Eun Hyun Seo

Diagnostic Accuracy of Mini-Mental Status Examination and Revised Hasegawa Dementia Scale for Alzheimer’s Disease

To compare the diagnostic accuracies of the Revised Hasegawa Dementia Scale (HDS-R) and Mini-Mental Status Examination (MMSE) for Alzheimer’s diseases (AD), we administered them simultaneously to 82 AD patients and 82 age- and sex-matched nondemented control subjects. The area under the receiver operator curve (AUC) for AD of the HDS-R (AUCHDS-R) and MMSE (AUCMMSE) were bigger than 0.90 indicating that both tests are useful for detecting AD. However, AUCHDS-R (0.952) was significantly larger than that of the AUCMMSE (0.902) regardless of the educational level of the subjects, indicating that the HDS-R is more accurate than MMSE in diagnosing AD. Moreover, the superiority of the HDS-R (AUCHDS-R = 0.894) to the MMSE (AUCMMSE = 0.704) remained significant in mild AD patients alone, who are the focus of screening. In conclusion, the HDS-R is better than the MMSE as a screening instrument for AD.

Whole-brain Functional Networks in Cognitively Normal, Mild Cognitive Impairment, and Alzheimer’s Disease

The conceptual significance of understanding functional brain alterations and cognitive deficits associated with Alzheimer’s disease (AD) process has been widely established. However, the whole-brain functional networks of AD and its prodromal stage, mild cognitive impairment (MCI), are not well clarified yet. In this study, we compared the characteristics of the whole-brain functional networks among cognitively normal (CN), MCI, and AD individuals by applying graph theoretical analyses to [18F] fluorodeoxyglucose positron emission tomography (FDG-PET) data. Ninety-four CN elderly, 183 with MCI, and 216 with AD underwent clinical evaluation and FDG-PET scan. The overall small-world property as seen in the CN whole-brain network was preserved in MCI and AD. In contrast, individual parameters of the network were altered with the following patterns of changes: local clustering of networks was lower in both MCI and AD compared to CN, while path length was not different among the three groups. Then, MCI had a lower level of local clustering than AD. Subgroup analyses for AD also revealed that very mild AD had lower local clustering and shorter path length compared to mild AD. Regarding the local properties of the whole-brain networks, MCI and AD had significantly decreased normalized betweenness centrality in several hubs regionally associated with the default mode network compared to CN. Our results suggest that the functional integration in whole-brain network progressively declines due to the AD process. On the other hand, functional relatedness between neighboring brain regions may not gradually decrease, but be the most severely altered in MCI stage and gradually re-increase in clinical AD stages.

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.

Association of homocysteine with hippocampal volume independent of cerebral amyloid and vascular burden

This study aimed to clarify whether homocysteine has independent association, not mediated by cerebral beta amyloid protein deposition and vascular burden, with whole brain or hippocampal volume in elderly individuals with normal cognition, mild cognitive impairment, and Alzheimers disease. Nineteen mild cognitive impairment and 24 Alzheimers disease patients were recruited from the Dementia Clinic of the Seoul National University Hospital. Fourteen cognitively normal elderly subjects were also selected from a pool of elderly volunteers. Multiple linear regression analyses showed that plasma total homocysteine level was significantly associated with hippocampal volume even after controlling the degree of global cerebral beta amyloid deposition and vascular burden as well as other potential confounders including age, gender, education, and apolipoprotein E ε4 genotype. On the contrary, plasma total homocysteine level did not show any significant association with whole brain volume. Our finding of the independent negative association between homocysteine and hippocampal volume suggests that homocysteine has a direct adverse effect, not mediated by cerebral beta amyloid deposition and vascular burden, on the hippocampus.

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.