Hyo Jung Choi

Influence of APOE Genotype on Whole-Brain Functional Networks in Cognitively Normal Elderly

This study aimed to investigate the influence of apolipoprotein E (APOE) ε4 allele on whole-brain functional networks in cognitively normal (CN) elderly by applying graph theoretical analysis to brain glucose metabolism. Eighty-six CN elderly [28 APOE ε4 carriers (ε4+) and 58 non-carriers (ε4-)] underwent clinical evaluation and resting [18F] fluorodeoxyglucose positron emission tomography scan. Whole-brain functional networks were constructed from correlations of the 90 regions of interest using the automated anatomical labeling template, and analyzed using graph theoretical approaches. The overall small-world property seen in ε4- was preserved in ε4+. However, both local clustering and path length were lower in ε4+ compared to ε4-. In terms of the hubs of functional networks, ε4+ showed decreased centrality of the right hippocampus but increased centrality of several brain regions associated with the default mode network compared to ε4-. Our results indicate that genetic vulnerability to Alzheimer’s disease may alter whole-brain functional networks even before clinical symptoms appear.

Functional Neuroanatomical Correlates of The Frontal Assessment Battery Performance in Alzheimer Disease A FDG-PET Study

Background/Objectives: We aimed to elucidate the functional neuroanatomical correlates of Frontal Assessment Battery (FAB) performances by applying [18F]fluorodeoxyglucose positron emission tomography (FDG-PET) to a large population of patients with Alzheimer disease (AD). Methods: The FAB was administered to 177 patients with AD, and regional cerebral glucose metabolism (rCMglc) was measured by FDG-PET scan. Correlations between FAB scores and rCMglc were explored using both region-of-interest-based (ROI-based) and voxel-based approaches. Results: The ROI-based analysis showed that FAB scores correlated with the rCMglc of the dorsolateral prefrontal cortices. Voxel-based approach revealed significant positive correlations between FAB scores and rCMglc which were in various cortical regions including the temporal and parietal cortices as well as frontal regions, independent of age, gender, and education. After controlling the effect of global disease severity with Mini-Mental State Examination score, significant positive correlation was found only in the bilateral prefrontal regions. Conclusions: Although FAB scores are influenced by temporoparietal dysfunction due to the overall progression of AD, it likely reflects prefrontal dysfunction specifically regardless of global cognitive state or disease severity in patients with AD.

Screening Ability of Subjective Memory Complaints, Informant-Reports for Cognitive Decline, and Their Combination in Memory Clinic Setting

Objective This study aimed to compare the accuracy of subjective memory complaints, informant-reports for cognitive declines, and their combination for screening cognitive disorders in memory clinic setting. Methods One-hundred thirtytwo cognitively normal (CN), 136 mild cognitive impairment (MCI), and 546 dementia who visited the memory clinic in the Seoul National University Hospital underwent standardized clinical evaluation and comprehensive neuropsychological assessment. The Subjective Memory Complaints Questionnaire (SMCQ) and the Seoul Informant Report Questionnaire for Dementia (SIRQD) were used to assess subjective memory complaints and informant-reports for cognitive declines, respectively. Results Both SMCQ and SIRQD showed significant screening ability for MCI, dementia, and overall cognitive disorder (CDall: MCI plus dementia) (screening accuracy: 60.1–94.6%). The combination of SMCQ and SIRQD (SMCQ+SIRQD) was found to have significantly better screening accuracy compared to SMCQ alone for any cognitive disorders. SMCQ+SIRQD also significantly improved screening accuracy of SIRQD alone for MCI and CDall, but not for dementia. Conclusion Our findings suggest that the combined information of both subjective memory complaints and informant-reports for cognitive declines can improve MCI screening by each individual information, while such combination appears not better than informant-reports in regard of dementia screening.

Associations of thyroid hormone serum levels with in-vivo Alzheimer’s disease pathologies

BackgroundThe present study investigated the relationships between thyroid hormone serum levels or thyroid-stimulating hormone (TSH) and two Alzheimer’s disease (AD)-specific biomarkers, cerebral amyloid beta (Aβ) burden and glucose metabolism, in AD-signature brain regions in cognitively normal (CN) middle-aged and older individuals.MethodsThis study assessed 148 CN individuals who received comprehensive clinical and neuropsychological assessments that included 11C-Pittsburgh Compound B (PiB)-positron emission tomography (PET) scans, 18F-deoxyglucose (FDG)-PET scans, and the quantification of serum triiodothyronine (T3), free T3, free thyroxine (fT4), and TSH levels.ResultsAll participants were clinically euthyroid. Independent negative associations were found between serum fT4 levels and global cerebral Aβ deposition after controlling for the effects of age, gender, and the apolipoprotein E ε4 (APOEε4) genotype. Although serum TSH levels were not associated with global cerebral Aβ deposition, they had a significant negative association with glucose metabolism in the precuneus/posterior cingulate cortex after controlling for age, gender, and the APOEε4 genotype. No other thyroid hormones exhibited relationships with either brain Aβ burden or glucose metabolism.ConclusionsEven in a clinical euthyroid state, low serum fT4 and high serum TSH levels appear to be differentially associated with AD-specific brain changes.

Frequency of depression syndromes in elderly individuals with no cognitive disorders, mild cognitive impairment, and Alzheimer’s disease dementia in a memory clinic setting

AIMSnThe aims of this study were to investigate the frequency of various depressive syndromes in elderly individuals with no cognitive impairment (NC), mild cognitive impairment (MCI), and Alzheimers disease dementia (AD) in a memory clinic setting, and then to test whether severe and milder forms of depressive syndromes are differentially associated with the cognitive groups.nnnMETHODSnFor 216 NC, 478 MCI, and 316 AD subjects, we investigated the frequency of depressive syndromes, defined by three different categories: major and minor depressive disorder (MaDD and MiDD) according to the Diagnostic and Statistical Manual of Mental Disorders, 4th edition, as well as depression according to the National Institute of Mental Health provisional diagnostic criteria for depression in Alzheimers disease (NIMH-dAD).nnnRESULTSnThe frequency of MaDD did not show any significant difference among NC, MCI, and AD. In contrast, the frequencies of MiDD and NIMH-dAD were higher than those of MaDD and showed significant group differences with a gradual increase from NC to AD.nnnCONCLUSIONnThe findings suggest that the degenerative process of Alzheimers disease contributes to the occurrence of mild depressive conditions, but not to severe depression.

FUNCTIONAL NEUROANATOMICAL CORRELATES OF THE FRONTAL ASSESSMENT BATTERY PERFORMANCE IN ALZHEIMER'S DISEASE: A FDG-PET STUDY

remained following adjustment for whole-brain rates. In the CSF subset the estimated association betweenWMHand hippocampal atrophy ratewas of a similar magnitude, but was not statistically significant. After adjusting for Ab and tau measures this estimated association reduced, but again was not statistically significant. In AD, there was no evidence of an association betweenWMH and either atrophy rate measure.Conclusions: These results suggest that increased WMH is associated with disproportionately higher hippocampal tissue loss in controls and MCI subjects. In controls this association remained after adjustment for CSF amyloid and tau.