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  • 1
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    Online Resource
    Identifying novel genetic variants for brain amyloid deposition: a genome-wide association study in the Korean population
    Springer Science and Business Media LLC ; 2021
    In:  Alzheimer's Research & Therapy Vol. 13, No. 1 ( 2021-12)
    Details
    In: Alzheimer's Research & Therapy, Springer Science and Business Media LLC, Vol. 13, No. 1 ( 2021-12)
    Abstract: Genome-wide association studies (GWAS) have identified a number of genetic variants for Alzheimer’s disease (AD). However, most GWAS were conducted in individuals of European ancestry, and non-European populations are still underrepresented in genetic discovery efforts. Here, we performed GWAS to identify single nucleotide polymorphisms (SNPs) associated with amyloid β (Aβ) positivity using a large sample of Korean population. Methods One thousand four hundred seventy-four participants of Korean ancestry were recruited from multicenters in South Korea. Discovery dataset consisted of 1190 participants (383 with cognitively unimpaired [CU], 330 with amnestic mild cognitive impairment [aMCI] , and 477 with AD dementia [ADD]) and replication dataset consisted of 284 participants (46 with CU, 167 with aMCI, and 71 with ADD). GWAS was conducted to identify SNPs associated with Aβ positivity (measured by amyloid positron emission tomography). Aβ prediction models were developed using the identified SNPs. Furthermore, bioinformatics analysis was conducted for the identified SNPs. Results In addition to APOE , we identified nine SNPs on chromosome 7, which were associated with a decreased risk of Aβ positivity at a genome-wide suggestive level. Of these nine SNPs, four novel SNPs (rs73375428, rs2903923, rs3828947, and rs11983537) were associated with a decreased risk of Aβ positivity ( p 〈  0.05) in the replication dataset. In a meta-analysis, two SNPs (rs7337542 and rs2903923) reached a genome-wide significant level ( p 〈  5.0 × 10 −8 ). Prediction performance for Aβ positivity increased when rs73375428 were incorporated (area under curve = 0.75; 95% CI = 0.74–0.76) in addition to clinical factors and APOE genotype. Cis-eQTL analysis demonstrated that the rs73375428 was associated with decreased expression levels of FGL2 in the brain. Conclusion The novel genetic variants associated with FGL2 decreased risk of Aβ positivity in the Korean population. This finding may provide a candidate therapeutic target for AD, highlighting the importance of genetic studies in diverse populations.
    Type of Medium: Online Resource
    ISSN: 1758-9193
    URL: Article
    DOI: 10.1186/s13195-021-00854-z
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2021
    detail.hit.zdb_id: 2506521-X
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  • 2
    Online Resource
    Online Resource
    Helicobacter Pylori Infection Is Associated with Neurodegeneration in Cognitively Normal Men
    IOS Press ; 2021
    In:  Journal of Alzheimer's Disease Vol. 82, No. 4 ( 2021-08-17), p. 1591-1599
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    In: Journal of Alzheimer's Disease, IOS Press, Vol. 82, No. 4 ( 2021-08-17), p. 1591-1599
    Abstract: Background: An association between Helicobacter pylori (H. pylori) infection and dementia was reported in previous studies; however, the evidence is inconsistent. Objective: In the present study, the association between H. pylori infection and brain cortical thickness as a biomarker of neurodegeneration was investigated. Methods: A cross-sectional study of 822 men who underwent a medical health check-up, including an esophagogastroduodenoscopy and 3.0 T magnetic resonance imaging, was performed. H. pylori infection status was assessed based on histology. Multiple linear regression analyses were conducted to evaluate the relationship between H. pylori infection and brain cortical thickness. Results: Men with H. pylori infection exhibited overall brain cortical thinning (p = 0.022), especially in the parietal (p = 0.008) and occipital lobes (p = 0.050) compared with non-infected men after adjusting for age, educational level, alcohol intake, smoking status, and intracranial volume. 3-dimentional topographical analysis showed that H. pylori infected men had cortical thinning in the bilateral lateral temporal, lateral frontal, and right occipital areas compared with non-infected men with the same adjustments (false discovery rate corrected, Q  〈  0.050). The association remained significant after further adjusting for inflammatory marker (C-reactive protein) and metabolic factors (obesity, dyslipidemia, fasting glucose, and blood pressure). Conclusion: Our results indicate H. pylori infection is associated with neurodegenerative changes in cognitive normal men. H. pylori infection may play a pathophysiologic role in the neurodegeneration and further studies are needed to validate this association.
    Type of Medium: Online Resource
    ISSN: 1387-2877 , 1875-8908
    URL: Article
    DOI: 10.3233/JAD-210119
    Language: Unknown
    Publisher: IOS Press
    Publication Date: 2021
    detail.hit.zdb_id: 2070772-1
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  • 3
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    Online Resource
    Cognitive trajectories of patients with focal ß-amyloid deposition
    Springer Science and Business Media LLC ; 2021
    In:  Alzheimer's Research & Therapy Vol. 13, No. 1 ( 2021-12)
    Details
    In: Alzheimer's Research & Therapy, Springer Science and Business Media LLC, Vol. 13, No. 1 ( 2021-12)
    Abstract: The presence of ß-amyloid (Aß) in the brain can be identified using amyloid PET. In clinical practice, the amyloid PET is interpreted based on dichotomous visual rating, which renders focal Aß accumulation be read as positive for Aß. However, the prognosis of patients with focal Aß deposition is not well established. Thus, we investigated cognitive trajectories of patients with focal Aß deposition. Methods We followed up 240 participants (112 cognitively unimpaired [CU], 78 amnestic mild cognitive impairment [aMCI] , and 50 Alzheimer’s disease (AD) dementia [ADD]) for 2 years from 9 referral centers in South Korea. Participants were assessed with neuropsychological tests and 18 F-flutemetamol (FMM) positron emission tomography (PET). Ten regions (frontal, precuneus/posterior cingulate (PPC), lateral temporal, parietal, and striatum of each hemisphere) were visually examined in the FMM scan, and participants were divided into three groups: No-FMM, Focal-FMM (FMM uptake in 1–9 regions), and Diffuse-FMM. We used mixed-effects model to investigate the speed of cognitive decline in the Focal-FMM group according to the cognitive level, extent, and location of Aß involvement, in comparison with the No- or Diffuse-FMM group. Results Forty-five of 240 (18.8%) individuals were categorized as Focal-FMM. The rate of cognitive decline in the Focal-FMM group was faster than the No-FMM group (especially in the CU and aMCI stage) and slower than the Diffuse-FMM group (in particular in the CU stage). Within the Focal-FMM group, participants with FMM uptake to a larger extent (7–9 regions) showed faster cognitive decline compared to those with uptake to a smaller extent (1–3 or 4–6 regions). The Focal-FMM group was found to have faster cognitive decline in comparison with the No-FMM when there was uptake in the PPC, striatum, and frontal cortex. Conclusions When predicting cognitive decline of patients with focal Aß deposition, the patients’ cognitive level, extent, and location of the focal involvement are important.
    Type of Medium: Online Resource
    ISSN: 1758-9193
    URL: Article
    DOI: 10.1186/s13195-021-00787-7
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2021
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  • 4
    Online Resource
    Online Resource
    Decreased visual acuity is related to thinner cortex in cognitively normal adults: cross-sectional, single-center cohort study
    Springer Science and Business Media LLC ; 2022
    In:  Alzheimer's Research & Therapy Vol. 14, No. 1 ( 2022-12)
    Details
    In: Alzheimer's Research & Therapy, Springer Science and Business Media LLC, Vol. 14, No. 1 ( 2022-12)
    Abstract: Decreased visual acuity (VA) is reported to be a risk factor for dementia. However, the association between VA and cortical thickness has not been established. We investigated the association between VA and cortical thickness in cognitively normal adults. Method We conducted a cross-sectional, single-center cohort study with cognitively normal adults (aged ≥ 45) who received medical screening examinations at the Health Promotion Center at Samsung Medical Center. Subjects were categorized as bad (VA ≤ 20/40), fair (20/40 〈 VA ≤ 20/25), and good (VA 〉 20/25) VA group by using corrected VA in the Snellen system. Using 3D volumetric brain MRI, cortical thickness was calculated using the Euclidean distance between the linked vertices of the inner and outer surfaces. We analyzed the association between VA and cortical thickness after controlling for age, sex, hypertension, diabetes, dyslipidemia, intracranial volume, and education level. Results A total of 2756 subjects were analyzed in this study. Compared to the good VA group, the bad VA group showed overall thinner cortex ( p = 0.015), especially in the parietal ( p = 0.018) and occipital ( p = 0.011) lobes. Topographical color maps of vertex-wise analysis also showed that the bad VA group showed a thinner cortex in the parieto-temporo-occipital area. These results were more robust in younger adults (aged 45 to 65) as decreased VA was associated with thinner cortex in more widespread regions in the parieto-temporo-occipital area. Conclusion Our results suggest that a thinner cortex in the visual processing area of the brain is related to decreased visual stimuli.
    Type of Medium: Online Resource
    ISSN: 1758-9193
    URL: Article
    DOI: 10.1186/s13195-022-01045-0
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2022
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  • 5
    Online Resource
    Online Resource
    A Case of Early-Onset Alzheimer’s Disease Mimicking Schizophrenia in a Patient with Presenilin 1 Mutation (S170P)
    IOS Press ; 2021
    In:  Journal of Alzheimer's Disease Vol. 83, No. 3 ( 2021-09-28), p. 1025-1031
    Details
    In: Journal of Alzheimer's Disease, IOS Press, Vol. 83, No. 3 ( 2021-09-28), p. 1025-1031
    Abstract: Atypical psychological symptoms frequently occur in early-onset Alzheimer’s disease (EOAD), which makes it difficult to differentiate it from other psychiatric disorders. We report the case of a 28-year-old woman with EOAD, carrying a presenilin-1 mutation (S170P), who was initially misdiagnosed with schizophrenia because of prominent psychiatric symptoms in the first 1–2 years of the disease. Amyloid-β positron emission tomography (PET) showed remarkably high tracer uptake in the striatum and thalamus. Tau PET showed widespread cortical uptake and relatively low uptake in the subcortical and medial temporal regions. Our case advocates for considering EOAD diagnosis for young patients with psychiatric and atypical cognitive symptoms.
    Type of Medium: Online Resource
    ISSN: 1387-2877 , 1875-8908
    URL: Article
    DOI: 10.3233/JAD-210650
    Language: Unknown
    Publisher: IOS Press
    Publication Date: 2021
    detail.hit.zdb_id: 2070772-1
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