Publications
282 results found
Hayek D, Ziegler G, Kleineidam L, et al., 2024, Different inflammatory signatures based on CSF biomarkers relate to preserved or diminished brain structure and cognition., Mol Psychiatry
Neuroinflammation is a hallmark of Alzheimer's disease (AD) and both positive and negative associations of individual inflammation-related markers with brain structure and cognitive function have been described. We aimed to identify inflammatory signatures of CSF immune-related markers that relate to changes of brain structure and cognition across the clinical spectrum ranging from normal aging to AD. A panel of 16 inflammatory markers, Aβ42/40 and p-tau181 were measured in CSF at baseline in the DZNE DELCODE cohort (n = 295); a longitudinal observational study focusing on at-risk stages of AD. Volumetric maps of gray and white matter (GM/WM; n = 261) and white matter hyperintensities (WMHs, n = 249) were derived from baseline MRIs. Cognitive decline (n = 204) and the rate of change in GM volume was measured in subjects with at least 3 visits (n = 175). A principal component analysis on the CSF markers revealed four inflammatory components (PCs). Of these, the first component PC1 (highly loading on sTyro3, sAXL, sTREM2, YKL-40, and C1q) was associated with older age and higher p-tau levels, but with less pathological Aβ when controlling for p-tau. PC2 (highly loading on CRP, IL-18, complement factor F/H and C4) was related to male gender, higher body mass index and greater vascular risk. PC1 levels, adjusted for AD markers, were related to higher GM and WM volumes, less WMHs, better baseline memory, and to slower atrophy rates in AD-related areas and less cognitive decline. In contrast, PC2 related to less GM and WM volumes and worse memory at baseline. Similar inflammatory signatures and associations were identified in the independent F.ACE cohort. Our data suggest that there are beneficial and detrimental signatures of inflammatory CSF biomarkers. While higher levels of TAM receptors (sTyro/sAXL) or sTREM2 might reflect a protective glia response to degeneration related to phagocytic c
Palleis C, Franzmeier N, Weidinger E, et al., 2024, Association of Neurofilament Light Chain, [18F]PI-2620 Tau-PET, TSPO-PET, and Clinical Progression in Patients With β-Amyloid-Negative CBS., Neurology, Vol: 102
BACKGROUND AND OBJECTIVES: Corticobasal syndrome (CBS) with underlying 4-repeat tauopathy is a progressive neurodegenerative disease characterized by declining cognitive and motor functions. Biomarkers for assessing pathologic brain changes in CBS including tau-PET, 18 kDa translocator protein (TSPO)-PET, structural MRI, neurofilament light chain (NfL), or glial fibrillary acidic protein (GFAP) have recently been evaluated for differential diagnosis and disease staging, yet their association with disease trajectories remains unclear. Therefore, we performed a head-to-head comparison of neuroimaging (tau-PET, TSPO-PET, structural MRI) and plasma biomarkers (NfL, GFAP) as prognostic tools for longitudinal clinical trajectories in β-amyloid (Aβ)-negative CBS. METHODS: We included patients with clinically diagnosed Aβ-negative CBS with clinical follow-up data who underwent baseline structural MRI and plasma-NfL analysis for assessing neurodegeneration, [18F]PI-2620-PET for assessing tau pathology, [18F]GE-180-PET for assessing microglia activation, and plasma-GFAP analysis for assessing astrocytosis. To quantify tau and microglia load, we assessed summary scores of whole-brain, cortical, and subcortical PET signal. For structural MRI analysis, we quantified subcortical and cortical gray matter volume. Plasma NfL and GFAP values were assessed using Simoa-based immunoassays. Symptom progression was determined using a battery of cognitive and motor tests (i.e., Progressive Supranuclear Palsy Rating Scale [PSPRS]). Using linear mixed models, we tested whether the assessed biomarkers at baseline were associated with faster symptom progression over time (i.e., time × biomarker interaction). RESULTS: Overall, 21 patients with Aβ-negative CBS with ∼2-year clinical follow-up data were included. Patients with CBS with more widespread global tau-PET signal showed faster clinical progression (PSPRS: B/SE = 0.001/0.0005, p = 0.025), driven by cortical r
Stark M, Wolfsgruber S, Kleineidam L, et al., 2023, Relevance of Minor Neuropsychological Deficits in Patients With Subjective Cognitive Decline., Neurology, Vol: 101, Pages: e2185-e2196
BACKGROUND AND OBJECTIVES: To determine the relevance of minor neuropsychological deficits (MNPD) in patients with subjective cognitive decline (SCD) with regard to CSF levels of Alzheimer disease (AD) biomarkers, cognitive decline, and clinical progression to mild cognitive impairment (MCI). METHODS: This study included patients with clinical SCD and SCD-free, healthy control (HC) participants with available baseline CSF and/or longitudinal cognitive data from the observational DZNE Longitudinal Cognitive Impairment and Dementia study. We defined MNPD as a performance of at least 0.5SD below the mean on a demographically adjusted total score derived from the Consortium to Establish a Registry for Alzheimer's Disease neuropsychological assessment battery. We compared SCD patients with MNPD and those without MNPD with regard to CSF amyloid-β (Aβ)42/Aβ40, phosphorylated tau (p-tau181), total tau and Aβ42/p-tau181 levels, longitudinal cognitive composite trajectories, and risk of clinical progression to incident MCI (follow-up M ± SD: 40.6 ± 23.7 months). In addition, we explored group differences between SCD and HC in those without MNPD. RESULTS: In our sample (N = 672, mean age: 70.7 ± 5.9 years, 50% female), SCD patients with MNPD (n = 55, 12.5% of SCD group) showed significantly more abnormal CSF biomarker levels, increased cognitive decline, and a higher risk of progression to incident MCI (HR: 4.07, 95% CI 2.46-6.74) compared with SCD patients without MNPD (n = 384). MNPD had a positive predictive value of 57.0% (95% CI 38.5-75.4) and a negative predictive value of 86.0% (95% CI 81.9-90.1) for the progression of SCD to MCI within 3 years. SCD patients without MNPD showed increased cognitive decline and a higher risk of incident MCI compared with HC participants without MNPD (n = 215; HR: 4.09, 95% CI 2.07-8.09), while AD biomarker levels did not differ significantly between these groups. DISCUSSION: Our results suggest tha
Sadlon A, Takousis P, Ankli B, et al., 2023, Association of Chronic Pain with Biomarkers of Neurodegeneration, Microglial Activation, and Inflammation in Cerebrospinal Fluid and Impaired Cognitive Function, ANNALS OF NEUROLOGY, ISSN: 0364-5134
Waschkies KF, Soch J, Darna M, et al., 2023, Machine learning-based classification of Alzheimer's disease and its at-risk states using personality traits, anxiety, and depression., Int J Geriatr Psychiatry, Vol: 38
BACKGROUND: Alzheimer's disease (AD) is often preceded by stages of cognitive impairment, namely subjective cognitive decline (SCD) and mild cognitive impairment (MCI). While cerebrospinal fluid (CSF) biomarkers are established predictors of AD, other non-invasive candidate predictors include personality traits, anxiety, and depression, among others. These predictors offer non-invasive assessment and exhibit changes during AD development and preclinical stages. METHODS: In a cross-sectional design, we comparatively evaluated the predictive value of personality traits (Big Five), geriatric anxiety and depression scores, resting-state functional magnetic resonance imaging activity of the default mode network, apoliprotein E (ApoE) genotype, and CSF biomarkers (tTau, pTau181, Aβ42/40 ratio) in a multi-class support vector machine classification. Participants included 189 healthy controls (HC), 338 individuals with SCD, 132 with amnestic MCI, and 74 with mild AD from the multicenter DZNE-Longitudinal Cognitive Impairment and Dementia Study (DELCODE). RESULTS: Mean predictive accuracy across all participant groups was highest when utilizing a combination of personality, depression, and anxiety scores. HC were best predicted by a feature set comprised of depression and anxiety scores and participants with AD were best predicted by a feature set containing CSF biomarkers. Classification of participants with SCD or aMCI was near chance level for all assessed feature sets. CONCLUSION: Our results demonstrate predictive value of personality trait and state scores for AD. Importantly, CSF biomarkers, personality, depression, anxiety, and ApoE genotype show complementary value for classification of AD and its at-risk stages.
Perneczky R, Dom G, Chan A, et al., 2023, Anti-amyloid antibody treatments for Alzheimer's disease, EUROPEAN JOURNAL OF NEUROLOGY, ISSN: 1351-5101
Sadlon A, Takousis P, Evangelou E, et al., 2023, Association of Blood MicroRNA Expression and Polymorphisms with Cognitive and Biomarker Changes in Older Adults, JPAD-JOURNAL OF PREVENTION OF ALZHEIMERS DISEASE, ISSN: 2274-5807
Finze A, Biechele G, Rauchmann B-S, et al., 2023, Individual regional associations between Aβ-, tau- and neurodegeneration (ATN) with microglial activation in patients with primary and secondary tauopathies, MOLECULAR PSYCHIATRY, ISSN: 1359-4184
Perna L, Mons U, Stocker H, et al., 2023, High cholesterol levels change the association of biomarkers of neurodegenerative diseases with dementia risk: Findings from a population-based cohort, ALZHEIMERS & DEMENTIA, Vol: 19, Pages: 2913-2922, ISSN: 1552-5260
Nemy M, Dyrba M, Brosseron F, et al., 2023, Cholinergic white matter pathways along the Alzheimer's disease continuum, BRAIN, Vol: 146, Pages: 2075-2088, ISSN: 0006-8950
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- Citations: 3
Jiang X, Hu X, Daamen M, et al., 2023, Altered limbic functional connectivity in individuals with subjective cognitive decline: Converging and diverging findings across Chinese and German cohorts, ALZHEIMERS & DEMENTIA, ISSN: 1552-5260
Kurz C, Stoeckl L, Schrurs I, et al., 2023, Impact of pre-analytical sample handling factors on plasma biomarkers of Alzheimer's disease, JOURNAL OF NEUROCHEMISTRY, Vol: 165, Pages: 95-105, ISSN: 0022-3042
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- Citations: 1
Ballarini T, Kuhn E, Roeske S, et al., 2023, Linking early-life bilingualism and cognitive advantage in older adulthood, NEUROBIOLOGY OF AGING, Vol: 124, Pages: 18-28, ISSN: 0197-4580
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- Citations: 1
Heinzinger N, Maass A, Berron D, et al., 2023, Exploring the ATN classification system using brain morphology, ALZHEIMERS RESEARCH & THERAPY, Vol: 15
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- Citations: 1
Ballweg A, Klaus C, Vogler L, et al., 2023, [<SUP>18</SUP>F]F-DED PET imaging of reactive astrogliosis in neurodegenerative diseases: preclinical proof of concept and first-in-human data, JOURNAL OF NEUROINFLAMMATION, Vol: 20
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- Citations: 1
Potashman M, Pang M, Tahir M, et al., 2023, Psychometric properties of the Alzheimer's Disease Cooperative Study - Activities of Daily Living for Mild Cognitive Impairment (ADCS-MCI-ADL) scale: a post hoc analysis of the ADCS ADC-008 trial, BMC GERIATRICS, Vol: 23
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Perneczky R, Jessen F, Grimmer T, et al., 2023, Anti-amyloid antibody therapies in Alzheimer's disease, BRAIN, Vol: 146, Pages: 842-849, ISSN: 0006-8950
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- Citations: 17
Yildirim Z, Delen F, Berron D, et al., 2023, Brain reserve contributes to distinguishing preclinical Alzheimer's stages 1 and 2, ALZHEIMERS RESEARCH & THERAPY, Vol: 15
Brosseron F, Maass A, Kleineidam L, et al., 2023, Serum IL-6, sAXL, and YKL-40 as systemic correlates of reduced brain structure and function in Alzheimer's disease: results from the DELCODE study, ALZHEIMERS RESEARCH & THERAPY, Vol: 15
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- Citations: 1
Gaubert M, Dell'Orco A, Lange C, et al., 2023, Performance evaluation of automated white matter hyperintensity segmentation algorithms in a multicenter cohort on cognitive impairment and dementia, FRONTIERS IN PSYCHIATRY, Vol: 13, ISSN: 1664-0640
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- Citations: 1
Katzdobler S, Nitschmann A, Barthel H, et al., 2023, Additive value of [<SUP>18</SUP>F]PI-2620 perfusion imaging in progressive supranuclear palsy and corticobasal syndrome, EUROPEAN JOURNAL OF NUCLEAR MEDICINE AND MOLECULAR IMAGING, Vol: 50, Pages: 423-434, ISSN: 1619-7070
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- Citations: 5
Teipel SJ, Dyrba M, Levin F, et al., 2023, Cognitive Trajectories in Preclinical and Prodromal Alzheimer's Disease Related to Amyloid Status and Brain Atrophy: A Bayesian Approach, JOURNAL OF ALZHEIMERS DISEASE REPORTS, Vol: 7, Pages: 1055-1076
Ersoezlue E, Perneczky R, Tato M, et al., 2023, A Residual Marker of Cognitive Reserve Is Associated with Resting-State Intrinsic Functional Connectivity Along the Alzheimer's Disease Continuum, JOURNAL OF ALZHEIMERS DISEASE, Vol: 92, Pages: 925-940, ISSN: 1387-2877
Georgiou EE-Z, Prapiadou S, Thomopoulos V, et al., 2022, Naming ability assessment in neurocognitive disorders: a clinician's perspective, BMC PSYCHIATRY, Vol: 22
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- Citations: 2
Voelter F, Beyer L, Eckenweber F, et al., 2022, Assessment of perfusion deficit with early phases of [<SUP>18</SUP>F]PI-2620 tau-PET versus [<SUP>18</SUP>F]flutemetamol-amyloid-PET recordings, EUROPEAN JOURNAL OF NUCLEAR MEDICINE AND MOLECULAR IMAGING, ISSN: 1619-7070
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- Citations: 1
Takousis P, Devonshire AS, Redshaw N, et al., 2022, A standardised methodology for the extraction and quantification of cell-free DNA in cerebrospinal fluid and application to evaluation of Alzheimer's disease and brain cancers, NEW BIOTECHNOLOGY, Vol: 72, Pages: 97-106, ISSN: 1871-6784
Kleineidam L, Wolfsgruber S, Weyrauch A-S, et al., 2022, Midlife occupational cognitive requirements protect cognitive function in old age by increasing cognitive reserve, FRONTIERS IN PSYCHOLOGY, Vol: 13, ISSN: 1664-1078
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- Citations: 2
Saller T, Hubig L, Seibold H, et al., 2022, Association between post-operative delirium and use of volatile anesthetics in the elderly: A real-world big data approach, JOURNAL OF CLINICAL ANESTHESIA, Vol: 83, ISSN: 0952-8180
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- Citations: 2
Jansen RE, van der Lee SJ, Gomez-Fonseca D, et al., 2022, Genome-wide meta-analysis for Alzheimer's disease cerebrospinal fluid biomarkers, ACTA NEUROPATHOLOGICA, Vol: 144, Pages: 821-842, ISSN: 0001-6322
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- Citations: 17
Rauchmann B-S, Brendel M, Franzmeier N, et al., 2022, Microglial Activation and Connectivity in Alzheimer Disease and Aging, ANNALS OF NEUROLOGY, Vol: 92, Pages: 768-781, ISSN: 0364-5134
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- Citations: 9
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