Clinical Significance of Physical Frailty in Subjects With Subjective Cognitive Decline: A Prospective Study With Amyloid PET Data

Background@#and Purpose Physical frailty is known to be closely associated with cognitive impairment and to be an early sign of Alzheimer’s disease. We aimed to understand the characteristics of physical frailty and define factors associated with physical frailty in subjects with subjective cognitive decline (SCD) by analyzing amyloid data. @*Methods@#We prospectively enrolled subjects with SCD from a cohort study to identify predictors for the clinical progression to mild cognitive impairment or dementia from SCD (CoSCo). All of the subjects underwent brain magnetic resonance imaging, and brain amyloid positron-emission tomography (PET) to detect amyloid beta plaques. Self-reported exhaustion, handgrip strength, and gait speed were used to measure physical frailty. @*Results@#Of 120 subjects with SCD, 26 (21.7%) were amyloid-positive in PET. Female (odds ratio [OR]=3.79, p=0.002) and amyloid-PET-positive (OR=3.80, p=0.008) subjects with SCD were at high risks of self-reported exhaustion. Amyloid PET positivity (OR=3.22, p=0.047) and high burden from periventricular white-matter hyperintensity (OR=3.34, 95% confidence interval=1.18–9.46, p=0.023) were significantly associated with a weaker handgrip. The subjects with SCD with self-reported exhaustion and weaker handgrip presented with lower cognitive performance in neuropsychological tests, especially for information processing speed and executive function. Subjects with a slower gait performed worse in visual memory function tests. @*Conclusions@#Amyloid PET positivity was associated with a higher risk of self-reported exhaustion and weaker handgrip in subjects with SCD. The subjects with SCD and physical frailty also performed worse in neuropsychological tests.

The Effect of Daily Low Dose Tadalafil on Cerebral Perfusion and Cognition in Patients with Erectile Dysfunction and Mild Cognitive Impairment

OBJECTIVE: The aims of this study were to investigate the effects of daily low-dose tadalafil on cognitive function and to examine whether there was a change in cerebral blood flow (CBF) in patients with erectile dysfunction (ED) and mild cognitive impairment. METHODS: Male patients aged 50 to 75 years with at least three months of ED (International Index of Erectile Function [IIEF]-5 score ≤ 21) and mild cognitive impairment (Montreal Cognitive Assessment [MoCA] score ≤ 22) were included in the study. The subjects were prescribed a low-dose PDE5 inhibitor (tadalafil 5 mg) to be taken once daily for eight weeks. Changes in MoCA score and single-photon emission computed tomography (SPECT) study between the two time-points were assessed by paired t tests. RESULTS: Overall, 30 male patients were assigned to the treatment group in this study and 25 patients completed the eight-week treatment course. Five patients were withdrawn due to adverse events such as myalgia and dizziness. Mean baseline IIEF and MoCA scores were 7.52 ± 4.84 and 18.92 ± 1.78. After the eight-week treatment, mean IIEF and MoCA scores were increased to 12.92 ± 7.27 (p < 0.05) and 21.8 ± 1.71 (p < 0.05), respectively. Patients showed increased relative regional CBF in the postcentral gyrus, precuneus, and brainstem after tadalafil administration versus at baseline (p < 0.001). CONCLUSION: The results of this prospective clinical study suggest that daily use of tadalafil 5 mg increases some regional CBF and improves cognitive function in patients with ED and mild cognitive impairment.

Different Cortical Thinning Patterns Depending on Their Prognosis in Individuals with Subjective Cognitive Decline

BACKGROUND AND PURPOSE: Subjective cognitive decline (SCD) may be the first stage corresponding to subtle cognitive changes in patients with Alzheimer's disease (AD) spectrum disorders. We evaluated the differences in cortical thinning patterns among patients with SCD who progressed to mild cognitive impairment or dementia (pSCD), those who remained stable (sSCD), and healthy normal controls (NCs).METHODS: We retrospectively recruited SCD subjects (14 pSCD and 21 sSCD cases) and 29 NCs. Structural 3-dimensional-T1-weighted magnetic resonance imaging was performed using a single 1.5 Tesla scanner. Freesurfer software was used to map cortical thickness for group comparisons.RESULTS: Compared with NC group, the sSCD group showed diffuse cortical atrophy associated with bilateral fronto-parieto-temporal area. The pSCD group showed further characteristic cortical atrophy in AD-vulnerable regions including the inferior parieto-temporal and middle temporal areas. Cortical thinning in the bilateral medial frontal areas was observed in patients with sSCD and involved the right inferior temporal and left precentral areas in those with pSCD.CONCLUSIONS: Our study showed that SCD subjects exhibit different cortical thinning patterns depending on their prognosis.

Normal Magnetic Resonance Perfusion Imaging and Atypical Posterior Reversible Encephalopathy Syndrome in Chronic Kidney Disease

BACKGROUND: Posterior reversible encephalopathy syndrome (PRES) is classically characterized by symmetric vasogenic edema in the parietooccipital areas, but may occur at other sites with varying imaging appearances. CASE REPORT: A 55-year old female with chronic kidney disease (CKD) was admitted to the emergency room, presenting with nausea, vomiting and seizure. The initial blood pressure was 145/90 mmHg. Fluid attenuated inversion recovery demonstrated diffuse vasogenic edema in the bilateral cortical and subcortical white matters involving the frontal lobes. Perfusion magnetic resonance imaging (MRP) showed no hyper- or hypoperfusion at blood pressure levels of 140/50 mmHg. A follow-up magnetic resonance imaging at 3 weeks later demonstrated complete resolution of previous lesions. CONCLUSIONS: Earlier reports have demonstrated that PRES can occur in cases of atypical distributions, and features of imaging findings and normotensive settings. It is important to note that PRES is a dynamic process. As a result, we suggest that MRP must be considered in the appropriate temporal framework, to avoid misinterpretation of the other diseases, especially in CKD patients.

Blood Pressure and Heart Rate Variability in Alzheimer's Disease

BACKGROUND AND PURPOSE: Altered blood pressure (BP) and heart rate variations (HRVs) have been reported in Alzheimer's disease (AD). However, it is unclear how these two manifestations are associated with AD. Therefore, the objective of this study was to investigate BP and heart rate variability in AD compared to that in normal controls, patients with subjective memory impairment (SMI), and patients with mild cognitive impairment (MCI). METHODS: Case-control comparisons were made among AD (n=37), MCI (n=24), SMI (n=17), and controls (n=25). All patients underwent clinical and neuropsychological assessments with 24-h ambulatory BP and Holter monitoring. RESULTS: Patients with AD had higher pulse pressures than those in other groups. In addition, AD patients experienced blunted nocturnal BP dipping associated with declining cognitive status. AD patients also had larger ranges of HRV in parasympathetic domains compared to other groups, especially at night. CONCLUSIONS: Our results suggest that diurnal sympathetic and parasympathetic cardiac variability were significantly disturbed in mild cholinesterase-naive AD patients. This may be an indirect sign of disturbed integrity to the sleep-wake cycle in mild AD.

The Effects of Occupational Therapy and Music Therapy on Patients With Mild Cognitive Impairment: A Pilot Study

BACKGROUND: Patients with mild cognitive impairment (MCI) are at an increased risk for developing dementia, especially Alzheimer disease; and pharmacological therapy for MCI is limited. As a result, nonpharmacological mediums have been considered to complement standard drug therapy. In this study, we evaluated the effects of nonpharmacological therapies, occupational therapy and music therapy, on cognitive functions and depressive mood in MCI patients. METHODS: We enrolled patients with MCI from the Mapo Dementia Center and divided them into two groups, group A (n=14) who participated in a cognitive program for 12 months and group B (n=15) who did not participate in a cognitive program. We compared the baseline and followed-up scores of the Korean-version of Mini-Mental State Examination (K-MMSE), the Seoul Neuropsychological Screening Battery (SNSB), and the short version of geriatric depression scale (sGDS) between the two groups. RESULTS: Group A showed improvements in total and language scores in the K-MMSE and digit span backward scores in the SNSB and sGDS. In contrast, group B showed a decline in the Seoul Verbal Learning Test recognition score in the SNSB. Additionally, there were significant intergroup differences in the total and language scores in K-MMSE, the digit span backward score, and the Rey Complex Figure Test-delayed recall scores and depression scores. CONCLUSION: Occupational therapy and music therapy may help to improve cognitive functions and depressive mood in patients with MCI.

Cognitive Impairment in Essential Tremor without Dementia

BACKGROUND AND PURPOSE: Several clinical studies have demonstrated that patients with essential tremor (ET) may have cognitive deficits; however, there are no published data regarding detailed neuropsychological assessments of ET without dementia. We therefore conducted a case-control study of cognitive function in patients with ET. METHODS: The cohort for this study comprised 34 consecutive patients with ET without dementia and 33 age-matched controls, all of who completed a dementia-screening questionnaire and underwent a detailed neuropsychological investigation. RESULTS: Severe impairments were observed in most domains for the ET group compared to the controls, including attention, part of language function, verbal memory, and frontal executive functions. CONCLUSIONS: Our results support the finding that the subclinical cognitive deficits characterized by attention, verbal memory impairments, and executive dysfunction are a clinical feature of ET. In addition, our results also support the finding that age at examination and educational status are the most important risk factors associated with cognitive deficits in patients with ET.

Progressive Multifocal Leukoencephalopathy in a Patient with Systemic Lupus Erythematosus / 대한류마티스학회지

Progressive multifocal leukoencephalopathy (PML) is a rare, serious, and usually fatal demyelinating disease that occurs predominantly in severely immunosuppressed patients. The disease is caused by the infection of oligodendrocytes with JC virus that is widely distributed as a latent infection in the general populations. PML has been described mainly in patients infected with the human immunodeficiency virus. However, other immune-suppressed patients including malignancies and organ transplants can be affected with JC virus infection. Recently it is suggested that rheumatologic diseases, including systemic lupus erythematosus (SLE), rheumatoid arthritis, dermatomyositis, polymyositis, wegener`s granulomatosis be known to be at risk of developing PML. We report a case of PML in a patient with SLE.

Abnormal Integrity of Corticocortical Tracts in Mild Cognitive Impairment: A Diffusion Tensor Imaging Study

Mild cognitive impairment (MCI) has been defined as a transitional state between normal aging and Alzheimer disease. Diffusion tensor imaging (DTI) can estimate the microstructural integrity of white matter tracts in MCI. We evaluated the microstructural changes in the white matter of MCI patients with DTI. We recruited 11 patients with MCI who met the working criteria of MCI and 11 elderly normal controls. The mean diffusivity (MD) and fractional anisotropy (FA) were measured in 26 regions of the brain with the regions of interest (ROIs) method. In the MCI patients, FA values were significantly decreased in the hippocampus, the posterior limb of the internal capsule, the splenium of corpus callosum, and in the superior and inferior longitudinal fasciculus compared to the control group. MD values were significantly increased in the hippocampus, the anterior and posterior limbs of the internal capsules, the splenium of the corpus callosum, the right frontal lobe, and in the superior and the inferior longitudinal fasciculus. Microstructural changes of several corticocortical tracts associated with cognition were identified in patients with MCI. FA and MD values of DTI may be used as novel biomarkers for the evaluation of neurodegenerative disorders.

Diffusion Tensor Imaging in Acute Ischemic Stroke: Usefulness of Fractional Anisotropy

BACKGROUND: Progressing stroke (PS) variably develops from initially the same size and severity, and is most frequently observed in lacunar infarctions. We investigated fractional anisotrophy (FA), mean diffusivity (MD) and infarct volume by using diffusion tensor imaging during the acute phase of ischemic stroke to determine whether these parameters are useful in characterizing and predicting PS. METHODS: In this study, 55 consecutive patients admitted within 24 hours of the onset of their first ischemic stroke were included. NIH stroke scale (NIHSS) and Canadian Neurological scale (CNS) were performed upon admission, twice a day, and at discharge. Modified Rankin scale and Barthel index were also evaluated. PS was defined as a 2-point drop in NIHSS and a 1-point drop in CNS from admission to day 3. A correlation analysis was performed between clinical scale scores and imaging parameters, and the distribution of those values was compared between the two groups with and without PS. RESULTS: Significant correlations were observed between clinical scale scores and infarct volumes. The FA ratio in 14 patients with PS was lower than the patients without PS (p=0.004). Other characteristics including infarct volume and MD ratio were not different. The FA ratio remained as an independent predictor of PS (OR, 1.055; p=0.011). CONCLUSIONS: In acute ischemic stroke within the first 24 hours, only infarct volume was correlated with clinical status. However, patients with PS showed lower FA values, which accounts for rapid and severe vasogenic edema involving the disruption of the cell membrane and axonal fibers. Moreover, FA may be a predictor of PS.

Analysis of SPECT in Two Sub-types of Subcortical Ischemic Vascular Dementia

BACKGROUND: The brain imaging criteria for subcortical ischemic vascular dementia (SIVD), as proposed by Eurkinjuntti, incorporates the two familiar entities, "the lacunar state" and "Binswanger's disease". However, it has not been proven whether these two subtypes of SIVD have common pathophysiological features. This study investigated the changes of the regional cerebral blood flow (rCBF) in the two subsets of SIVD. METHODS: 12 SIVD patients with predominant white matter lesions, 13 patients with predominant multiple lacunar infarctions and 17 controls were evaluated. The general cognitive function and the severity of dementia were measured by using the K-MMSE and the clinical dementia rating scale. The patients simultaneously met both the NINDS-AIREN criteria for probable or possible vascular dementia (VaD) and the Eurkinjuntti's brain imaging criteria for SIVD. 99mTc-ethyl cysteinate dimmer (ECD)-SPECT was performed to measure the rCBF, and statistical parametric mapping (SPM) was applied to the objective analysis of the SPECT data. RESULTS: SPM analysis of the SPECT images revealed that decreased rCBF in the bilateral thalami, anterior cingulated gyri, superior temporal gyri, caudate heads and left parahippocampal gyrus was significant in the patients with SVaD compared to the controls (uncorrected P=0.001). This pattern of rCBF reduction was the same in both the SIVD patients with predominant white matter lesions and with predominant lacunar infarctions. CONCLUSIONS: Our study suggests that the two subsets of SIVD proposed by Eurkinjuntti may have a common functional abnormality, and the Eurkinjuntti's criteria offers a solution for researchers to identify the more homogeneous group of VaD patients.

Cerebral Vasoreactivity by Transcranial Doppler and Brain SPECT in Patients with Unilateral Carotid Stenosis

BACKGROUND: Cerebral vasoreactivity (CVR) is known as having insufficient hemodynamic circulation. However, available information for its clinical interpretation is scant. We attempted to find the relationship of CVR with parameters such as stenosis degree and collateral patterns. METHODS: This study was prospectively conducted in 37 patients with more than 50% angiographically proven unilateral carotid stenosis. The relative change of mean flow velocity before and after an acetazolamide challenge was calculated by transcranial Doppler sonography (TCD) and the results were compared with single photon emission computed tomography (SPECT) results. The degree of stenosis and collateral flow patterns were estimated and classified by conventional angiography. RESULTS: The CVR of middle cerebral artery (MCA) was significantly decreased in the ipsilateral side to the carotid stenosis (p<0.05). The CVR impairment was more severe when symptomatic stenosis was present (p=0.04). There was a significant correlation between the degree of carotid stenosis and the CVR (p<0.01). In the area of impaired CVR by SPECT, the estimated CVR was significantly lower (p<0.05), even to the negative value, implying that there is an actually steal phenomenon in that area. CONCLUSIONS: TCD is a useful tool for the assessment of CVR, which can give diverse clinical information based upon the degree of stenosis.

A Case of Spontaneous Intracranial Hypotension presented as Bilateral Abducens Nerve Palsy without Postural Headache

No abstract available.

Changes of Regional Cerebral Blood Flow in Left Anterior Thalamic Infarction: Analysis of 99mTc-Ethyl Cysteinate Dimer (ECD) SPECT by using Statistical Parametric Mapping

BACKGROUND: The thalamus has multiple connections with areas of the cerebral cortex involved in arousal and cognition. Thalamic damage has been reported to be associated with variable neuropsychological dysfunctions and dementia. This study investigates the changes of regional cerebral blood flow (rCBF) by using SPM analysis of 99mTc-ECD SPECT and examining the neuropsychological abnormalities of 4 patients with anterior thalamic infarctions. METHODS: Four patients with left anterior thalamic infarctions and eleven normal controls were evaluated. K-MMSE and the Seoul Neuropsychological Screening Battery were performed within 2 days after stroke. The normalized SPECT data of 4 patients were compared to those of 11 controls for the detection of areas with decreased rCBF by SPM analysis. RESULTS: All 4 patients showed anterograde amnesia in their verbal memory, which was not improved by recognition. Dysexecutive features were occasionally present, such as decreased word fluency and impaired Stroop test results. SPM analysis revealed decreased rCBF in the left supramarginal gyrus, the superior temporal gyrus, the middle and inferior frontal gyrus, the medial dorsal and anterior nucleus of the left thalamus. CONCLUSIONS: The changes of rCBF in patients with left anterior thalamic infarctions may be due to the remote suppression on metabolism by the interruption of the cortico-subcortial circuit, which connects the anterior thalamic nucleus and various cortical areas. The executive dysfunction and dysnomia may be caused by the left dorsolateral frontal dysfunction of the thalamocortical circuit. Anterograde amnesia with storage deficit may be caused by the disruption of mamillothalamic tract.

The Effect and the Mechanism of Action of High Frequency Electrical Stimulation of Subthalamic Nucleus on Status Epilepticus Induced by Lithium-Pilocarpine of Rat / 대한간질학회지

OBJECTIVES: Deep brain stimulation (DBS) of subthalamic nuclei (STN) is one of the current modalities of refractory epilepsy, but its exact mechanism and route of action have not been elucidated yet. We investigated the effect of STN stimulation on the development and propagation of seizures in the rats with lithium-pilocarpine induced status epilepticus in its functional anatomy. METHODS: Both pilocarpine injection and high frequency stimulation on STN (HFSSTN) were provided to rats (STN group, n=12), but pilocarpine injection with no stimulation was done on the sham group (n=8). The latency to first discrete ictal discharges and the latency to status epilepticus (SE) were analyzed and the electrical stimulation lasted for 30, 60, 90, 120 minutes after its first discrete spikes. After stimulation, the rats were immediately decapitated for immunohistochemistry and histologic examination. RESULTS: Both the latency to first discrete ictal discharges and the latency to the onset of SE were delayed in the STN group than in the sham group. The latency to the first SE was also more delayed in the STN group (42.7+/-7.9 min) than in the sham group (p<0.05). Remarkably, there was marked Fos immunoreactivity (FIR) on the reticular thalamic nuclei in the STN group, but not in the sham group. CONCLUSIONS: Increased FIR in the reticular thalamic nuclei during HFSSTN suggested that the facilitation of the inhibitory thalamic output prevented generalized motor seizure behavior. We assume that HFSSTN has a pivotal role in the suppression or progression to SE, but cannot prevent seizure onset.

A Electrodiagnostic Study on Relationship of the Double Crush Syndrome to Carpal Tunnel Syndrome: a Preliminary Study

BACKGROUND: The concept of "double crush syndrome (DCS)"-a proximal compressive lesion making the distal nerve more vulnerable to injury-is an intriguing hypothesis. However, recent studies did not show unitary results. This study was preliminarily undertaken in order to clarify the causal relationship of proximal compressive lesion and carpal tunnel syndrome (CTS) in an electrophysiologic aspect. METHODS: In the period between June 1998 and June 1999 there were 24 patients with CTS(33 limbs with CTS). With these CTS patients, thorough electrodiagnostic studies were performed to discover coexisting proximal compressive lesions along the median nerve and its corresponding cervical root lesions. RESULTS: In 10 of these limbs (30%), there was a electrodiagnostically-proven coexisting proximal compressive lesion(all cervical radiculopathies). But only 1 limb (3%) had an anatomically responsible association. Finally only 1 limb (3%) with CTS had a possibility of DCS. CONCLUSIONS: CTS and cervical radiculopathy are common disorders, so there is a high possibility of coexisting as a double primary lesion without a pathophysiological relationship. Our results do not support the double crush hypothesis. However, the possibility of a reversed double crush syndrome is suggested.

The Effects of the decortication on pulmonary function in tuberculous empyema / 결핵

BACKGROUND: The purpose decortication is to eliminate the infection focus and to improve the decreased lung function due to chronic empyema. However, lung function is not improved in all cases. It would be clinically useful it we could predict preoperatively whether lung function would improve after decortication. The purpose of this study is to find useful indices for predicting the possible improvement of lung function after decortication. METHOD: The medical records of 37 tuberculous empyema patients who underwent pleural decortication were analyzed retrospectively from 1990 to 1996. The measurements of preoperative and postoperative forced vital capacity(FVC) were used for evaluating the effects of decortication. RESULTS: The sex ratio was 29 : 8 (male to female), and the median age was 34 years. The time interval between the formation of empyema and operation was 1 month to 30 years. Postoperative pulmonary function test was performed 5.4±2.6 months later. FVC(forced vital capacity) was significantly increased from 2.77±0.67(L) to 2.95± 0.81(L). Interestingly, postoperative pulmonary function was significantly improved in patients who were less than 40 years old, within 4 months after diagnosis of tuberculous empyema, in the group with FVC of less than 60% of the predicted value and in the absence of calcification. CONCLUSION: The improvement of lung function after decortication was expected in patients younger than 40 years old, within 4 months after diagnosis of tuberculous empyema, in the group having less than 60% of the predicted FVC, without calcification.

The Usefulness of Serologic Diagnosis for Tuberculosis with Two Rapid Immunochromatographic Assay Devices / 결핵

BACKGROUND: Many diagnostic tests have developed to diagnose tuberculosis and other mycobacterial diseases but the diagnosis of tuberculosis relies largely on radiological findings and acid-fast staining of sputum and/or culture. Recently, new serologic diagnostic methods, which are safe and easy to use have been introduced into Korea. In this study, the usefulness of serologic diagnosis for tuberculosis and the disease pattern induced variation of the test were evaluated. METHODS: Serological assay was performed upon 108 patients with two test kits, the ICT tuberculosis and the BioSign(TM) TB, which are based upon a rapid immunochromatographic assay technique, capable of being interpreted within 15 minutes. The case groups consisted of 61 patients with active pulmonary tuberculosis(36 patients), extrapulmonary tuberculosis(3 patients), or both (22 patients). Control groups consisted of 47 patients with inactive old pulmonary tuberculosis (17 patients), nontuberculous pulmonary disease(16 patients) and nonpulmonary cardiac disease(14 patients). RESULTS: The diagnostic sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) of the ICT tuberculosis were 64.3%, 91.5%, 90.0% and 68.3% respectively. The diagnostic sensitivity, specificity, PPV and NPV of the BioSign(TM) TB were 76.5%, 95.3%, 94.1% and 78.8% respectively. Differences in sensitivity were not significant between patients with previous history of tuberculosis or patients without prior history of tuberculosis. The ICT tuberculosis test showed higher sensitivity in pulmonary tuberculosis patients (76.5%) than extrapulmonary tuberculosis patients (33.3%). There was no difference in sensitivity between patients with or without cavitary lesion by chest X-ray. CONCLUSION: Considering high specificity and PPV, serologic diagnosis using a rapid immunochromatographic assay device is another helpful diagnostic method in the diagnosis of tuberculosis, when combined with previous diagnostic methods such as chest X-ray, microbiologic study but it has limitation in terms of confirming the diagnosis for tuberculosis as the only diagnostic method because of relatively low sensitivity and NPV.

Two Cases of Rhinocerebral Mucormycosis with Perineural Extension to the Pons

Rhinocerebral mucormycosis is a very rare, but mostly fatal fungal infection, usually found in diabetic or other immunocompromised hosts. It has a characteristic pattern of spread, invasion of vessel walls with subsequent local thrombotic infarction or direct invasion. But we found two cases contrast to these typical patterns of spread. Our cases initially originated in the nasal cavity and progressed to the cavernous sinus in usual manner, but after then, extended along the trigeminal nerve into the pons. MRI demonstrated the perineural spread, which was confirmed by pathology.

Two Cases of Rhinocerebral Mucormycosis with Perineural Extension to the Pons

Rhinocerebral mucormycosis is a very rare, but mostly fatal fungal infection, usually found in diabetic or other immunocompromised hosts. It has a characteristic pattern of spread, invasion of vessel walls with subsequent local thrombotic infarction or direct invasion. But we found two cases contrast to these typical patterns of spread. Our cases initially originated in the nasal cavity and progressed to the cavernous sinus in usual manner, but after then, extended along the trigeminal nerve into the pons. MRI demonstrated the perineural spread, which was confirmed by pathology.