The Effects of Galantamine Treatment on Attention and Its Relationship with Cognition and Activities of Daily Living in Patients with Mild to Moderate Alzheimer's Disease

BACKGROUND AND PURPOSE: The positive effects of galantamine on cognition and activities of daily living (ADL) in Alzheimer's disease (AD) are thought to be mediated via improvements in attention. The purpose of this study was to determine the effect of galantamine on attention in AD patients using a computerized attention test and to elucidate the relationship between improvements in attention and change in cognition and ADL. METHODS: In this multicenter, open-label, prospective study, patients with mild to moderate AD received galantamine and then submitted to computerized attention tests, the Alzheimer's Disease Assessment Scale-cognitive subscale, and instrumental ADL (IADL) at baseline, 4 weeks, and 12 weeks. The differences in reaction time on computerized tests were explored relative to the changes in cognition and IADL. RESULTS: After 12 weeks of taking the trial medication there was a significant reduction from baseline levels in the choice reaction time (baseline, 5,216+/-3,650 sec; 12 weeks, 4,139+/-2,920 sec; p<0.01) and the simple reaction time (baseline, 1,089+/-782 sec; 12 weeks, 908+/-606 sec; p<0.01). Correlation analyses of changes in choice or simple reaction times relative to cognition and ADL measures yielded no significant associations. The improvement in attention observed at 4 weeks of galantamine treatment was not associated with any significant changes in outcome measures at the end of trial. CONCLUSIONS: This study found no significant association between the improvement in attention after treatment with galantamine and changes in cognition and ADL in patients with mild to moderate AD, despite the significant improvement in attention over the course of the treatment.

The Prevalence and Severity of Neuropsychiatric Symptoms in Alzheimer's Disease and Subcortical Vascular Dementia : the CREDOS Study

OBJECTIVES: This study aimed to compare the prevalence and severity of clinically relevant neuropsychiatric symptoms between subjects with Alzheimer's disease (AD) and subcortical vascular dementia (SVD). METHODS: The CREDOS (Clinical Research for Dementia Of South Korea) is a multicenter longitudinal cohort study organized to evaluate the long-term outcome of dementia patients. Out of a total 3,080 subjects, we selected 1,392 AD subjects and 247 SVD subjects with mild to moderate levels of dementia. The Neuropsychiatric Inventory (NPI) and Clinical Dementia Rating Scale (CDR), and CDR sum of box scores were used for evaluation. RESULTS: After controlling for severity of dementia and duration of education, SVD subjects had relatively more symptoms of apathy compared to AD subjects (OR : 1.397, p=0.025). SVD subjects also had relatively higher NPI composite scores in the apathy domain compared to AD subjects, after controlling for severity of dementia, age and duration of education (F=7.88, p=0.01). Subjects with moderate levels of dementia had more frequent and severe neuropsychiatric symptoms compared to those with mild dementia. CONCLUSION: Symptoms of apathy were more prevalent and severe in subjects with SVD, compared to subjects with AD.

Identification of PSEN1 and APP Gene Mutations in Korean Patients with Early-Onset Alzheimer's Disease

Although mutations in three genes, amyloid precursor protein (APP), presenilin 1 (PSEN1), and presenilin 2 (PSEN2), have been identified as genetic causes of earlyonset Alzheimer s disease (EOAD), there has been a single report on a PSEN1 mutation in Koreans. In the present study, we performed a genetic analysis of six Korean patients with EOAD. Direct sequencing analysis of the APP, PSEN1 and PSEN2 genes revealed two different mutations of the PSEN1 gene (G206S and M233T) and one mutation of the APP gene (V715M) in three patients with age-atonset of 34, 35, and 42 yr, respectively. In addition, two patients with age-at-onset of 55 and 62 yr, respectively, were homozygous for APOE epsilon 4 allele. One woman had no genetic alterations. These findings suggest that PSEN1 and APP gene mutations may not be uncommon in Korean patients with EOAD and that genetic analysis should be provided to EOAD patients not only for the identification of their genetic causes but also for the appropriate genetic counseling.

Dipole Source Localization of Periodic Sharp Wave Complexes in Creutzfeldt-Jakob Disease

BACKGROUND: Patients with Creutzfeldt-Jakob disease (CJD) show periodic sharp wave complexes (PSWCs) on electroencephalography (EEG) during the course of their illness. However, the source location of PSWCs and the pathophysiological mechanism remains unclear. METHODS: Ten patients with sporadic CJD who showed typical PSWCs on EEG underwent brain magnetic resonance imaging (MRI) and positron emission tomography (PET, n=8) or single-photon emission computed tomography (SPECT, n=2) scans. A 30-second epoch from the EEG was selected for analysis. The recording was separated blindly using independent component analysis. The separate independent components were subjected to dipole source localization using a single dipole model. The source locations were compared with neuroimaging findings in each patient. RESULTS: Two to three independent components responsible for the PSWCs seen in CJD were identified. The EEG recording reconstructed from the selected independent components accounted for about 70% of the variance in the original recording. All but one patient had dipole sources localized in both cortical and subcortical areas. One patient had only subcortical dipole sources in both caudate nuclei. The cortical locations included the cingulate, insula, frontal, temporal, and occipital areas. The subcortical sources were located in the striate, thalamic, and subthalamic nuclei. All the dipole sources were localized within lesions seen as neuroimaging abnormalities. CONCLUSIONS: These results suggest that a subcortical mechanism, in addition to cortical structures, is involved in producing the generalized periodic discharges in CJD.

Urinary Incontinence in the Patients with Dementia / 대한비뇨기과학회지

No abstract available.

A Short form of the Samsung Dementia Questionnaire ( S-SDQ ): development and cross-validation

BACKGROUND: The Samsung Dementia Questionnaire (SDQ) has recently been developed for screening dementia. Objectives of this study are to develop a short form of SDQ (S-SDQ) and to cross-validate S-SDQ in a new sample. METHODS: Factorial analysis of SDQ items was used to develop the S-SDQ. The S-SDQ was administered to informants of 100 dementia patients (61 Alzheimer's disease, 39 vascular dementia) and to those of 100 hospital control subjects. Two groups were matched in terms of age and sex. The retest of S-SDQ was conducted in 75 informants to determine the reliability of tests and retests which were spanned average 23.9 days. RESULTS: The S-SDQ was not influenced by education, age or sex. S-SDQ scores negatively correlated with the K-MMSE (r=-0.84). The S-SDQ showed stepwise scaling with dementia severity. The area under the ROC curve for the S-SDQ was 0.974 (S.E.=0.084). With respect to a diagnosis of dementia, the SDQ (cut-off point 8) had a sensitivity of 94% and a specificity of 90%. The S-SDQ was found to have a high test-retest reliability (r=0.97). CONCLUSIONS: An abbreviated version of SDQ (S-SDQ) had high sensitivity, specificity and test-retest reliability which were comparable to those of original SDQ. Thus, the S-SDQ can be a useful, brief dementia screening questionnaire.

Two Cases of Palilalia

BACKGROUND: Palilalia is characterized mainly by compulsive repetitions of words and phrases, which are attenuated in loudness and increased in rate. Up to date, approximately 29 cases of palilalia secondary to various neurological insults were reported mostly as a single case study. To our knowledge, there has been no reported case of palilalia in Korea until now. In this report, we present two patients with palilalia. CASES: The first patient KH, a 52-year-old man, with vascular parkinsonism, exhibited the repetition after an episode of stroke in the bilateral basal ganglia area. The second patient SH, a 60-year-old man with idiopathic Parkinson's disease, also manifested the repetition of words and phrases. The speech performance of both patients varied with the type of speech tasks, for instance, propositional language as opposed to automatic language. COMMENT: Palilalia should be differentlly diagnosed from neurogenic stuttering, echolalia, or aphasic perseveration. A pathophysiological explanation of patient KH's palilalia would be an widespread extrapyramidal impairment that resulted in destruction of the inhibitory motor circuit which might lead to the abnormal, uncontrolled speech-related neuronal firing in the frontal lobe. On the other hand, patient SH's palilalic speech may result from hyperexcitation of downstream of dopaminergic system related to peak-dose dyskinesia.

Rapidly Progressive congnitive Deciline and Ataxic Gait

No abstract available.

functional MRI of Language Area

PURPOSE: To evaluate the usefulness of functional MR imaging(fMRI) for language mapping and determination of language lateralization. MATERIALS AND METHODS: Functional maps of the language area were obtained during word generation tasks and decision task in ten volunteers(7 right handed, 3 left-handed). MR examination were performed at 1.5T scanner with EPI BOLD technique. Each task consisted of three resting periods and two activation periods with each period of 30 seconds. Total acquisition time was 162sec. SPM program was used for the postprocessing of images. Statistical comparisons were performed by using t-statistics on a pixel-by-pixel basis after global normalization by ANCOVA. Activation areas were topographically analyzed(p<0.001) and activated pixels in each hemisphere were compared quantitatively by lateralization index. RESULTS: Significant activation signals were demonstrated in 9 of 10 volunteers. Activation signals were found in the premotor and motor cortices, the inferior frontal, inferior parietal, and mid-temporal lobes during stimulation tasks. In the right handed seven volunteers, activation of language areas was lateralized to the left side. Verb generation task produced stronger activation in the language areas and higher value of lateralization index than noun generation task or decision task. CONCLUSION: fMRI could be a useful non-invasive method for language mapping and determination of language dominance.

A Case of Alzheimer's Disease Manifesting as Posterior Cortical Atrophy

A subgroup of patients with progressive degenerative dementia that begins with higher visual dysfunction has been referred to as posterior cortical atrophy (PCA). A 55-year-old woman presented with progressive visual disturbance for 4 years, which was followed by geographical disorientation, impairment of writing and calculation, and memory distur-bance. Neuropsychological deficits were characterized by Balint syndrome, visuospatial dysfunction, prosopagnosia, Gerstmann syndrome and apraxia. Brain MRI showed mild diffuse atrophy. F18-FDG-PET disclosed bilateral occipi-totemporoparietal hypometabolism, more pronounced on the right. Biopsy from right temporal lobe revealed neu-ropathological findings consistent with Alzheimer's disease.

A Case of Alzheimer's Disease Manifesting as Posterior Cortical Atrophy

A subgroup of patients with progressive degenerative dementia that begins with higher visual dysfunction has been referred to as posterior cortical atrophy (PCA). A 55-year-old woman presented with progressive visual disturbance for 4 years, which was followed by geographical disorientation, impairment of writing and calculation, and memory distur-bance. Neuropsychological deficits were characterized by Balint syndrome, visuospatial dysfunction, prosopagnosia, Gerstmann syndrome and apraxia. Brain MRI showed mild diffuse atrophy. F18-FDG-PET disclosed bilateral occipi-totemporoparietal hypometabolism, more pronounced on the right. Biopsy from right temporal lobe revealed neu-ropathological findings consistent with Alzheimer's disease.

Usefulness of Apolipoprotein E4 and Distribution of Petechial Hemorrhages in Differentiating between Cerebral Amyloid Angiopathy and Hypertensive Intracerebral Hemorrhage

BACKGROUND AND OBJECTIVES: Cerebral amyloid angiopathy (CAA) accounts for a significant proportion of spontaneous lobar hemorrhages in the elderly population but hypertension is responsible for most cases of deep-seated hemorrhage. Reportedly petechial hemorrhages (PHs) can be associated with CAA or chronic hypertension. We determined the location of PHs and apolipoprotein E (APOE) genotype in intracerebral hemorrhage (ICH) patients and tried to correlate them with CAA associated or hypertensive ICH. METHODS: One hundred and sixty-two consecutive patients with primary ICH were evaluated clinically and by MRI. PHs were defined as small low-signal lesions (less than 1 cm) seen on T2-weighted or gradient-echo MR images. ICH and PHs were divided into lobar (cortical-corticosubcortical), deep (basal ganglia, thalamus, pons, or cerebellum), or mixed. APOE genotype was determined by polymerase chain reaction. All 162 patients were classified into 4 groups: 1) probable CAA (multiple lobar bleeds without other cause), 2) possible CAA (single lobar bleed), 3) probable hypertensive ICH (deep bleed), and 4) mixed lobar and deep hemorrhages. RESULTS: Among 162 patients, 31 belonged to the probable and possible CAA groups and 17 of them showed PHs (7 lobar, 4 deep, 6 mixed). One hundred and twenty-two patients were the hypertensive ICH group and 63 of them had PHs (2 lobar, 10 mixed, 51 deep). Lobar PHs were more frequently observed in the probable and possible CAA group than the hypertensive ICH group (22.6%: 1.6%, p < 0.01) while deep PHs were seen mainly in the hypertensive ICH group (41.8%: 12.9%, p < 0.01) and these tendencies are also observed in the group who had taken both T2-weighted and gradient-echo MR images (64 patients). The frequency of hypertension was significantly lower in the probable and possible CAA groups with lobar PHs than in the hypertensive ICH group with deep PHs (57.1%: 98 %, n = 7 & 51 respectively, p < 0.01). APOE ?4 frequency was: probable (freq. 0.25, n = 2), possible CAA (freq. 0.21, n = 7), hypertensive (freq. 0.056, n = 9), and mixed hemorrhages (freq. 0.071, n = 7). The frequency of APOE ?4 of probable and possible CAA group seems to be higher than that of normal control (freq. 0.19, n = 146). CONCLUSION: APOE ?4 and PHs in lobar areas may be associated with hemorrhages restricted to lobar regions while hypertension and PHs in deep areas, with hemorrhages restricted to deep regions.

Alzheimer's Disease: Report of two cases

Alzheimer's disease (AD) is the most common etiology of dementia, that has not been previously reported in Korea. We have experienced two cases of Alzheimer's disease, one occurred in a 53-year-old man with dementia and the other occurred in a 36-year-old woman with a family history of early onset dementia. A neocortical biopsy was done to rule out the cause of dementia and showed diffusely scattered numerous senile plaques and neurofibrillary tangles in cortex of both cases. Interestingly, GFAP, an immunohistochemical stain showed strong positivity in neuritic plaques and the surrounding fibrillary gathering.

Alzheimer's Disease: Report of two cases

Alzheimer's disease (AD) is the most common etiology of dementia, that has not been previously reported in Korea. We have experienced two cases of Alzheimer's disease, one occurred in a 53-year-old man with dementia and the other occurred in a 36-year-old woman with a family history of early onset dementia. A neocortical biopsy was done to rule out the cause of dementia and showed diffusely scattered numerous senile plaques and neurofibrillary tangles in cortex of both cases. Interestingly, GFAP, an immunohistochemical stain showed strong positivity in neuritic plaques and the surrounding fibrillary gathering.

Selective Neuronal Damage Produced by beta-fluoroethylacetate Intoxication in Rat Brain

Beta-fluoroethylacetate has been extensively used as the rodenticide in Korea. In some patients with acute poisoning, beta-fluoroethylacetate caused cerebellar dysfunction as a single and persistent neurologic sequela after a period of an acute neurological disorder which is characterized by mental deterioration, seizures, and respiratory failure. But there has been no report of pathological findings to explain neurological deficit. We tried to verify the histologic changes of the central nervous systems in beta-fluoroethylacetate poisoned rats. Silver staining(Gallyas) was used to evaluate the histology. In acute intoxication experiment with LD50(7mg/Kg), beta-fluoroethylacetate elicited acute onset of consciousness deterioration, generalized tonic-clonic seizures and large amplitude tremulous activity involving whole body with full recovery after 24 hours. There was no discernible pathologic change in CNS in acutely poisoned rats. However, when poisoned with sublethal dose(5mg/Kg) daily for five days, a moderate degree of nerve cell degeneration was found selectively in dentate nucleus, Purkinie cell layer, vestibulo-cochlear nucleus and striatum. This change was not seen in hippocampus, cerebral cortex or cerebellar cortex. These findings were well correlated with the previous reports of selective pathology in human 5-FU intoxication cases. Our preliminary results suggest that beta-fluoroethylacetate, a kind of cellular metabolism inhibitor may induce selective neuropathology mainly involving cerebellar output pathway in rats.

Is Roussy-Levy Syndrome the same as Charcot-Marie-Tooth Disease?

We report data on 2 members of a family affected by a dominantly inherited disorder closely resembling Roussy-Levy syndrome(RLS) Electrophysiological findings showed a marked decrease of motor and sensory conduction velocities and mild neurogenic damage. Light and electron microscopy of sural nerve biopsy showed a hypertrophic neuropathy with diffuse onion-bulb formations and marked decrease of large size fibers. Teased fiber preparations revealed reduced internodal lengths and segmental demyelination. The hypothesis that RLS is not a disease entity but a hypertrophic-type of Charcot-Marie Tooth disease with essential tremor(HMSN type 1) is strongly supported.

Hereditary Optic Atrophy, Neural Deafness, and Peripheral Neuropathy

The triad of bilateral optic atrophy, hearing deficit, peripheral neuropathy is knoun to be a rare disorder. The authors experienced eight patients in three generations of the same family with this triad of deficits. The disorder developed since their childhood and the course was slowly progressive. Nerve conduction study suggested peripheral neuropathy and sural nerve biopsy was compatible with demyelinating neuropathy, as there were reduction of myelinated nerve fibers in number and focal onion-bulb formation. The mode of inheritance of the family seems to be autosomal dominant, with relatively high penetrance. In many respects, the disorder resembles the cases reported by Sylvester(1958) and Iwashita et al.(1970). But still we do not know the exact etiology of this disorder.

A Clinical Study on Chronic Carbon Disulfide(CS2) Intoxication

Carbon disulfide(CS2), a volatile solvent, has been widely used in the manufacture of the artificial silk because of its highly fat-soluble property. It has been accepted that CSz is mostly absorbed to the human beings by inhalation arld does harms mainly to the central and peripheral nervous systems and the cardiovascular system. But it is conkoversial whether the pathologic changes are due to the direct toxic effects of the CS2 or to the secondary effects of the CS2-induced arteriosclerosis. Recently the authors have observed the six patients of viscose-rayon worker with a longstanding exposure to the CS2 and obtained the results as follows:1. The ages of onset in the 6 subjects (5 males and one female) were ranged from @41 to 53 years(mean;47.1) and the duration of exposure from 11 to 18 years(mean;l4.5). 2. Three of them had no hypertension. 3. Neurologically they showed headache, dizziness, general malaise, gait difficulty, visual and memory disturbances, paresthesia of distal extremities, dementia, parkinsonian features, pseudobubar palsy, spastic gait, dysarthria, hyperreflexia, and reduced or absent ankle jerks. 4. Nerve conduction studies(N=4) revealed that three of them had polyneuropathy of axonal type.

Leptomeningeal Metastasis Presented before Primary cancer

Leptomeningeal metastasis(LM) usually occurs in patients with previous cancer. But rarely it can be the first manifestation of cancer. We analyzed primary tumors and early clinical findings in 12 patients in whom LM was the presenting sign of cancer. Primary tumors were lung cancer in 5 cases, stomach cancer 1, lymphoma 1 and unknown 5. Most patients, previously healthy, developed progressive headache which was followed by symptoms and signs involving multiple neuraxis. Major symptoms on admission were headache, nausea, vomitting, visual dimmness, diplopia, hearing disturbance and the major neurologic deficits were papilledema, ocular motor palsy, decreased DTR and neck stiffness. From these clinical findings and CSF test, initially LM was suspected in only 6 patients. In the remaining 6 patients, initial diagnosis were tuberculosis meningitis(3), benigh intracranial hypertension(2) and adjustment disorder(1). In addition to cytology, which was positive in 9 cases, CSF carcinoembryonic antigen(CEA) and neuroimaging played an important role in the early diagnosis of LM. Despite whole brain radiation therapy, all patients worsened and expired 2 weeks-10weeks(median survival, 3 weeks) after the diagnosis.

Mean Corpuscular volume in alcoholics / 대한임상병리학회지

No abstract available.