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  • 1
    In: Nutrition and Healthy Aging, IOS Press, Vol. 8, No. 1 ( 2023-08-24), p. 143-156
    Abstract: BACKGROUND: There is evidence that adherence to Mediterranean-like diet reduces cognitive decline and brain atrophy in Alzheimer's disease (AD). However, lengthy dietary assessments, such as food frequency questionnaires (FFQs), discourage more frequent use. OBJECTIVE: Here we aimed to validate a 6-items short questionnaire for a Mediterranean-like diet (6-QMD) and explore its associations with memory performance and hippocampal atrophy in healthy elders and individuals at risk for AD. METHODS: We analyzed 938 participants (N = 234 healthy controls and N = 704 participants with an increased AD risk) from the DZNE-Longitudinal Cognitive Impairment and Dementia Study (DELCODE). The 6-QMD was validated against the Mediterranean Diet (MeDi) score and the Mediterranean-DASH Diet Intervention for Neurodegenerative Delay (MIND) score, both derived from a detailed FFQ. Furthermore, associations between the 6-QMD and memory function as well as hippocampal atrophy were evaluated using linear regressions. RESULTS: The 6-QMD was moderately associated with the FFQ-derived MeDi adherence score (ρ = 0.25, p  〈  0.001) and the MIND score (ρ = 0.37, p=  〈  0.001). Higher fish and olive oil consumption and lower meat and sausage consumption showed significant associations in a linear regression, adjusted for diagnosis, age, sex and education, with memory function (β = 0.1, p = 0.008) and bilateral hippocampal volumes (left: β = 0.15, p  〈  0.001); (right: β = 0.18, p  〈  0.001)). CONCLUSIONS: The 6-QMD is a useful and valid brief tool to assess the adherence to MeDi and MIND diets, capturing associations with memory function and brain atrophy in healthy elders and individuals at increased AD dementia risk, making it a valid alternative in settings with time constraints.
    Type of Medium: Online Resource
    ISSN: 2451-9480 , 2451-9502
    Language: Unknown
    Publisher: IOS Press
    Publication Date: 2023
    detail.hit.zdb_id: 2879828-4
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  • 2
    In: Molecular Psychiatry, Springer Science and Business Media LLC
    Abstract: β-amyloid (Aβ) and tau aggregation as well as neuronal injury and atrophy (ATN) are the major hallmarks of Alzheimer’s disease (AD), and biomarkers for these hallmarks have been linked to neuroinflammation. However, the detailed regional associations of these biomarkers with microglial activation in individual patients remain to be elucidated. We investigated a cohort of 55 patients with AD and primary tauopathies and 10 healthy controls that underwent TSPO-, Aβ-, tau-, and perfusion-surrogate-PET, as well as structural MRI. Z -score deviations for 246 brain regions were calculated and biomarker contributions of Aβ (A), tau (T), perfusion (N1), and gray matter atrophy (N2) to microglial activation (TSPO, I) were calculated for each individual subject. Individual ATN-related microglial activation was correlated with clinical performance and CSF soluble TREM2 (sTREM2) concentrations. In typical and atypical AD, regional tau was stronger and more frequently associated with microglial activation when compared to regional Aβ (AD: β T  = 0.412 ± 0.196 vs. β A  = 0.142 ± 0.123, p   〈  0.001; AD-CBS: β T  = 0.385 ± 0.176 vs. β A  = 0.131 ± 0.186, p  = 0.031). The strong association between regional tau and microglia reproduced well in primary tauopathies (β T  = 0.418 ± 0.154). Stronger individual associations between tau and microglial activation were associated with poorer clinical performance. In patients with 4RT, sTREM2 levels showed a positive association with tau-related microglial activation. Tau pathology has strong regional associations with microglial activation in primary and secondary tauopathies. Tau and Aβ related microglial response indices may serve as a two-dimensional in vivo assessment of neuroinflammation in neurodegenerative diseases.
    Type of Medium: Online Resource
    ISSN: 1359-4184 , 1476-5578
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2023
    detail.hit.zdb_id: 1502531-7
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  • 3
    In: Alzheimer's & Dementia, Wiley, Vol. 17, No. S1 ( 2021-12)
    Abstract: 18‐kDa translocator protein position‐emission‐tomography (TSPO‐PET) imaging emerged for in vivo assessment of neuroinflammation in preclinical and clinical research of Alzheimer’s disease (AD). Higher TSPO‐PET binding as a surrogate of microglial activation in females has been reported for cognitively normal humans (HC), but sex effects have not yet been systematically evaluated in patients with AD. Thus, we aimed to investigate the impact of sex and the body mass index (BMI) on the relationship between β‐amyloid‐accumulation and microglial activation in AD. Method Fifty‐six patients with AD (34 female; BMI 24.9±4.0; age 71.1±7.7 years; 100% Aβ‐positive; MMSE 20.9±5.5) and 13 Aβ‐negative HC (7 female; BMI 24.2±3.3; age 70.6±7.5 years; MMSE 29.0±1.0) underwent TSPO‐PET ( 18 F‐GE‐180) and β‐amyloid‐PET imaging (Aβ‐PET; 18 F‐flutemetamol). The brain was parcellated into 218 cortical regions and standardized‐uptake‐value‐ratios (SUVr, cerebellar reference) were calculated for TSPO‐ and Aβ‐PET. Per AD patient, the averaged regional increase of TSPO‐ and Aβ‐PET SUVr (z‐score) was calculated versus HC. We used the function between regional Aβ‐PET and TSPO‐PET SUVr to determine the Aβ‐plaque dependent microglial response (slope) and the Aβ‐plaque independent microglial response (intercept) at the single patient level (Figure 1). All PET read‐outs were compared between sexes and we tested for a moderation effect of sex on the association between BMI and microglial activation, controlled for age. Result In AD the mean cortical TSPO‐PET z‐score of females (+0.69±0.72) was higher when compared to males (+0.30±0.73; p=0.048; Figure 2), whereas Aβ‐PET z‐scores were similar (female: +4.56±1.76; male: +4.44±2.08). The Aβ‐plaque independent microglial response was stronger in females with AD (intercept: +0.35±0.63) when compared to males (‐0.23±0.71; p=0.0024) whereas the Aβ‐plaque dependent microglial response was indifferent between sexes (Figure 2). BMI and the Aβ‐plaque independent microglial response were significantly associated in females (β=0.35, p=0.043) but not in males (β=‐0.02, p=0.940; BMI*sex interaction: F (3,52) =4.77, p=0.0052; Figure 3). Conclusion Females with AD comprise a higher Aβ‐plaque independent microglia response, whereas the microglial response to fibrillar Aβ is indifferent between sexes. BMI is positively associated with the Aβ‐plaque independent microglia response in females with AD but not in males, indicating that sex and BMI need to be considered when studying neuroinflammation in AD.
    Type of Medium: Online Resource
    ISSN: 1552-5260 , 1552-5279
    URL: Issue
    Language: English
    Publisher: Wiley
    Publication Date: 2021
    detail.hit.zdb_id: 2201940-6
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  • 4
    In: Annals of Neurology, Wiley, Vol. 92, No. 5 ( 2022-11), p. 768-781
    Abstract: Alzheimer disease (AD) is characterized by amyloid β (Aβ) plaques and neurofibrillary tau tangles, but increasing evidence suggests that neuroinflammation also plays a key role, driven by the activation of microglia. Aβ and tau pathology appear to spread along pathways of highly connected brain regions, but it remains elusive whether microglial activation follows a similar distribution pattern. Here, we assess whether connectivity is associated with microglia activation patterns. Methods We included 32 Aβ‐positive early AD subjects (18 women, 14 men) and 18 Aβ‐negative age‐matched healthy controls (10 women, 8 men) from the prospective ActiGliA (Activity of Cerebral Networks, Amyloid and Microglia in Aging and Alzheimer's Disease) study. All participants underwent microglial activation positron emission tomography (PET) with the third‐generation mitochondrial 18 kDa translocator protein (TSPO) ligand [ 18 F]GE‐180 and magnetic resonance imaging (MRI) to measure resting‐state functional and structural connectivity. Results We found that inter‐regional covariance in TSPO‐PET and standardized uptake value ratio was preferentially distributed along functionally highly connected brain regions, with MRI structural connectivity showing a weaker association with microglial activation. AD patients showed increased TSPO‐PET tracer uptake bilaterally in the anterior medial temporal lobe compared to controls, and higher TSPO‐PET uptake was associated with cognitive impairment and dementia severity in a disease stage‐dependent manner. Interpretation Microglial activation distributes preferentially along highly connected brain regions, similar to tau pathology. These findings support the important role of microglia in neurodegeneration, and we speculate that pathology spreads throughout the brain along vulnerable connectivity pathways. ANN NEUROL 2022;92:768–781
    Type of Medium: Online Resource
    ISSN: 0364-5134 , 1531-8249
    URL: Issue
    Language: English
    Publisher: Wiley
    Publication Date: 2022
    detail.hit.zdb_id: 2037912-2
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  • 5
    In: Scientific Reports, Springer Science and Business Media LLC, Vol. 12, No. 1 ( 2022-07-27)
    Abstract: Artificial intelligence (AI) algorithms evaluating [supine] chest radiographs ([S] CXRs) have remarkably increased in number recently. Since training and validation are often performed on subsets of the same overall dataset, external validation is mandatory to reproduce results and reveal potential training errors. We applied a multicohort benchmarking to the publicly accessible (S)CXR analyzing AI algorithm CheXNet, comprising three clinically relevant study cohorts which differ in patient positioning ([S]CXRs), the applied reference standards (CT-/[S] CXR-based) and the possibility to also compare algorithm classification with different medical experts’ reading performance. The study cohorts include [1] a cohort, characterized by 563 CXRs acquired in the emergency unit that were evaluated by 9 readers (radiologists and non-radiologists) in terms of 4 common pathologies, [2] a collection of 6,248 SCXRs annotated by radiologists in terms of pneumothorax presence, its size and presence of inserted thoracic tube material which allowed for subgroup and confounding bias analysis and [3] a cohort consisting of 166 patients with SCXRs that were evaluated by radiologists for underlying causes of basal lung opacities, all of those cases having been correlated to a timely acquired computed tomography scan (SCXR and CT within  〈  90 min). CheXNet non-significantly exceeded the radiology resident (RR) consensus in the detection of suspicious lung nodules (cohort [1], AUC AI/RR: 0.851/0.839, p  = 0.793) and the radiological readers in the detection of basal pneumonia (cohort [3], AUC AI/reader consensus: 0.825/0.782, p  = 0.390) and basal pleural effusion (cohort [3], AUC AI/reader consensus: 0.762/0.710, p  = 0.336) in SCXR, partly with AUC values higher than originally published (“Nodule”: 0.780, “Infiltration”: 0.735, “Effusion”: 0.864). The classifier “Infiltration” turned out to be very dependent on patient positioning (best in CXR, worst in SCXR). The pneumothorax SCXR cohort [2] revealed poor algorithm performance in CXRs without inserted thoracic material and in the detection of small pneumothoraces, which can be explained by a known systematic confounding error in the algorithm training process. The benefit of clinically relevant external validation is demonstrated by the differences in algorithm performance as compared to the original publication. Our multi-cohort benchmarking finally enables the consideration of confounders, different reference standards and patient positioning as well as the AI performance comparison with differentially qualified medical readers.
    Type of Medium: Online Resource
    ISSN: 2045-2322
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2022
    detail.hit.zdb_id: 2615211-3
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  • 6
    In: Investigative Radiology, Ovid Technologies (Wolters Kluwer Health), Vol. 55, No. 12 ( 2020-12), p. 792-798
    Abstract: We hypothesized that published performances of algorithms for artificial intelligence (AI) pneumothorax (PTX) detection in chest radiographs (CXRs) do not sufficiently consider the influence of PTX size and confounding effects caused by thoracic tubes (TTs). Therefore, we established a radiologically annotated benchmarking cohort (n = 6446) allowing for a detailed subgroup analysis. Materials and Methods We retrospectively identified 6434 supine CXRs, among them 1652 PTX-positive cases and 4782 PTX-negative cases. Supine CXRs were radiologically annotated for PTX size, PTX location, and inserted TTs. The diagnostic performances of 2 AI algorithms (“AI_CheXNet” [Rajpurkar et al], “AI_1.5” [Guendel et al] ), both trained on publicly available datasets with labels obtained from automatic report interpretation, were quantified. The algorithms' discriminative power for PTX detection was quantified by the area under the receiver operating characteristics (AUROC), and significance analysis was based on the corresponding 95% confidence interval. A detailed subgroup analysis was performed to quantify the influence of PTX size and the confounding effects caused by inserted TTs. Results Algorithm performance was quantified as follows: overall performance with AUROCs of 0.704 (AI_1.5) / 0.765 (AI_CheXNet) for unilateral PTXs, AUROCs of 0.666 (AI_1.5) / 0.722 (AI_CheXNet) for unilateral PTXs smaller than 1 cm, and AUROCs of 0.735 (AI_1.5) / 0.818 (AI_CheXNet) for unilateral PTXs larger than 2 cm. Subgroup analysis identified TTs to be strong confounders that significantly influence algorithm performance: Discriminative power is completely eliminated by analyzing PTX-positive cases without TTs referenced to control PTX-negative cases with inserted TTs. Contrarily, AUROCs increased up to 0.875 (AI_CheXNet) for large PTX-positive cases with inserted TTs referenced to control cases without TTs. Conclusions Our detailed subgroup analysis demonstrated that the performance of established AI algorithms for PTX detection trained on public datasets strongly depends on PTX size and is significantly biased by confounding image features, such as inserted TTS. Our established, clinically relevant and radiologically annotated benchmarking cohort might be of great benefit for ongoing algorithm development.
    Type of Medium: Online Resource
    ISSN: 1536-0210 , 0020-9996
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2020
    detail.hit.zdb_id: 2041543-6
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  • 7
    In: European Radiology, Springer Science and Business Media LLC, Vol. 31, No. 10 ( 2021-10), p. 7888-7900
    Abstract: Diagnostic accuracy of artificial intelligence (AI) pneumothorax (PTX) detection in chest radiographs (CXR) is limited by the noisy annotation quality of public training data and confounding thoracic tubes (TT). We hypothesize that in-image annotations of the dehiscent visceral pleura for algorithm training boosts algorithm’s performance and suppresses confounders. Methods Our single-center evaluation cohort of 3062 supine CXRs includes 760 PTX-positive cases with radiological annotations of PTX size and inserted TTs. Three step-by-step improved algorithms (differing in algorithm architecture, training data from public datasets/clinical sites, and in-image annotations included in algorithm training) were characterized by area under the receiver operating characteristics (AUROC) in detailed subgroup analyses and referenced to the well-established “CheXNet” algorithm. Results Performances of established algorithms exclusively trained on publicly available data without in-image annotations are limited to AUROCs of 0.778 and strongly biased towards TTs that can completely eliminate algorithm’s discriminative power in individual subgroups. Contrarily, our final “algorithm 2” which was trained on a lower number of images but additionally with in-image annotations of the dehiscent pleura achieved an overall AUROC of 0.877 for unilateral PTX detection with a significantly reduced TT-related confounding bias. Conclusions We demonstrated strong limitations of an established PTX-detecting AI algorithm that can be significantly reduced by designing an AI system capable of learning to both classify and localize PTX. Our results are aimed at drawing attention to the necessity of high-quality in-image localization in training data to reduce the risks of unintentionally biasing the training process of pathology-detecting AI algorithms. Key Points • Established pneumothorax-detecting artificial intelligence algorithms trained on public training data are strongly limited and biased by confounding thoracic tubes. • We used high-quality in-image annotated training data to effectively boost algorithm performance and suppress the impact of confounding thoracic tubes. • Based on our results, we hypothesize that even hidden confounders might be effectively addressed by in-image annotations of pathology-related image features.
    Type of Medium: Online Resource
    ISSN: 0938-7994 , 1432-1084
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2021
    detail.hit.zdb_id: 1472718-3
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