD) and perseveration error (PE). We divided patients into 3 groups by their initial MMSE-K score (severe, MMSE-K ≤ 17; moderate, 18 ≤ MMSE-K < 24; mild, 24 ≤ MMSE-K). Comparisons of CDT scores and error types in the three dementia subtypes and three cognitive groups were conducted. RESULTS Longitudinal changes on CDT and MMSE-K scores were not different between the three dementia subtypes. From the analysis of CDT error type, the most common error type was SPD in patients with mild to moderate dementia. In contrast, CD error was the most frequent in severe dementia group. The order of error frequency in all subjects from baseline to the last follow-up was as follows: SPD, CD, SBR and PE except CD was the most frequent error type in AD patients after 18 months from baseline. CONCLUSION Longitudinal analysis of error on CDT may reflect different characteristics of cognitive deterioration according to dementia subtypes and dementia stages.

Treatment of Alzheimer's Disease with Repetitive Transcranial Magnetic Stimulation Combined with Cognitive Training: A Prospective, Randomized, Double-Blind, Placebo-Controlled Study

Background and Purpose Repetitive transcranial magnetic stimulation (rTMS) has been examined as a potential treatment for many neurological disorders. High-frequency rTMS in particular improves cognitive functions such as verbal fluency and memory. This study explored the effect of rTMS combined with cognitive training (rTMS-COG) on patients with Alzheimers disease (AD). Methods A prospective, randomized, double-blind, placebo-controlled study was performed with 27 AD patients (18 and 8 in the treatment and sham groups, respectively, and 1 drop-out). The participants were categorized into mild [Mini-Mental State Examination (MMSE) score=21-26] and moderate (MMSE score=18-20) AD groups. The rTMS protocols were configured for six cortical areas (both dorsolateral prefrontal and parietal somatosensory associated cortices and Brocas and Wernickes areas; 10 Hz, 90-110% intensity, and 5 days/week for 6 weeks). Neuropsychological assessments were performed using the AD Assessment Scale-cognitive subscale (ADAS-cog), Clinical Global Impression of Change (CGIC), and MMSE before, immediately after, and 6 weeks after the end of rTMS-COG treatment. Results Data from 26 AD patients were analyzed in this study. There was no significant interactive effect of time between the groups. The ADAS-cog score in the treatment group was significantly improved compared to the sham group (4.28 and 5.39 in the treatment group vs. 1.75 and 2.88 in the sham group at immediately and 6 weeks after treatment, respectively). The MMSE and CGIC scores were also improved in the treatment group. Based on subgroup analysis, the effect of rTMS-COG was superior for the mild group compared to the total patients, especially in the domains of memory and language. Conclusions The present results suggest that rTMS-COG represents a useful adjuvant therapy with cholinesterase inhibitors, particularly during the mild stage of AD. The effect of rTMS-COG was remarkable in the memory and language domains, which are severely affected by AD.

Effect of cardiac function on cognition and brain structural changes in dementia.

Background and Purpose Cardiovascular risk factors are considered to also be risk factors for dementia. Recent studies have shown that the prevalence of cognitive dysfunction is high in patients with cardiac diseases. However, few studies have investigated the influence of cardiac function on cognition and brain structural changes in dementia. The aims of this study were to determine the relationship between cardiac and cognitive function, and to characterize any structural changes in the brain that could be caused by cardiac function in patients with dementia. Methods Dementia patients (n=93) were recruited prospectively with checking for the presence of vascular risk factors such as hypertension. Cognitive function was measured by the Mini-Mental State Examination, modified Mini-Mental State test, and Korean version of the Dementia Rating Scale. Brain magnetic resonance imaging was conducted to evaluate the cerebral white-matter changes (WMC), ventricular dilation, and cortical and hippocampal atrophy. Cardiac function was evaluated using two-dimensional echocardiography. We divided the patients into two groups according to the presence (+) or absence (-) of WMC. Results In the entire cohort, the size of the left atrium (LA) was positively correlated with the degree of WMC, irrespective of age (p<0.05). The LA was larger in the WMC (+) group (n=42) than in the WMC (-) group. General cognitive function was significantly lower in the WMC (+) group than in the WMC (-) group. Subjects with an enlarged LA tended to exhibit lower cognitive function and more-severe cerebral WMC. Conclusions Cardiac dysfunction represented by LA enlargement could be related to cognitive decline and WMC of the brain resulting from impairment of the cerebral hemodynamic process in dementia.

Relationship between brachial-ankle pulse wave velocity and cognitive function in an elderly community-dwelling population with metabolic syndrome

Arterial stiffness (AS) and metabolic syndrome (MS) may correlate with poor cognitive function in elderly people. However, few studies have evaluated this relationship in a healthy, community-dwelling elderly population. Our aim was to evaluate a relationship between the AS measured by pulse wave velocity (PWV) and cognitive function and to know whether the relationship is influenced by the presence of MS. Our study population was community-dwelling healthy people in Geumsan province, Republic of Korea. A total of 370 participants without a history of cerebrovascular disease were evaluated with the Korean version of the mini-mental state examination (K-MMSE) and have measured the brachial-ankle PWV (baPWV). Correlation between baPWV and cognitive status and effect of MS were measured. Negative correlation between PWV and cognitive function was found in the older subjects (> or = 60 years of age) with MS (r=-0.38; p<0.05). In the receiver operating characteristic (ROC) curve, the cut-off score was 1800.8 cm/s with 67% sensitivity and 78% specificity. Aging (older than 60 years) and the presence of MS may affect synergistically cognitive decline in the elderly population. The baPWV can be a useful predictor for cognitive decline in elderly healthy community-dwelling population with MS.

A novel PYGM mutation in a Korean patient with McArdle disease: The role of nonsense-mediated mRNA decay

We have identified a compound heterozygous mutation of PYGM in a Korean patient with McArdle disease, which is composed of a novel single codon deletion (p.779delE) and a common nonsense mutation (p.R50X). Our study also showed an evidence of nonsense-mediated mRNA decay (NMD) caused by p.R50X mutation, supporting the importance of RNA processing defects in the molecular pathology of McArdle disease.

Perverted Head Impulse Test in Cerebellar Ataxia

In the bedside head impulse test (HIT), the clinician identifies the catch-up saccades after head rotation as an indirect sign of vestibulo-ocular reflex (VOR) deficit [1]. Positive HIT can be observed in central vestibulopathies, in addition to peripheral vestibulopathies [2–4]. Recent reports proposed that a positive HIT in these patients with preserved caloric response is most likely due to cerebellar flocculus dysfunction, considering the findings of earlier studies related to high-frequency VOR [2–4]. Also, the dysconjugate upward eye deflection during yaw head impulse was also observed in patients with cerebellar disease [5, 6]. Here, we first documented video clips of upward trajectories during horizontal head impulses in a patient with cerebellar ataxia, i.e., perverted HIT, which could be another feature of positive HIT in central vestibulopathies.