%0 Journal Article %J J Alzheimers Dis %D 2018 %T The Impact of APOE ɛ4 in Alzheimer's Disease Differs According to Age. %A Kim, Jaeho %A Park, Seongbeom %A Yoo, Heejin %A Jang, Hyemin %A Kim, Yeshin %A Kim, Ko Woon %A Jang, Young Kyoung %A Lee, Jin San %A Kim, Sung Tae %A Kim, Seonwoo %A Lee, Jong Min %A Ki, Chang-Seok %A Na, Duk L %A Seo, Sang Won %A Kim, Hee Jin %K Age Factors %K Aged %K Alzheimer Disease %K Apolipoprotein E4 %K Atrophy %K Brain %K Case-Control Studies %K Cognition %K Female %K Heterozygote %K Humans %K Magnetic Resonance Imaging %K Male %K Memory %K Middle Aged %K Republic of Korea %X

We evaluated how the impact of apolipoprotein E4 (APOE4) differs according to age in Alzheimer's disease (AD) patients. We recruited 846 AD patients and 815 cognitively normal controls and categorized into three groups with respect to their age (<65, 65-74, and ≥75 years). We evaluated the risk of AD in APOE4 carriers and compared cortical thickness and cognitive function according to APOE4 status in each age group. At the point of this study, in young (<65 years) AD, APOE4 noncarriers had the most severe frontal and perisylvian atrophy, while in old (≥75 years) AD, APOE4 carriers had the most severe medial temporal atrophy. In AD under 75 years, APOE4 noncarriers and heterozygotes showed worse performance in language, visuospatial, and frontal function compared to homozygotes, while, in old (≥75 years) AD, APOE4 homozygotes showed worse performance in memory compared to noncarriers. As the detrimental effects of APOE4 seen in older AD patients were not found in younger AD patients, we suggest that some unrevealed factors are associated with cortical atrophy and non-amnestic cognitive dysfunction in young AD with APOE4 noncarriers.

%B J Alzheimers Dis %V 61 %P 1377-1385 %8 2018 %G eng %N 4 %1 http://www.ncbi.nlm.nih.gov/pubmed/29376853?dopt=Abstract %R 10.3233/JAD-170556 %0 Journal Article %J J Alzheimers Dis %D 2017 %T 18F-AV-1451 PET Imaging in Three Patients with Probable Cerebral Amyloid Angiopathy. %A Kim, Hee Jin %A Cho, Hanna %A Werring, David J %A Jang, Young Kyoung %A Kim, Yeo Jin %A Lee, Jin San %A Lee, Juyoun %A Jun, Soomin %A Park, Seongbeom %A Ryu, Young Hoon %A Choi, Jae Yong %A Cho, Young Seok %A Moon, Seung Hwan %A Na, Duk L %A Lyoo, Chul Hyoung %A Seo, Sang Won %K Aged %K Aged, 80 and over %K Aniline Compounds %K Brain %K Carbolines %K Cerebral Amyloid Angiopathy %K Female %K Humans %K Image Processing, Computer-Assisted %K Male %K Positron-Emission Tomography %K Thiazoles %X

Cerebrovascular deposition of amyloid-β, known as cerebral amyloid angiopathy (CAA), is associated with MRI findings of lobar hemorrhage, cerebral microbleeds, and cortical superficial siderosis. Although pathological studies suggest that tau may co-localize with vascular amyloid, this has not yet been investigated in CAA in vivo. Three patients with probable CAA underwent 11C-Pittsburgh Compound B (PiB) PET or 18F-florbetaben PET to evaluate amyloid burden, and 18F-AV-1451 PET to evaluate paired helical filament tau burden. Regions that had cerebral microbleeds or cortical superficial siderosis largely overlapped with those showing increased 18F-AV-1451. Our preliminary study raised the possibility that lobar cerebral microbleeds, and cortical superficial siderosis, which are characteristic markers of vascular amyloid, may be associated with local production of paired helical filament tau.

%B J Alzheimers Dis %V 57 %P 711-716 %8 2017 %G eng %N 3 %1 http://www.ncbi.nlm.nih.gov/pubmed/28282808?dopt=Abstract %R 10.3233/JAD-161139 %0 Journal Article %J J Alzheimers Dis %D 2016 %T Distinctive Resting State Network Disruptions Among Alzheimer's Disease, Subcortical Vascular Dementia, and Mixed Dementia Patients. %A Kim, Hee Jin %A Cha, Jungho %A Lee, Jong-Min %A Shin, Ji Soo %A Jung, Na-Yeon %A Kim, Yeo Jin %A Choe, Yearn Seong %A Lee, Kyung Han %A Kim, Sung Tae %A Kim, Jae Seung %A Lee, Jae Hong %A Na, Duk L %A Seo, Sang Won %K Aged %K Aged, 80 and over %K Alzheimer Disease %K Aniline Compounds %K Cerebral Cortex %K Cross-Sectional Studies %K Dementia %K Dementia, Vascular %K Female %K Humans %K Image Processing, Computer-Assisted %K Male %K Middle Aged %K Models, Neurological %K Neural Pathways %K Neuropsychological Tests %K Oxygen %K Psychiatric Status Rating Scales %K Radionuclide Imaging %K Rest %K Thiazoles %X

BACKGROUND: Recent advances in resting-state functional MRI have revealed altered functional networks in Alzheimer's disease (AD), especially those of the default mode network (DMN) and central executive network (CEN). However, few studies have evaluated whether small vessel disease (SVD) or combined amyloid and SVD burdens affect the DMN or CEN.

OBJECTIVE: The aim of this study was to evaluate whether SVD or combined amyloid and SVD burdens affect the DMN or CEN.

METHODS: In this cross-sectional study, we investigated the resting-state functional connectivity within DMN and CEN in 37 Pittsburgh compound-B (PiB)(+) AD, 37 PiB(-) subcortical vascular dementia (SVaD), 13 mixed dementia patients, and 65 normal controls.

RESULTS: When the resting-state DMN of PiB(+) AD and PiB(-) SVaD patients were compared, the PiB(+) AD patients displayed lower functional connectivity in the inferior parietal lobule while the PiB(-) SVaD patients displayed lower functional connectivity in the medial frontal and superior frontal gyri. Compared to the PiB(-) SVaD or PiB(+) AD, the mixed dementia patients displayed lower functional connectivity within the DMN in the posterior cingulate gyrus. When the resting-state CEN connectivity of PiB(+) AD and PiB(-) SVaD patients were compared, the PiB(-) SVaD patients displayed lower functional connectivity in the anterior insular region. Compared to the PiB(-) SVaD or PiB(+) AD, the mixed dementia patients displayed lower functional connectivity within the CEN in the inferior frontal gyrus.

CONCLUSIONS: Our findings suggest that in PiB(+) AD and PiB(-) SVaD, there is divergent disruptions in resting-state DMN and CEN. Furthermore, patients with combined amyloid and SVD burdens exhibited more disrupted resting-state DMN and CEN than patients with only amyloid or SVD burden.

%B J Alzheimers Dis %V 50 %P 709-18 %8 2016 %G eng %N 3 %1 http://www.ncbi.nlm.nih.gov/pubmed/26757039?dopt=Abstract %R 10.3233/JAD-150637 %0 Journal Article %J J Alzheimers Dis %D 2016 %T Tract-Specific Correlates of Neuropsychological Deficits in Patients with Subcortical Vascular Cognitive Impairment. %A Jung, Na-Yeon %A Han, Cheol E %A Kim, Hee Jin %A Yoo, Sang Wook %A Kim, Hee-Jong %A Kim, Eun-Joo %A Na, Duk L %A Lockhart, Samuel N %A Jagust, William J %A Seong, Joon-Kyung %A Seo, Sang Won %K Aged %K Brain %K Cerebrovascular Disorders %K Cognitive Dysfunction %K Diffusion Magnetic Resonance Imaging %K Diffusion Tensor Imaging %K Female %K Gray Matter %K Humans %K Male %K Neural Pathways %K Neuropsychological Tests %K White Matter %X

The white matter tract-specific correlates of neuropsychological deficits are not fully established in patients with subcortical vascular cognitive impairment (SVCI), where white matter tract damage may be a critical factor in cognitive impairment. The purpose of this study is to investigate the tract-specific correlates of neuropsychological deficits in SVCI patients using tract-specific statistical analysis (TSSA). We prospectively recruited 114 SVCI patients, and 55 age-, gender-, and education-matched individuals with normal cognition (NC). All participants underwent diffusion weighted imaging and neuropsychological testing. We classified tractography results into fourteen major fiber tracts and analyzed group comparison and correlation with cognitive impairments. Relative to NC subjects, SVCI patients showed decreased fractional anisotropy values in bilateral anterior-thalamic radiation, cingulum, superior-longitudinal fasciculus, uncinate fasciculus, corticospinal tract, and left inferior-longitudinal fasciculus. Focal disruptions in specific tracts were associated with specific cognitive impairments. Our findings suggest that disconnection of specific white matter tracts, especially those neighboring and providing connections between gray matter regions important to certain cognitive functions, may contribute to specific cognitive impairments in SVCI.

%B J Alzheimers Dis %V 50 %P 1125-35 %8 2016 %G eng %N 4 %1 http://www.ncbi.nlm.nih.gov/pubmed/26836179?dopt=Abstract %R 10.3233/JAD-150841 %0 Journal Article %J J Alzheimers Dis %D 2016 %T Unstable Body Mass Index and Progression to Probable Alzheimer's Disease Dementia in Patients with Amnestic Mild Cognitive Impairment. %A Ye, Byoung Seok %A Jang, Eun Young %A Kim, Seong Yoon %A Kim, Eun-Joo %A Park, Sun Ah %A Lee, Yunhwan %A Hong, Chang Hyung %A Choi, Seong Hye %A Yoon, Bora %A Yoon, Soo Jin %A Na, Hae Ri %A Lee, Jae-Hong %A Jeong, Jee H %A Kim, Hee Jin %A Na, Duk L %A Seo, Sang Won %K Aged %K Aged, 80 and over %K Alzheimer Disease %K Analysis of Variance %K Body Mass Index %K Body Weight %K Cognitive Dysfunction %K Dementia %K Disease Progression %K Female %K Humans %K Kaplan-Meier Estimate %K Longitudinal Studies %K Male %K Neuropsychological Tests %K Registries %X

BACKGROUND AND OBJECTIVE: We investigated the influence of body mass index (BMI) status at baseline and changes in BMI over a follow-up period on the development of dementia in amnestic mild cognitive impairment (aMCI) patients.

METHODS: The longitudinal data of 747 aMCI patients were used to investigate the relationships among baseline BMI status, subsequent changes in BMI (median follow-up duration: 1.6 years, interquartile range: 1.0-2.3 years), and risk of progression to probable Alzheimer's disease dementia (pADD). The aMCI patients were classified into underweight, normal weight, overweight, and obese subgroups, and further categorized into increased BMI, stable BMI, and decreased BMI subgroups during follow-up using a 4% mean annual change in BMI cut-off value.

RESULTS: Compared to the normal weight group, the underweight group had a higher risk of pADD (hazard ratio [HR]: 1.89, 95% confidence interval [CI]: 1.07-3.37) while the obese group had a lower risk (HR: 0.70, 95% CI: 0.49-0.999). After controllingfor baseline BMI status, the decreased BMI (HR: 2.29, 95% CI: 1.41-3.72) and increased BMI (HR: 3.96, 95% CI: 2.62-6.00) groups were at increased risk of progression to pADD.

CONCLUSIONS: Our findings suggested that underweight at baseline was associated with a higher risk of progression to pADD, while obesity at baseline predicted a lower risk. Furthermore, significant changes in BMI during the follow-up period reflected an increased risk of progression to pADD, regardless of BMI status at baseline.

%B J Alzheimers Dis %V 49 %P 483-91 %8 2016 %G eng %N 2 %1 http://www.ncbi.nlm.nih.gov/pubmed/26484923?dopt=Abstract %R 10.3233/JAD-150556