Shin Gyeom Kim

Posterior cingulate cortex atrophy and regional cingulum disruption in mild cognitive impairment and Alzheimer's disease

This study aimed to investigate the atrophy of the posterior cingulate cortex (PCC) and medical temporal lobe (MTL) structures (i.e., the entorhinal cortex (ERC) and hippocampus) and the regional disruption of the cingulum bundle in mild cognitive impairment (MCI) and Alzheimers disease (AD) patients. The relationships between atrophy of these structures and regional cingulum disruption were also explored. Three-dimensional MRI and diffusion tensor imaging were applied to 19 MCI, 19 probable AD patients, and 18 normal controls (NC). Fractional anisotropy (FA) values were obtained from three different regions of the cingulum. Both MCI and AD patients showed decreased PCC volumes compared with NC. ERC atrophy was also significant in AD and MCI, while hippocampus atrophy was significant only in AD. MCI patients showed a significant FA decrease in the parahippocampal cingulum (PH-C), whereas AD patients had lower FA values in the posterior cingulate cingulum (PC-C) and PH-C, as compared with NC. However, the middle cingulate cingulum (MC-C) showed no significant FA differences between groups. Moreover, the volumes of MTL structures were significantly correlated with PH-C and PC-C FA values. In terms of PCC functional deficit in MCI or early AD, our results support both the direct effect of PCC atrophy itself and the indirect effect of cingulum fiber degeneration secondary to MTL atrophy.

Microstructural alteration of the anterior cingulum is associated with apathy in Alzheimer disease.

OBJECTIVES To identify regional alterations of white matter integrity associated with apathy in Alzheimer disease (AD). DESIGN Cross-sectional study. SETTING University Dementia Clinic. PARTICIPANTS Fifty-one very mild or mild probable AD subjects. INTERVENTION Volumetric magnetic resonance imaging with diffusion tensor imaging. MEASUREMENTS Volume of interest analyses were performed to compare regional fractional anisotropy (FA) between apathy and apathy-free group, and to test linear relationship between regional FA and apathy severity. Apathy was assessed by the Neuropsychiatric Inventory. RESULTS Apathy group showed significantly lower FA values than apathy-free group in the left anterior cingulum (A-C), regardless of concomitant depression and psychotropic medications. Left A-C FA values also had significant linear relationship with apathy-composite scores as a measure of apathy severity, even after controlling gray matter density of the ipsilateral anterior cingulate cortex. CONCLUSIONS Our findings support that communication failure between the anterior cingulate cortex and other brain structures via the A-C contributes to the development and aggravation of apathy in AD, additionally supporting the general notion of disconnection syndrome for clinical manifestation of AD.

Normative study of the Stroop Color and Word Test in an educationally diverse elderly population

The purpose of this study was to explore the effects of demographic variables on Stroop Color and Word Test (SCWT) performance in an educationally diverse elderly population and to provide normative information.

Total Scores of the CERAD Neuropsychological Assessment Battery: Validation for Mild Cognitive Impairment and Dementia Patients With Diverse Etiologies

OBJECTIVES This study aimed to validate the two total scores (TS-I and TS-II) of the Consortium to Establish a Registry for Alzheimer Disease neuropsychological battery (CERAD-NP) for a large elderly population including mild cognitive impairment (MCI) and dementia patients with various etiologic backgrounds. The authors also investigated whether the addition of frontal-executive function score can improve the discrimination accuracy of the total scores for dementia and MCI. DESIGN, SETTING, AND PARTICIPANTS One thousand three hundred thirty-six normal comparison (NC), 583 dementia (420 AD, 111 non-AD dementia, and 52 mixed AD with non-AD dementia), and 250 MCI (223 amnestic and 27 nonamnestic MCI) individuals living in the community were included (all aged 60 years and older). RESULTS Both TS-I and TS-II were highly correlated with other global cognitive and functional scales. Both total scores showed, though modest, superior NC versus MCI discrimination ability to Mini-Mental State Examination (MMSE). Their discrimination ability for NC versus dementia was excellent and significantly better, especially in discriminating very mild dementia, than MMSE. The addition of frontal-executive test score to TS-I or TS-II did not make a significant improvement in dementia or MCI discrimination ability. Both of them also showed higher test-retest and interrater reliability than MMSE or any individual neuropsychological tests in the CERAD-NP. CONCLUSION These results strongly support the validity and usefulness of CERAD total scores for early detection and progression monitoring of MCI and dementia in clinical and research settings.

Discrimination of normal aging, MCI and AD with multimodal imaging measures on the medial temporal lobe

This study aimed to compare the discrimination accuracy of hippocampal volume (HC-Vol), parahippocampal cingulum fractional anisotropy (PHC-FA), hippocampal glucose metabolism (HC-Glu), and any combination of the three measurements among normal control (NC), mild cognitive impairment (MCI), and Alzheimers disease (AD). Three-dimensional MRI, diffusion tensor imaging, and FDG-PET were applied to age- and gender-matched 17 NC, 17 MCI, and 17 mild AD patients. Subjects also underwent a neuropsychological test battery including three verbal episodic memory tests. Logistic regression analyses were systematically conducted to select the best model for between-group discrimination. PHC-FA plus HC-Vol model, HC-Glu only model, and the model combining all three modalities were finally chosen for NC vs. MCI (discrimination accuracy: 79.4%), MCI vs. AD (73.5%), and NC vs. AD discrimination (94.1%), respectively. All the three imaging measures also showed significant correlation with all three episodic memory tests. These findings support that each imaging measure, respectively, and their combination have a stage-specific potential as a useful neuroimaging marker for detection and progression monitoring of early stage of AD.

Validity of the telephone interview for cognitive status (TICS) and modified TICS (TICSm) for mild cognitive imparment (MCI) and dementia screening

This study aimed to validate the TICS and modified TICS (TICSm) in Korean elderly population and to compare MCI and dementia screening ability between TICS and TICSm. TICS and TICSm were administered to 70 cognitively normal (CN), 75 MCI, and 85 dementia subjects, with mini-mental state examination (MMSE) and other cognitive and functional measures. TICS and TICSm scores were highly correlated with other global cognitive and functional scores. The CN vs. dementia discrimination ability of both instruments was as excellent as that of MMSE (sensitivity/specificity at optimal cutoff: 87.1/90.1 for TICS; 88.2/90.0 for TICSm). Although their CN vs. MCI discrimination performances were comparable to that of MMSE, they were far from perfect (sensitivity/specificity: 69.3/68.6 for TICS; 73.3/67.1 for TICSm). There was no significant difference in dementia or MCI screening accuracy between TICS and TICSm. Both of them also showed high test-retest reliability. Our findings indicate that TICS and TICSm are reliable and as valid as MMSE in regard of screening cognitively impaired elderly. In terms of the comparison between TICSm and TICS, however, TICSm has little advantage over TICS for screening dementia and even MCI, in spite of longer administration time and more efforts required.

Neural Correlates of the Clock Drawing Test Performance in Alzheimer’s Disease: A FDG-PET Study

Background/Aim: This study aimed to identify the functional neuroanatomical correlates of impaired clock drawing test (CDT) performance in patients with Alzheimer’s disease (AD). Method: The CDT was administered to 71 patients with AD, and regional cerebral glucose metabolism (rCMglc) was measured by positron emission tomography (PET). Correlations between CDT scores and rCMglc were examined on a voxel-by-voxel basis. Results: Significant positive correlations were found between CDT performance and rCMglc in the right inferior parietal lobule and right posterior cingulate cortex. Conclusion: These results provide the first PET evidence that poor CDT performance in patients with AD is closely related to the functional decline in the right hemisphere, especially the right parietal cortex.

Relationship of Amyloid-Beta Burden With Age-At-Onset in Alzheimer Disease

OBJECTIVE To investigate the relationship between in vivo brain amyloid-beta (Aβ) burden, measured by C-labeled Pittsburgh Compound B (C-PiB) retention, and age-at-onset in patients with Alzheimer disease (AD). DESIGN Cross-sectional study. SETTING University Dementia Clinic. PARTICIPANTS Twenty-two AD patients including 11 early-onset AD (EOAD: onset <65 years) and 11 late-onset AD (LOAD: onset ≥65years) cases with matched dementia severity, duration of illness, and apolipoprotein E ε4 allele number. INTERVENTION C-PiB positron emission tomography scans. MEASUREMENTS Both region of interest and voxel-based analyses were performed to compare C-PiB retention between EOAD and LOAD groups, and to test linear relationship between age-at-onset and C-PiB retention. RESULTS Both region of interest (ROI) and voxel-based analyses revealed that EOAD patients had significantly higher C-PIB retentions than LOAD patients in diffuse brain regions including frontal, lateral parietal, lateral temporal, and occipital cortex, and basal ganglia. Subgroup analyses showed that negative correlation between age-at-onset and C-PiB retention was significant in LOAD but not in EOAD. CONCLUSIONS Our finding of a heavier Aβ burden in the brain of living EOAD patients than LOAD patients is in agreement with those from postmortem studies. The inverse relationship between age-at-onset and Aβ burden is possibly associated with aging-related decrease of brain or cognitive reserve and with aging-related increase of brain vulnerability.

Association analysis of COMT polymorphisms with schizophrenia and smooth pursuit eye movement abnormality.

Schizophrenia is a multifactorial disorder characterized by the contribution of multiple susceptibility genes that may act in conjunction with epigenetic processes and environmental factors. The catechol-O-methyltransferase (COMT) gene, which is located in the 22q11 microdeletion, has been considered as a candidate gene for schizophrenia because of its ability to degrade catecholamines, including dopamine. In a genetic analysis, neurophysiological endophenotype in schizophrenia, such as smooth pursuit eye movement (SPEM) disturbance, is considered to be a good trait marker, because it may be under more direct genetic control. This study was performed to examine the genetic association of COMT polymorphisms with the risk of schizophrenia and SPEM abnormality in a Korean population. Six single-nucleotide polymorphisms of COMT were genotyped by TaqMan assay. Their genetic effects on the risk of schizophrenia were analyzed in 354 patients and 396 controls using χ2 analyses. Among the schizophrenic patients, 166 subjects were selected for association analyses of COMT polymorphisms with SPEM abnormality. From the six COMT polymorphisms, rs6267 showed an association with the reduced risk of schizophrenia after correction (Pcorr = 0.02). In analysis of SPEM abnormality, no significant associations were detected with COMT polymorphisms. The results of the present study provide the evidence that in a Korean population, COMT on the 22q11 locus is likely involved in the development of schizophrenia, but not in the SPEM function abnormality.

Is a 9‐month treatment sufficient in tuberculous enterocolitis? A prospective, randomized, single‐centre study

Background : Tuberculosis has increased in parallel with the acquired immunodeficiency syndrome epidemic and the use of immunosuppressive therapy, and the growing incidence of extra‐pulmonary tuberculosis, especially with intestinal involvement, reflects this trend. However, the duration of anti‐tuberculous therapy has not been clarified in intestinal tuberculosis.