Jee Hyang Jeong

Multiplex analysis of cytokines in the serum and cerebrospinal fluid of patients with Alzheimer's disease by color-coded bead technology.

Background and purpose The availability and promise of effective treatments for neurodegenerative disorders are increasing the importance of early diagnosis. Having molecular and biochemical markers of Alzheimers disease (AD) would complement clinical approaches, and further the goals of early and accurate diagnosis. Combining multiple biomarkers in evaluations significantly increases the sensitivity and specificity of the biochemical tests. Methods In this study, we used color-coded bead-based Luminex technology to test the potential of using chemokines and cytokines as biochemical markers of AD. We measured the levels of 22 chemokines and cytokines in the serum and cerebrospinal fluid (CSF) of 32 de novo patients (13 controls, 11 AD, and 8 Parkinsons disease [PD]). Results MCP-1 was the only cytokine detectable in CSF, and its levels did not differ between control and disease groups. However, the serum concentration of eotaxin was significantly higher in AD patients than in the control group. Conclusions The analysis of multiple inflammatory mediators revealed marginal differences in their CSF and serum concentrations for the differential diagnosis of AD and PD. These results provide evidence that immunological responses are not major contributors to the pathogenesis of AD and PD.

Gender differences in risk factors for transition from mild cognitive impairment to Alzheimer’s disease: A CREDOS study

BACKGROUND Women are subject to a disproportionate burden from Alzheimers disease (AD) and sex differences exist in treatment response and prognosis of the disease. Yet gender-specific risk factors have not been widely studied. We aimed to investigate gender-specific risk factors for AD in subjects with mild cognitive impairment (MCI). METHODS Participants (n=294) with MCI were recruited from a nationwide, prospective cohort study of dementia and were followed for a median (range) of 13.8 (6.0-36.0) months. Sex-stratified associations of progression to AD with baseline characteristics were explored. RESULTS Seventy-four individuals (25.2%) developed incident dementia (67 AD) during follow-up. Significant risk factors for probable AD differed by sex. In men, the significant risk factors were severe periventricular white matter hyperintensities, and poorer global cognitive function. In women, older age, clinically significant depressive symptoms at baseline, and positive APOE ε4 alleles were the significant risk factors. CONCLUSIONS Risk factors for progression from MCI to probable AD differed in men and women. These results may translate to gender-specific preventative or therapeutic strategies for patients with MCI.

Hippocampal volume and shape in pure subcortical vascular dementia.

The purposes of the present study were to explore whether hippocampal atrophy exists in pure subcortical vascular dementia (SVaD) as defined by negative (11)C-Pittsburg compound-B (PiB(-)) positron emission tomography and to compare hippocampal volume and shape between PiB(-) SVaD and PiB positive (PiB(+)) Alzheimers disease (AD) dementia. Hippocampal volume and shape were compared among 40 patients with PiB(-) SVaD, 34 with PiB(+) AD, and 21 elderly with normal cognitive function (NC). The normalized hippocampal volume of PiB(-) SVaD was significantly smaller than NC but larger than that of PiB(+) AD (NC > PiB(-) SVaD > PiB(+) AD). Both PiB(-) SVaD and PiB(+) AD patients had deflated shape changes in the cornus ammonis (CA) 1 and subiculum compared with NC. However, direct comparison between PiB(-) SVaD and PiB(+) AD demonstrated more inward deformity in the subiculum of the left hippocampus in PiB(+) AD. PiB(-) SVaD patients did have smaller hippocampal volumes and inward shape change on CA 1 and subiculum compared with NC, suggesting that cumulative ischemia without amyloid pathology could lead to hippocampal atrophy and shape changes.

Interchanging scores between Clinical Dementia Rating scale and Global Deterioration Scale

&NA; Clinical Dementia Rating (CDR) scale and Global Deterioration Scale (GDS) are commonly used to measure the severity of dementia. However, no specific rules are available to convert the scores of CDR into those of GDS and vice versa. Using a semi‐structured interview, two examiners independently rated CDR and GDS in 78 patients with dementia and 34 controls. Regression analysis showed a curvilinear relationship between CDR and GDS. This curve may provide a rule to interchange the scores of GDS and CDR (or Sum of Boxes of CDR).

Semantic dementia combined with motor neuron disease.

Up to 20% of patients with behavioural variants of frontotemporal dementia (FTD) also have motor neuron disease (MND); conversely, this comorbidity is rare in patients with language variants of FTD. A few patients have been reported with semantic dementia (SD) combined with MND. However, these patients demonstrated the clinical features of MND in the advanced stage. We report a patient with SD who also demonstrated MND symptoms in an earlier stage of the disease. A 61-year-old man visited our memory disorder clinic as a result of language disturbance and dysarthria of 8 months duration and facial recognition impairment of 3 months duration. Neuropsychological tests revealed anomic aphasia, prosopagnosia, and decreased semantic fluency. A brain MRI revealed significant atrophies localized in both anterior temporal lobes with a greater prominence on the right side. Clinical examination and electrophysiological studies confirmed a diagnosis of MND 17 months after the onset of the disease.

Structural brain changes after traditional and robot-assisted multi-domain cognitive training in community-dwelling healthy elderly.

The purpose of this study was to investigate if multi-domain cognitive training, especially robot-assisted training, alters cortical thickness in the brains of elderly participants. A controlled trial was conducted with 85 volunteers without cognitive impairment who were 60 years old or older. Participants were first randomized into two groups. One group consisted of 48 participants who would receive cognitive training and 37 who would not receive training. The cognitive training group was randomly divided into two groups, 24 who received traditional cognitive training and 24 who received robot-assisted cognitive training. The training for both groups consisted of daily 90-min-session, five days a week for a total of 12 weeks. The primary outcome was the changes in cortical thickness. When compared to the control group, both groups who underwent cognitive training demonstrated attenuation of age related cortical thinning in the frontotemporal association cortices. When the robot and the traditional interventions were directly compared, the robot group showed less cortical thinning in the anterior cingulate cortices. Our results suggest that cognitive training can mitigate age-associated structural brain changes in the elderly. Trial Registration ClnicalTrials.gov NCT01596205

Seoul criteria for PiB(-) subcortical vascular dementia based on clinical and MRI variables.

Objective: The purpose of this study was to propose new criteria for differentiating Pittsburgh compound B (PiB)-negative from PiB-positive subcortical vascular dementia (SVaD) using clinical and MRI variables. Methods: We measured brain amyloid deposition using PiB-PET in 77 patients with SVaD. All patients met DSM-IV criteria for vascular dementia and had severe white matter hyperintensities on MRI, defined as a cap or band ≥10 mm as well as a deep white matter lesion ≥25 mm. Eleven models were considered to differentiate PiB(−) from PiB(+) SVaD using 4 variables, including age, number of lacunes, medial temporal atrophy (MTA), and APOE ε4. The ideal cutoff values in each of the 11 models were selected using the highest Youden index. Results: A total of 49 of 77 patients (63.6%) tested negative for PiB retention, while 28 (36.4%) tested positive for PiB retention. The ideal model for differentiating PiB(−) from PiB(+) SVaD was as follows: age ≤75 years, ≥5 lacunes, and MTA ≤3, which together yielded an accuracy of 67.5%. Conclusion: When patients meet the DSM-IV criteria for vascular dementia and also have severe white matter hyperintensities, younger age, greater number of lacunes, and lesser MTA, these are predictive of a PiB(−) scan in patients with SVaD. Classification of evidence: This study provides Class II evidence that the combination of younger age, greater number of lacunes, and lesser MTA identifies patients with SVaD at lower risk of Alzheimer disease pathology.

Relationships between 24-Hour Blood Pressures, Subcortical Ischemic Lesions, and Cognitive Impairment.

Background and Purpose The most important treatment for subcortical vascular dementia (SVaD) is controlling the blood pressure (BP). However, the few studies that have investigated the relationships between diurnal BP rhythm and subcortical ischemic vascular cognitive impairment have produced inconclusive results. In the study presented here, the 24-hour BP values of three groups of subjects-patients with subcortical vascular mild cognitive impairment (SvMCI), patients with SVaD, and normal controls-were compared using working criteria and 24-hour ambulatory BP (ABP) monitoring. Methods The subjects (42 patients with SVaD, 37 patients with SvMCI, and 30 controls) were selected according to the studys inclusion/exclusion criteria. All subjects underwent brain magnetic resonance (MR) imaging and MR angiography, detailed neuropsychological testing, and 24-hour ABP monitoring. Results The prevalence of nondippers differed markedly between the control group and both the SVaD and SvMCI groups. Loss of nocturnal dipping was significantly associated with SVaD [odds ratio (OR), 4.827; 95% confidence interval (CI), 1.07-12.05]. Conclusions It was found that SVaD is associated with loss of nocturnal BP dipping combined with increased pulse pressure and systolic BP (SBP) variability. Correction of these factors could therefore be important in the prevention of SVaD, independent of measures used to reduce BP.

Elevation of the Plasma Aβ40/Aβ42 Ratio as a Diagnostic Marker of Sporadic Early-Onset Alzheimer's Disease.

BACKGROUND Although plasma amyloid-β (Aβ) levels have been evaluated as a possible diagnostic marker of Alzheimers disease (AD), the findings are inconsistent. OBJECTIVE The present study aimed to validate plasma levels of Aβ40, Aβ42, and the Aβ40/Aβ42 ratio as biomarkers of AD in subjects with early-onset AD (EOAD) without familial AD genetic mutations. METHODS Patients with sporadic EOAD (sEOAD) were prospectively recruited by nine neurology clinics. Plasma levels of Aβ40 and Aβ42 were measured using a sandwich enzyme-linked immunosorbent assay (ELISA) in 100 sEOAD (50-69 year-old) and 46 age-matched normal control subjects (50-72 year-old). Cerebrospinal fluid (CSF) was obtained from 32 sEOAD subjects and 25 controls. The integrity of the blood-brain barrier was assessed using the CSF/plasma albumin ratio. RESULTS The plasma levels of Aβ42 were significantly lower, while the Aβ40/Aβ42 ratio was significantly higher in sEOAD patients than in controls. The levels of Aβ40, Aβ42, and the Aβ40/Aβ42 ratio did not differ in relation to the APOEɛ4 allele. The CSF/plasma albumin ratio was comparable between the two groups, and the plasma parameters of Aβ proteins were not significantly associated. A multivariate analysis revealed that an increased Aβ40/Aβ42 ratio is valuable for the discrimination of sEOAD from controls (β=0.344, p=0.000). The area under the ROC curve for the Aβ40/Aβ42 ratio was 0.76, and a cut-off ratio of 5.87 was suggested to have 70% sensitivity and 68% specificity. CONCLUSION The plasma Aβ40/Aβ42 ratio had moderate validity for the discrimination of sEOAD patients from age-matched controls.

Saccadic Palsy after Cardiac Surgery: Serial Neuroimaging Findings during a 6-Year Follow-Up

Background Patients who develop horizontal and vertical saccadic palsy after cardiac surgery have rarely been described. Although most such patients exhibit distinct neurological deficits, their brain MRI findings are almost normal. In addition, functional neuroimaging of such patients has never been reported. Case Report A 43-year-old woman with dysarthria, dysphagia, and horizontal and vertical saccadic palsy after cardiac surgery was followed up for about 6 years; serial brain MRIs has been performed during this period, including susceptibility-weighted imaging (SWI) and [18F]-fluoro-2-deoxy-D-glucose positron emission tomography (FDG-PET). Multiple microbleeds in the cerebral cortex, cerebellum, and brainstem, and glucose hypometabolism in the brainstem, cerebellum, and multiple cortical areas. Conclusions To the best of our knowledge, this is the first reported case of saccadic palsy after cardiac surgery with serial SWI and [18F]-FDG-PET performed to explore the possible cerebral lesions.