Risks and Prognoses of Alzheimer's Disease and Vascular Dementia in Patients With Insomnia: A Nationwide Population-Based Study

This study aimed to investigate the risk and prognosis of Alzheimer's disease (AD) and vascular dementia (VaD) in patients with insomnia using the National Health Insurance Service database covering the entire population of the Republic of Korea from 2007 to 2014. In total, 2,796,871 patients aged 40 years or older with insomnia were enrolled, and 5,593,742 controls were matched using a Greedy digit match algorithm. Mortality and the rate of admission to a long-term care facility were estimated using multivariable Cox analysis. Of all patients with insomnia, 138,270 (4.94%) and 26,706 (0.96%) were newly diagnosed with AD and VaD, respectively. The incidence rate ratios for AD and VaD were 1.73 and 2.10, respectively, in patients with insomnia compared with those without. Higher mortality rates and long-term care facility admission rates were also observed in patients with dementia in the insomnia group. Known cardiovascular risk factors showed interactions with the effects of insomnia on the risk of AD and VaD. However, the effects of insomnia on the incidence of AD and VaD were consistent between the groups with and without cardiovascular risk factors. Insomnia is a medically modifiable and policy-accessible risk factor and prognostic marker of AD and VaD.ope

A multicenter comparison of [ 18 F]flortaucipir, [ 18 F]RO948, and [ 18 F]MK6240 tau PET tracers to detect a common target ROI for differential diagnosis

Purpose: This study aims to determine whether comparable target regions of interest (ROIs) and cut-offs can be used across [18F]flortaucipir, [18F]RO948, and [18F]MK6240 tau positron emission tomography (PET) tracers for differential diagnosis of Alzheimer's disease (AD) dementia vs either cognitively unimpaired (CU) individuals or non-AD neurodegenerative diseases. Methods: A total of 1755 participants underwent tau PET using either [18F]flortaucipir (n = 975), [18F]RO948 (n = 493), or [18F]MK6240 (n = 287). SUVR values were calculated across four theory-driven ROIs and several tracer-specific data-driven (hierarchical clustering) regions of interest (ROIs). Diagnostic performance and cut-offs for ROIs were determined using receiver operating characteristic analyses and the Youden index, respectively. Results: Comparable diagnostic performance (area under the receiver operating characteristic curve [AUC]) was observed between theory- and data-driven ROIs. The theory-defined temporal meta-ROI generally performed very well for all three tracers (AUCs: 0.926-0.996). An SUVR value of approximately 1.35 was a common threshold when using this ROI. Conclusion: The temporal meta-ROI can be used for differential diagnosis of dementia patients with [18F]flortaucipir, [18F]RO948, and [18F]MK6240 tau PET with high accuracy, and that using very similar cut-offs of around 1.35 SUVR. This ROI/SUVR cut-off can also be applied across tracers to define tau positivity.ope

Glomerular hyperfiltration is associated with dementia: A nationwide population-based study

Background Glomerular hyperfiltration may be a clinical phenotype of endothelial dysfunction. Endothelial dysfunction may cause vascular dementia through the deterioration of cerebral blood flow. We aimed to identify the risk of dementia in people with glomerular hyperfiltration. Methods Using the Korean National Health Information Database, we included subjects aged >= 45 years who underwent national health screening examinations between 2012 and 2015 and who had no previous history of end-stage renal disease or dementia (n = 2,244,582). The primary exposure was glomerular hyperfiltration. We divided the subjects into groups by sex and five-year age intervals and categorized each group into 8 intervals according to estimated glomerular filtration (eGFR). The subjects with an eGFR >= 95th percentile in each group were defined as the hyperfiltration group. The outcomes were development of all types of dementia, Alzheimer's dementia and vascular dementia. Multivariable Cox proportional hazards models were used to analyze the hazard ratios (HRs) for outcomes. Results The Hyperfiltration group showed a higher risk for the development of all types of dementia [adjusted HR 1.09 (95% CI, 1.03-1.15)] and vascular dementia [adjusted HR 1.33 (95% CI, 1.14-1.55)] than the reference group. However, the association between hyperfiltration and Alzheimer's dementia was not statistically significant. Conclusions Glomerular hyperfiltration may be associated with dementia. In this respect, subjects with glomerular hyperfiltration should be monitored more closely for signs and symptoms of dementia.ope

Study on Basic Characteristics of a Coplanar-type Transmission Line Employing Periodic Structure on Si RFIC

In this study, a short-wavelength coplanar-type transmission line employing periodic ground structure (PGS) was developed for application to miniaturized on-chip passive component on Si Radio Frequency Integrated Circuit (RFIC). The transmission line employing PGS showed shorter wavelength and lower characteristic impedance than conventional coplanar-type transmission line. The wavelength of the transmission line employing PGS structure was 57 % of the conventional coplanar-type transmission line on Si substrate. Using the theoretical analysis, basic characteristics of the transmission line employing PGS (e.g., bandwidth, loss, impedance, and resonance characteristics) were also investigated in order to evaluate its suitability for application to a development of miniaturized passive on-chip components on silicon RFIC. According to the results, the bandwidth of the transmission line employing PGS was more than 895 ㎓ as long as T is less than 20 ㎛, and the resonance characteristic was observed in 1239 ㎓, which indicates that the PPGM structure is a promising candidate for application to a development of miniaturized on-chip passive components on Si RFIC.Abstract = 1 제 1 장 연구 배경 및 목적 = 3 제 2 장 종래의 코프레너형 전송선로 구조 = 6 제 3 장 PGS 구조를 가지는 코프레너형 전송선로의 구조 = 8 제 4 장 PGS 구조의 등가회로 해석 및 이론적 특성 고찰 = 11 4.1 이론적 해석 및 대역폭 특성 = 11 4.2 등가회로 해석 및 공진주파수 특성 = 18 제 5 장 PGS 구조를 가지는 코프레너형 전송선로의 설계 및 제작 결과 = 21 5.1 PGS 구조를 가지는 코프레너형 전송선로의 설계 = 21 5.2 PGS 구조를 가지는 코프레너형 전송선로의 제작 = 22 5.3 선로파장 축소 특성 = 23 5.4 유효 유전율 특성 = 26 5.5 선로손실 특성 = 28 5.6 특성 임피던스 특성 = 30 제 6 장 결론 = 33 참고문헌 = 3

Sex-Related Reserve Hypothesis in Alzheimer's Disease: Changes in Cortical Thickness with a Five-Year Longitudinal Follow-Up

Background: Sex effects on the progression of Alzheimer's disease (AD) have received less attention than other demographic factors, including onset age and education. Objective: The aim of this study was to investigate whether sex affected cortical thinning in the disease progression of AD. Methods: We prospectively recruited 36 patients with early-stage AD and 14 people with normal cognition. All subjects were assessed with magnetic resonance imaging at baseline, Year 1, Year 3, and Year 5. We performed cortical thickness analyses using surface-based morphometry on magnetic resonance imaging. Results: Women with AD showed more rapid cortical thinning in the left dorsolateral frontal cortex, left superior temporal gyrus, bilateral temporo-parietal association cortices, bilateral anterior cingulate gyri, bilateral medial frontal cortices, and bilateral occipital cortices over 5 years than men with AD, even though there was no difference in cortical thickness at baseline. In contrast, there were no regions of significantly more rapid atrophy in men with AD. Conclusions: Our findings suggest that women deteriorate faster than men in the progression of AD.ope

PSEN1 variants in Korean patients with clinically suspicious early-onset familial Alzheimer's disease

Pathogenic variants in the PSEN1 gene are known to be the most common cause of early-onset Alzheimer's disease but there are few data on the frequency and spectrum of PSEN1 variants in Korea. In this study, we investigated PSEN1 variants in a consecutive series of clinically suspicious early-onset familial AD (EOFAD) Korean patients and their clinical characteristics and imaging findings. From January 2007 to December 2013, EOFAD patients with very early onset AD (<50 yr), early onset AD (<60 yr) with two or more relatives with AD, and early onset AD (<60 yr) with one or more first-degree relatives with very early onset AD (<50 yr) were enrolled in this study. Sequence analysis of the PSEN1 gene was performed by Sanger sequencing. Neuroimaging data and conventional brain MRIs and FDG-PET and/or [11C] PiB-PET scans were analyzed in patients with PSEN1 variants. Among the 28 patients with EOFAD, six (21.4%, 6/28) patients had pathogenic or likely pathogenic variants in the PSEN1 gene. Two pathogenic variants were p.Glu120Lys and p.Ser170Phe and four likely pathogenic variants were p.Thr119Ile, p.Tyr159Cys, p.Leu282Pro, and p.Ala285Ser. Two patients had variants of unknown significance, p.Tyr389His and p.Tyr389Ser. EOFAD patients with PSEN1 variants showed early AD onset, frequent visuospatial dysfunction, movement disorders, and rapid disease progression. Brain MRIs revealed diffuse cortical atrophy, including parietal lobe atrophy, and/or hippocampal atrophy. FDG-PET scans also revealed significant hypometabolism in the bilateral temporo-parietal regions. Our findings provide insight to better understand the genetic background of Korean EOFAD patients.ope

Transferability of Alzheimer Disease Polygenic Risk Score Across Populations and Its Association With Alzheimer Disease-Related Phenotypes

Importance: Polygenic risk scores (PRSs), which aggregate the genetic effects of single-nucleotide variants identified in genome-wide association studies (GWASs), can help distinguish individuals at a high genetic risk for Alzheimer disease (AD). However, genetic studies have predominantly focused on populations of European ancestry. Objective: To evaluate the transferability of a PRS for AD in the Korean population using summary statistics from a prior GWAS of European populations. Design, setting, and participants: This cohort study developed a PRS based on the summary statistics of a large-scale GWAS of a European population (the International Genomics of Alzheimer Project; 21 982 AD cases and 41 944 controls). This PRS was tested for an association with AD dementia and its related phenotypes in 1634 Korean individuals, who were recruited from 2013 to 2019. The association of a PRS based on a GWAS of a Japanese population (the National Center for Geriatrics and Gerontology; 3962 AD cases and 4074 controls) and a transancestry meta-analysis of European and Japanese GWASs was also evaluated. Data were analyzed from December 2020 to June 2021. Main outcomes and measures: Risk of AD dementia, amnestic mild cognitive impairment (aMCI), earlier symptom onset, and amyloid β deposition (Aβ). Results: A total of 1634 Korean patients (969 women [59.3%]), including 716 individuals (43.6%) with AD dementia, 222 (13.6%) with aMCI, and 699 (42.8%) cognitively unimpaired controls, were analyzed in this study. The mean (SD) age of the participants was 71.6 (9.0) years. Higher PRS was associated with a higher risk of AD dementia independent of APOE ɛ4 status in the Korean population (OR, 1.95; 95% CI, 1.40-2.72; P < .001). Furthermore, PRS was associated with aMCI, earlier symptom onset, and Aβ deposition independent of APOE ɛ4 status. The PRS based on a transancestry meta-analysis of data sets comprising 2 distinct ancestries showed a slightly improved accuracy. Conclusions and relevance: In this cohort study, a PRS derived from a European GWAS identified individuals at a high risk for AD dementia in the Korean population. These findings emphasize the transancestry transferability and clinical value of PRSs and suggest the importance of enriching diversity in genetic studies of AD.ope

Multimodal imaging analyses in patients with genetic and sporadic forms of small vessel disease

Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is thought to be a pure genetic form of subcortical vascular cognitive impairment (SVCI). The aim of this study was to compare white matter integrity and cortical thickness between typical CADASIL, a genetic form, and two sporadic forms of SVCI (with NOTCH3 and without NOTCH3 variants). We enrolled typical CADASIL patients (N = 11) and SVCI patients [with NOTCH3 variants (N = 15), without NOTCH3 variants (N = 101)]. To adjust the age difference, which reflects the known difference in clinical and radiologic courses between typical CADASIL patients and SVCI patients, we constructed a W-score of measurement for diffusion tensor image and cortical thickness. Typical CADASIL patients showed more frequent white matter hyperintensities in the bilateral posterior temporal region compared to SVCI patients (p < 0.001, uncorrected). We found that SVCI patients, regardless of the presence of NOTCH3 variants, showed significantly greater microstructural alterations (W-score, p < 0.05, FWE-corrected) and cortical thinning (W-score, p < 0.05, FDR-corrected) than typical CADASIL patients. In this study, typical CADASIL and SVCI showed distinct anatomic vulnerabilities in the cortical and subcortical structures. However, there was no difference between SVCI with NOTCH3 variants and SVCI without NOTCH3 variants.ope

Statin and Ezetimibe Combination Therapy Decreases Mean Platelet Volume Compared to Statin Monotherapy

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Distribution and clinical impact of apolipoprotein E4 in subjective memory impairment and early mild cognitive impairment

The apolipoprotein E (APOE) e4 allele is the most common genetic variant associated with Alzheimer's disease (AD). We sought to investigate the distribution of APOE genotypes across the full clinical AD spectrum including AD, late-stage amnestic mild cognitive impairment (L-aMCI), early-stage aMCI (E-aMCI), subjective memory impairment (SMI), and controls. We prospectively recruited 713 AD patients, 735 aMCI patients, 575 SMI patients, and 8,260 individuals as controls. The frequency of the APOE e4 allele revealed an ordered fashion in the AD (30.8%), L-aMCI (24.0%), E-aMCI (15.1%), SMI (11.7%), and control (9.1%) groups. APOE e3/e4 and e4/e4 genotype frequencies also appeared in an ordered fashion in the AD group (39.1% of e3/e4 and 10.9% of e4/e4), as well as the L-aMCI (28.3% and 9.4%), E-aMCI (22.3% and 3.7%), SMI (18.3% and 1.9%), and control (15.1% and 0.8%) groups. In the comparisons of APOE e3/e3 vs. e3/e4 genotypes, all patient groups had a higher frequency of APOE e3/e4 relative to the control group. Relative to the SMI and E-aMCI groups, the AD and L-aMCI groups had higher frequency of the APOE e3/e4 genotype, and the AD group had a higher frequency relative to the L-aMCI group. However, there was no significant difference between the E-aMCI and SMI groups. In our longitudinal data, APOE e4 carrier showed a steeper incline slope in a clinical dementia rating sum of boxes (CDR-SB) score than APOE e4 non-carrier in SMI (B = 0.0066, p = 0.0104), E-aMCI (B = 0.0313, p < 0.0001), and L-aMCI (B = 0.0178, p = 0.0007). APOE e4 carrier showed a steeper decline slope in the CDR-SB than APOE e4 non-carrier in AD (B = - 0.0309, p = 0.0003). These findings suggest that E-aMCI and SMI are associated with a similarly increased frequency of the APOE e4 allele compared to controls, suggesting a greater genetic risk for AD and the importance of monitoring the allele more closely.ope