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Daniel Janowitz

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3 papers

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YNICL Journal 2026 Journal Article

Additive value of early-phase β-Amyloid-PET for the differential diagnosis of non-Alzheimer’s disease dementia

Sebastian Eckenweber
Friederike Völter
Nicolai Franzmeier
Carla Palleis
Olivia Wagemann
Endy Weidinger
Sabrina Katzdobler
Elisabeth Wlasich

PURPOSE: F]FDG-PET, indicating the potential of early-phase β-amyloid-PET as a surrogate biomarker of neuronal injury. We therefore aimed to investigate the additive value of early-phase β-amyloid-PET for the differential diagnosis of non-Alzheimer's disease dementia syndromes in clinical routine. MATERIALS AND METHODS: F]flutemetamol-PET scans (n = 379) performed between July 2013 and July 2021 were analyzed for their amyloid status and the presence of a neurodegenerative hypoperfusion pattern using visual assessment and z-score maps. In patients visually rated as amyloid-negative/neurodegeneration-positive (A-N+), the most likely diagnosis based on perfusion patterns was compared to the final clinical diagnosis, i.e. frontotemporal dementia or psychiatric disorders, suspected 4R-tauopathy, and suspected non-Alzheimer pathophysiology. Logistic regression models based on a data-driven selection of cerebral regions of hypoperfusion by principal component analysis were used to predict neurodegenerative disease and clinical diagnoses. Diagnostic accuracy was compared between visual assessment and the regression models. RESULTS: Neurodegeneration status was correctly identified in 78.8% (119/151) of amyloid-negative patients through visual rating, compared to 67.5% (102/151) using logistic regression. Visual assessment assigned 75.3% (67/89) of A-N+ patients to the correct diagnostic category. In contrast, the regression model classified 69.7% (62/89) of patients. CONCLUSIONS: The current study demonstrates an additive value of early-phase β-amyloid-PET for the differential diagnosis of dementia syndromes. While visual assessment of early-phase β-amyloid-PET already provides substantial diagnostic accuracy, a data-driven analysis approach could aid in cases of uncertainty.

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YNICL Journal 2021 Journal Article

Association between composite scores of domain-specific cognitive functions and regional patterns of atrophy and functional connectivity in the Alzheimer’s disease spectrum

Chimezie O. Amaefule
Martin Dyrba
Steffen Wolfsgruber
Alexandra Polcher
Anja Schneider
Klaus Fliessbach
Annika Spottke
Dix Meiberth

BACKGROUND: Cognitive decline has been found to be associated with gray matter atrophy and disruption of functional neural networks in Alzheimer's disease (AD) in structural and functional imaging (fMRI) studies. Most previous studies have used single test scores of cognitive performance among monocentric cohorts. However, cognitive domain composite scores could be more reliable than single test scores due to the reduction of measurement error. Adopting a multicentric resting state fMRI (rs-fMRI) and cognitive domain approach, we provide a comprehensive description of the structural and functional correlates of the key cognitive domains of AD. METHOD: We analyzed MRI, rs-fMRI and cognitive domain score data of 490 participants from an interim baseline release of the multicenter DELCODE study cohort, including 54 people with AD, 86 with Mild Cognitive Impairment (MCI), 175 with Subjective Cognitive Decline (SCD), and 175 Healthy Controls (HC) in the AD-spectrum. Resulting cognitive domain composite scores (executive, visuo-spatial, memory, working memory and language) from the DELCODE neuropsychological battery (DELCODE-NP), were previously derived using confirmatory factor analysis. Statistical analyses examined the differences between diagnostic groups, and the association of composite scores with regional atrophy and network-specific functional connectivity among the patient subgroup of SCD, MCI and AD. RESULT: Cognitive performance, atrophy patterns and functional connectivity significantly differed between diagnostic groups in the AD-spectrum. Regional gray matter atrophy was positively associated with visuospatial and other cognitive impairments among the patient subgroup in the AD-spectrum. Except for the visual network, patterns of network-specific resting-state functional connectivity were positively associated with distinct cognitive impairments among the patient subgroup in the AD-spectrum. CONCLUSION: Consistent associations between cognitive domain scores and both regional atrophy and network-specific functional connectivity (except for the visual network), support the utility of a multicentric and cognitive domain approach towards explicating the relationship between imaging markers and cognition in the AD-spectrum.

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YNICL Journal 2020 Journal Article

Multimodal MRI analysis of basal forebrain structure and function across the Alzheimer’s disease spectrum

Meret Herdick
Martin Dyrba
Hans-Christian J. Fritz
Slawek Altenstein
Tommaso Ballarini
Frederic Brosseron
Katharina Buerger
Arda Can Cetindag

BACKGROUND: Dysfunction of the cholinergic basal forebrain (cBF) is associated with cognitive decline in Alzheimer's disease (AD). Multimodal MRI allows for the investigation of cBF changes in-vivo. In this study we assessed alterations in cBF functional connectivity (FC), mean diffusivity (MD), and volume across the spectrum of AD. We further assessed effects of amyloid pathology on these changes. METHODS: Participants included healthy controls, and subjects with subjective cognitive decline (SCD), mild cognitive impairment (MCI), or AD dementia (ADD) from the multicenter DELCODE study. Resting-state functional MRI (rs-fMRI) and structural MRI data was available for 477 subjects, and a subset of 243 subjects also had DTI data available. Differences between diagnostic groups were investigated using seed-based FC, volumetric, and MD analyses of functionally defined anterior (a-cBF) and posterior (p-cBF) subdivisions of a cytoarchitectonic cBF region-of-interest. In complementary analyses groups were stratified according to amyloid status based on CSF Aβ42/40 biomarker data, which was available in a subset of participants. RESULTS: a-cBF and p-cBF subdivisions showed regional FC profiles that were highly consistent with previously reported patterns, but there were only minimal differences between diagnostic groups. Compared to controls, cBF volumes and MD were significantly different in MCI and ADD but not in SCD. The Aβ42/40 stratified analyses largely matched these results. CONCLUSIONS: We reproduced subregion-specific FC profiles of the cBF in a clinical sample spanning the AD spectrum. At least in this multicentric cohort study, cBF-FC did not show marked changes along the AD spectrum, and multimodal MRI did not provide more sensitive measures of AD-related cBF changes compared to volumetry.

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