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  • 1
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    Data_Sheet_1.docx
    Frontiers Media SA ; 2023
    In:  Frontiers in Aging Neuroscience Vol. 15 ( 2023-8-24)
    Details
    In: Frontiers in Aging Neuroscience, Frontiers Media SA, Vol. 15 ( 2023-8-24)
    Abstract: Beta-amyloid (Abeta) and tau protein in cerebrospinal fluid (CSF) are established diagnostic biomarkers for Alzheimer’s disease (AD). However, these biomarkers may not the only ones existing parameters that reflect Alzheimer’s disease neuropathological change. The use of quantitative metabolomics approach could provide novel insights into dementia progression and identify key metabolic alterations in CSF and serum. Methods In the present study, we quantified a set of 45 metabolites in CSF (71 patients) and 27 in serum (76 patients) in patients with mild cognitive impairment (MCI), AD, and controls using nuclear magnetic resonance (NMR)-based metabolomics. Results We found significantly reduced CSF (1.32-fold, p = 0.0195) and serum (1.47-fold, p = 0.0484) levels of the ketone body acetoacetate in AD and MCI patients. Additionally, we found decreased levels (1.20-fold, p = 0.0438) of the branched-chain amino acid (BCAA) valine in the CSF of AD patients with increased valine degradation pathway metabolites (such as 3-hydroxyisobutyrate and α-ketoisovalerate). Moreover, we discovered that CSF 2-hydroxybutyrate is dramatically reduced in the MCI patient group (1.23-fold, p = 0.039). On the other hand, vitamin C (ascorbate) was significantly raised in CSF of these patients ( p = 0.008). We also identified altered CSF protein content, 1,5-anhydrosorbitol and fructose as further metabolic shifts distinguishing AD from MCI. Significantly decreased serum levels of the amino acid ornithine were seen in the AD dementia group when compared to healthy controls (1.36-fold, p = 0.011). When investigating the effect of sex, we found for AD males the sign of decreased 2-hydroxybutyrate and acetoacetate in CSF while for AD females increased serum creatinine was identified. Conclusion Quantitative NMR metabolomics of CSF and serum was able to efficiently identify metabolic changes associated with dementia groups of MCI and AD patients. Further, we showed strong correlations between these changes and well-established metabolomic and clinical indicators like Abeta.
    Type of Medium: Online Resource
    ISSN: 1663-4365
    URL: Article
    URL: Article
    DOI: 10.3389/fnagi.2023.1219718
    DOI: 10.3389/fnagi.2023.1219718.s001
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2023
    detail.hit.zdb_id: 2558898-9
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  • 2
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    Data_Sheet_1.PDF
    Frontiers Media SA ; 2023
    In:  Frontiers in Psychiatry Vol. 13 ( 2023-1-12)
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    In: Frontiers in Psychiatry, Frontiers Media SA, Vol. 13 ( 2023-1-12)
    Abstract: White matter hyperintensities (WMH), a biomarker of small vessel disease, are often found in Alzheimer’s disease (AD) and their advanced detection and quantification can be beneficial for research and clinical applications. To investigate WMH in large-scale multicenter studies on cognitive impairment and AD, appropriate automated WMH segmentation algorithms are required. This study aimed to compare the performance of segmentation tools and provide information on their application in multicenter research. Methods We used a pseudo-randomly selected dataset ( n = 50) from the DZNE-multicenter observational Longitudinal Cognitive Impairment and Dementia Study (DELCODE) that included 3D fluid-attenuated inversion recovery (FLAIR) images from participants across the cognitive continuum. Performances of top-rated algorithms for automated WMH segmentation [Brain Intensity Abnormality Classification Algorithm (BIANCA), lesion segmentation toolbox (LST), lesion growth algorithm (LGA), LST lesion prediction algorithm (LPA), pgs, and sysu_media] were compared to manual reference segmentation (RS). Results Across tools, segmentation performance was moderate for global WMH volume and number of detected lesions. After retraining on a DELCODE subset, the deep learning algorithm sysu_media showed the highest performances with an average Dice’s coefficient of 0.702 (±0.109 SD) for volume and a mean F1-score of 0.642 (±0.109 SD) for the number of lesions. The intra-class correlation was excellent for all algorithms ( & gt;0.9) but BIANCA (0.835). Performance improved with high WMH burden and varied across brain regions. Conclusion To conclude, the deep learning algorithm, when retrained, performed well in the multicenter context. Nevertheless, the performance was close to traditional methods. We provide methodological recommendations for future studies using automated WMH segmentation to quantify and assess WMH along the continuum of cognitive impairment and AD dementia.
    Type of Medium: Online Resource
    ISSN: 1664-0640
    URL: Article
    URL: Article
    DOI: 10.3389/fpsyt.2022.1010273
    DOI: 10.3389/fpsyt.2022.1010273.s001
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2023
    detail.hit.zdb_id: 2564218-2
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  • 3
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    Data_Sheet_1.docx
    Frontiers Media SA ; 2022
    In:  Frontiers in Psychology Vol. 13 ( 2022-8-25)
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    In: Frontiers in Psychology, Frontiers Media SA, Vol. 13 ( 2022-8-25)
    Abstract: Regular musical activity as a complex multimodal lifestyle activity is proposed to be protective against age-related cognitive decline and Alzheimer’s disease. This cross-sectional study investigated the association and interplay between musical instrument playing during life, multi-domain cognitive abilities and brain morphology in older adults (OA) from the DZNE-Longitudinal Cognitive Impairment and Dementia Study (DELCODE) study. Participants reporting having played a musical instrument across three life periods ( n = 70) were compared to controls without a history of musical instrument playing ( n = 70), well-matched for reserve proxies of education, intelligence, socioeconomic status and physical activity. Participants with musical activity outperformed controls in global cognition, working memory, executive functions, language, and visuospatial abilities, with no effects seen for learning and memory. The musically active group had greater gray matter volume in the somatosensory area, but did not differ from controls in higher-order frontal, temporal, or hippocampal volumes. However, the association between gray matter volume in distributed frontal-to-temporal regions and cognitive abilities was enhanced in participants with musical activity compared to controls. We show that playing a musical instrument during life relates to better late-life cognitive abilities and greater brain capacities in OA. Musical activity may serve as a multimodal enrichment strategy that could help preserve cognitive and brain health in late life. Longitudinal and interventional studies are needed to support this notion.
    Type of Medium: Online Resource
    ISSN: 1664-1078
    URL: Article
    URL: Article
    DOI: 10.3389/fpsyg.2022.945709
    DOI: 10.3389/fpsyg.2022.945709.s001
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2022
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  • 4
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    Data_Sheet_1.pdf
    Frontiers Media SA ; 2022
    In:  Frontiers in Neuroscience Vol. 16 ( 2022-4-19)
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    In: Frontiers in Neuroscience, Frontiers Media SA, Vol. 16 ( 2022-4-19)
    Abstract: Changes in intestinal microbiome composition have been described in animal models of Alzheimer’s disease (AD) and AD patients. Here we investigated how well taxonomic and functional intestinal microbiome data and their combination with clinical data can be used to discriminate between amyloid-positive AD patients and cognitively healthy elderly controls. Methods In the present study we investigated intestinal microbiome in 75 amyloid-positive AD patients and 100 cognitively healthy controls participating in the AlzBiom study. We randomly split the data into a training and a validation set. Intestinal microbiome was measured using shotgun metagenomics. Receiver operating characteristic (ROC) curve analysis was performed to examine the discriminatory ability of intestinal microbiome among diagnostic groups. Results The best model for discrimination of amyloid-positive AD patients from healthy controls with taxonomic data was obtained analyzing 18 genera features, and yielded an area under the receiver operating characteristic curve (AUROC) of 0.76 in the training set and 0.61 in the validation set. The best models with functional data were obtained analyzing 17 GO (Gene Ontology) features with an AUROC of 0.81 in the training set and 0.75 in the validation set and 26 KO [Kyoto Encyclopedia of Genes and Genomes (KEGG) ortholog] features with an AUROC of 0.83 and 0.77, respectively. Using ensemble learning for these three models including a clinical model with the 4 parameters age, gender, BMI and ApoE yielded an AUROC of 0.92 in the training set and 0.80 in the validation set. Discussion In conclusion, we identified a specific Alzheimer signature in intestinal microbiome that can be used to discriminate amyloid-positive AD patients from healthy controls. The diagnostic accuracy increases from taxonomic to functional data and is even better when combining taxonomic, functional and clinical models. Intestinal microbiome represents an innovative diagnostic supplement and a promising area for developing novel interventions against AD.
    Type of Medium: Online Resource
    ISSN: 1662-453X
    URL: Article
    URL: Article
    DOI: 10.3389/fnins.2022.792996
    DOI: 10.3389/fnins.2022.792996.s001
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2022
    detail.hit.zdb_id: 2411902-7
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  • 5
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    Increased Diagnostic Accuracy of Digital vs. Conventional Clock Drawing Test for Discrimination of Patients in the Early Course of Alzheimer’s Disease from Cognitively Healthy Individuals
    Frontiers Media SA ; 2017
    In:  Frontiers in Aging Neuroscience Vol. 9 ( 2017-04-11)
    Details
    In: Frontiers in Aging Neuroscience, Frontiers Media SA, Vol. 9 ( 2017-04-11)
    Type of Medium: Online Resource
    ISSN: 1663-4365
    URL: Article
    DOI: 10.3389/fnagi.2017.00101
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2017
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  • 6
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    Hippocampal and Hippocampal-Subfield Volumes From Early-Onset Major Depression and Bipolar Disorder to Cognitive Decline
    Frontiers Media SA ; 2021
    In:  Frontiers in Aging Neuroscience Vol. 13 ( 2021-4-21)
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    In: Frontiers in Aging Neuroscience, Frontiers Media SA, Vol. 13 ( 2021-4-21)
    Abstract: Background: The hippocampus and its subfields (HippSub) are reported to be diminished in patients with Alzheimer's disease (AD), bipolar disorder (BD), and major depressive disorder (MDD). We examined these groups vs healthy controls (HC) to reveal HippSub alterations between diseases. Methods: We segmented 3T-MRI T2-weighted hippocampal images of 67 HC, 58 BD, and MDD patients from the AFFDIS study and 137 patients from the DELCODE study assessing cognitive decline, including subjective cognitive decline (SCD), amnestic mild cognitive impairment (aMCI), and AD, via Free Surfer 6.0 to compare volumes across groups. Results: Groups differed significantly in several HippSub volumes, particularly between patients with AD and mood disorders. In comparison to HC, significant lower volumes appear in aMCI and AD groups in specific subfields. Smaller volumes in the left presubiculum are detected in aMCI and AD patients, differing from the BD group. A significant linear regression is seen between left hippocampus volume and duration since the first depressive episode. Conclusions: HippSub volume alterations were observed in AD, but not in early-onset MDD and BD, reinforcing the notion of different neural mechanisms in hippocampal degeneration. Moreover, duration since the first depressive episode was a relevant factor explaining the lower left hippocampal volumes present in groups.
    Type of Medium: Online Resource
    ISSN: 1663-4365
    URL: Article
    DOI: 10.3389/fnagi.2021.626974
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2021
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  • 7
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    Data_Sheet_1.pdf
    Frontiers Media SA ; 2022
    In:  Frontiers in Psychology Vol. 13 ( 2022-12-8)
    Details
    In: Frontiers in Psychology, Frontiers Media SA, Vol. 13 ( 2022-12-8)
    Abstract: Several lifestyle factors promote protection against Alzheimer's disease (AD) throughout a person's lifespan. Although such protective effects have been described for occupational cognitive requirements (OCR) in midlife, it is currently unknown whether they are conveyed by brain maintenance (BM), brain reserve (BR), or cognitive reserve (CR) or a combination of them. Methods We systematically derived hypotheses for these resilience concepts and tested them in the population-based AgeCoDe cohort and memory clinic-based AD high-risk DELCODE study. The OCR score (OCRS) was measured using job activities based on the O*NET occupational classification system. Four sets of analyses were conducted: (1) the interaction of OCR and APOE-ε4 with regard to cognitive decline (N = 2,369, AgeCoDe), (2) association with differentially shaped retrospective trajectories before the onset of dementia of the Alzheimer's type (DAT; N = 474, AgeCoDe), (3) cross-sectional interaction of the OCR and cerebrospinal fluid (CSF) AD biomarkers and brain structural measures regarding memory function (N = 873, DELCODE), and (4) cross-sectional and longitudinal association of OCR with CSF AD biomarkers and brain structural measures (N = 873, DELCODE). Results Regarding (1), higher OCRS was associated with a reduced association of APOE-ε4 with cognitive decline (mean follow-up = 6.03 years), consistent with CR and BR. Regarding (2), high OCRS was associated with a later onset but subsequently stronger cognitive decline in individuals converting to DAT, consistent with CR. Regarding (3), higher OCRS was associated with a weaker association of the CSF Aβ42/40 ratio and hippocampal volume with memory function, consistent with CR. Regarding (4), OCR was not associated with the levels or changes in CSF AD biomarkers (mean follow-up = 2.61 years). We found a cross-sectional, age-independent association of OCRS with some MRI markers, but no association with 1-year-change. OCR was not associated with the intracranial volume. These results are not completely consistent with those of BR or BM. Discussion Our results support the link between OCR and CR. Promoting and seeking complex and stimulating work conditions in midlife could therefore contribute to increased resistance to pathologies in old age and might complement prevention measures aimed at reducing pathology.
    Type of Medium: Online Resource
    ISSN: 1664-1078
    URL: Article
    URL: Article
    DOI: 10.3389/fpsyg.2022.957308
    DOI: 10.3389/fpsyg.2022.957308.s001
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2022
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  • 8
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    Data_Sheet_1.docx
    Frontiers Media SA ; 2023
    In:  Frontiers in Aging Neuroscience Vol. 15 ( 2023-8-28)
    Details
    In: Frontiers in Aging Neuroscience, Frontiers Media SA, Vol. 15 ( 2023-8-28)
    Abstract: Sustained environmental enrichment (EE) through a variety of leisure activities may decrease the risk of developing Alzheimer’s disease. This cross-sectional cohort study investigated the association between long-term EE in young adulthood through middle life and microstructure of fiber tracts associated with the memory system in older adults. Methods N = 201 cognitively unimpaired participants (≥ 60 years of age) from the DZNE-Longitudinal Cognitive Impairment and Dementia Study (DELCODE) baseline cohort were included. Two groups of participants with higher ( n = 104) or lower ( n = 97) long-term EE were identified, using the self-reported frequency of diverse physical, intellectual, and social leisure activities between the ages 13 to 65. White matter (WM) microstructure was measured by fractional anisotropy (FA) and mean diffusivity (MD) in the fornix, uncinate fasciculus, and parahippocampal cingulum using diffusion tensor imaging. Long-term EE groups (lower/higher) were compared with adjustment for potential confounders, such as education, crystallized intelligence, and socio-economic status. Results Reported participation in higher long-term EE was associated with greater fornix microstructure, as indicated by higher FA (standardized β = 0.117, p = 0.033) and lower MD (β = −0.147, p = 0.015). Greater fornix microstructure was indirectly associated (FA: unstandardized B = 0.619, p = 0.038; MD: B = −0.035, p = 0.026) with better memory function through higher long-term EE. No significant effects were found for the other WM tracts. Conclusion Our findings suggest that sustained participation in a greater variety of leisure activities relates to preserved WM microstructure in the memory system in older adults. This could be facilitated by the multimodal stimulation associated with the engagement in a physically, intellectually, and socially enriched lifestyle. Longitudinal studies will be needed to support this assumption.
    Type of Medium: Online Resource
    ISSN: 1663-4365
    URL: Article
    URL: Article
    DOI: 10.3389/fnagi.2023.1170879
    DOI: 10.3389/fnagi.2023.1170879.s001
    Language: Unknown
    Publisher: Frontiers Media SA
    Publication Date: 2023
    detail.hit.zdb_id: 2558898-9
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