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Robert Perneczky

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8 papers

1 author row

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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YNIMG Journal 2025 Journal Article

Pragmatic algorithm for visual assessment of 4-Repeat tauopathies in [18F]PI-2620 PET Scans

Theresa Bauer
Matthias Brendel
Mirlind Zaganjori
Alexander M. Bernhardt
Alexander Jäck
Sophia Stöcklein
Maximilian Scheifele
Johannes Levin

AIM: F]PI-2620 images for diagnosing 4R-tauopathies and to develop a straight-forward reading algorithm to improve objectivity and data reproducibility. METHODS: F]PI-2620 PET scans were included. Participants were classified as probable 4R-tauopathies (n = 29), Alzheimer's disease (AD) (n = 20), α-synucleinopathies (n = 15), and healthy controls (n = 19) based on clinical criteria. Visual assessment of tau-PET scans (choice: 4R-tauopathy, AD-tauopathy, no-tauopathy) was conducted using either 20-40-minute or 40-60-minute intervals, with raw (common) and cerebellar grey matter scaled standardized reading settings (intensity-scaled). Two readers evaluated scans independently and blinded, with a third reader providing consensus in case of discrepant primary evaluation. A regional analysis was performed using the cortex, basal ganglia, midbrain, and dentate nucleus. Sensitivity, specificity, and interrater agreement were calculated for all settings and compared against the visual reads of parametric images (0-60-minutes, distribution volume ratios, DVR). RESULTS: Patients with 4R-tauopathies in contrast to non-4R-tauopathies were detected at higher sensitivity in the 20-40-minute frame (common: 79%, scaled: 76%) compared to the 40-60-minute frame (common: 55%, scaled: 62%), albeit with reduced specificity in the common setting (20-40-min: 78%, 40-60-min: 95%), which was ameliorated in the intensity-scaled setting (20-40-min: 91%, 40-60-min: 96%). Combined assessment of multiple brain regions did not significantly improve diagnostic sensitivity, compared to assessing the basal ganglia alone (76% each). Evaluation of intensity-scaled parametric images resulted in higher sensitivity compared to intensity-scaled static scans (86% vs. 76%) at similar specificity (89% vs. 91%). CONCLUSION: F]PI-2620 tau-PET scans demonstrated reliable detection of 4R-tauopathies, particularly when standardized processing methods and early imaging windows were employed. Parametric images should be preferred for visual assessment of 4R-tauopathies.

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YNICL Journal 2021 Journal Article

Cognitive reserve hypothesis in frontotemporal dementia: A FDG-PET study

Leonie Beyer
Johanna Meyer-Wilmes
Sonja Schönecker
Jonas Schnabel
Julia Sauerbeck
Maximilian Scheifele
Catharina Prix
Marcus Unterrainer

BACKGROUND AND OBJECTIVE: F]-fluorodeoxyglucose positron-emission-tomography (FDG-PET) hypometabolism in FTD. METHODS: Sixty-six FTD subjects (age 67 ± 8 years) and twenty-four cognitively healthy controls (HC) were evaluated. Brain regions with FTD-related glucose hypometabolism in the contrast against HC and brain regions that correlate with the cognitive function were defined by a voxel-based analysis and individual FDG-PET values were extracted from all frontotemporal brain areas. Linear regression analysis served to test if education is associated with residualized cognitive performance and regional FDG-PET hypometabolism after controlling for global cognition. RESULTS: Compared to healthy controls, patients with FTD showed glucose hypometabolism in bilateral frontal and temporal brain areas whereas cognition was only associated with deteriorated glucose metabolism in the left temporal lobe. The education level was significantly correlated with the residualized cognitive performance (residuals from regression analysis between hypometabolism and cognitive function as a quantitative index of reserve) and also negatively correlated with left temporal FDG-PET hypometabolism after controlling for cognition. CONCLUSIONS: In patients with FTD, the education level predicts the existing left temporal FDG-PET hypometabolism at the same cognition level, supporting the cognitive reserve hypothesis in FTD.

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YNICL Journal 2019 Journal Article

Neuronal injury biomarkers for assessment of the individual cognitive reserve in clinically suspected Alzheimer's disease

Leonie Beyer
Jonas Schnabel
Philipp Kazmierczak
Michael Ewers
Sonja Schönecker
Catharina Prix
Johanna Meyer-Wilmes
Marcus Unterrainer

OBJECTIVES: ), all according to the A/T/N-classification. The aim of this study was to calculate residual cognitive performance based on neuronal injury biomarkers as a surrogate of cognitive reserve, and to test the predictive value of this index for the individual clinical course. METHODS: . All neuronal injury markers were tested for an association with clinical MMSE and the resulting residuals were correlated with years of education. We used multiple regression analysis to calculate the expected MMSE score based on neuronal injury biomarkers and covariates. The residuals of the partial correlation for each biomarker and the predicted residualized memory function were correlated with individual cognitive changes measured during clinical follow-up (27 ± 13 months). RESULTS: (R = -0.12, p = .22) showed only weak correlations. Residuals of all neuronal injury biomarker regressions correlated significantly with education level, indicating them to be surrogates of cognitive reserve. A positive residual was associated with faster cognitive deterioration at follow-up for the residuals of stand-alone FDG-PET (R = -0.36, p = .01) and the combined residualized memory function model (R = -0.35, p = .02). CONCLUSIONS: These findings suggest that subjects with higher cognitive reserve had accumulated more pathology, which subsequently caused a faster cognitive decline over time. Together with previous findings suggesting that higher reserve is associated with slower cognitive decline, we propose a biphasic reserve effect, with an initially protective phase followed by more rapid decompensation once the protection is overwhelmed.

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YNICL Journal 2014 Journal Article

LRP-1 polymorphism is associated with global and regional amyloid load in Alzheimer's disease in humans in-vivo

Timo Grimmer
Oliver Goldhardt
Liang-Hao Guo
Behrooz H. Yousefi
Stefan Förster
Alexander Drzezga
Christian Sorg
Panagiotis Alexopoulos

OBJECTIVE: Impaired amyloid clearance has been proposed to contribute to β-amyloid deposition in sporadic late-onset Alzheimer's disease (AD). Low density lipoprotein receptor-related protein 1 (LRP-1) is involved in the active outward transport of β-amyloid across the blood-brain barrier (BBB). The C667T polymorphism (rs1799986) of the LRP-1 gene has been inconsistently associated with AD in genetic studies. We aimed to elucidate the association of this polymorphism with in-vivo brain amyloid load of AD patients using amyloid PET with [(11)C]PiB. MATERIALS AND METHODS: 72 patients with very mild to moderate AD were examined with amyloid PET and C667T polymorphism was obtained using TaqMan PCR assays. The association of C667T polymorphism with global and regional amyloid load was calculated using linear regression and voxel based analysis, respectively. The effect of the previously identified modulator of amyloid uptake, the apolipoprotein E genotype, on this association was also determined. RESULTS: The regression analysis between amyloid load and C667T polymorphism was statistically significant (p = 0.046, β = 0.236). In an additional analysis ApoE genotype and gender were identified to explain further variability of amyloid load. Voxel based analysis revealed a significant (p < 0.05) association between C667T polymorphism and amyloid uptake in the temporo-parietal cortex bilaterally. ApoE did not interact significantly with the LRP-1 polymorphism. DISCUSSION: In conclusion, C667T polymorphism of LRP-1 is moderately but significantly associated with global and regional amyloid deposition in AD. The relationship appears to be independent of the ApoE genotype. This finding is compatible with the hypothesis that impaired amyloid clearance contributes to amyloid deposition in late-onset sporadic AD.

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YNIMG Journal 2008 Journal Article

Imaging of amyloid plaques and cerebral glucose metabolism in semantic dementia and Alzheimer’s disease

Alexander Drzezga
Timo Grimmer
Gjermund Henriksen
Isabelle Stangier
Robert Perneczky
Janine Diehl-Schmid
Chester A. Mathis
William E. Klunk

Semantic dementia (SD) is a rare clinical syndrome, assigned to the group of frontotemporal lobar degenerations (FTLD). Histopathological analysis has not revealed the deposition of amyloid plaques in the majority of SD cases, in contrast to dementia of the Alzheimer type (AD). However, based on clinical examination alone a reliable differentiation of the underlying pathology cannot be guaranteed, i. e. AD and SD may be confused in some cases. Our aim was to determine, whether AD and SD can be differentiated in vivo by means of amyloid plaque PET imaging. In groups of AD and SD patients, matched for gender, age and overall degree of cognitive impairment, cerebral glucose metabolism was examined with [18F]Fluorodeoxyglucose (FDG)-PET and cerebral amyloid plaque density was assessed using [11C]6-OH-BTA-1 (PIB)-PET. A volume-of-interest analysis (VOI), using the cerebellum as a reference region, and voxel-based statistical group comparisons (SPM2) were carried out between the patient groups and matched groups of healthy controls. To control for a potential influence of atrophy on the PET findings, a correction of partial volume effects was performed. Characteristic patterns of hypometabolism could be demonstrated in both clinically defined AD and SD with some regional overlap and subtle differences (AD: bilateral posterior cingulate, temporoparietal and frontal cortex; SD: left>right polar temporal, frontal mesial cortex). Compared with healthy controls, significant [11C]PIB amyloid plaque tracer binding was observed only in patients with AD (in bilateral temporoparietal, frontal and posterior cingulate cortex and the precuneus) but not in SD. This difference in amyloid plaque deposition could be reproduced in direct statistical comparison of AD and SD and clearly extended the metabolic differences between the patient groups. These findings support the notion that SD can be diagnosed in vivo as a separate entity from AD using amyloid plaque imaging. In general, amyloid plaque PET may complement neuropsychological assessment regarding reliable differential diagnosis of AD and FTLD dementias based on characterization of underlying pathology and may improve the definition of individual prognosis and the selection of patients for scientific trials.

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YNIMG Journal 2008 Journal Article

Multivariate and univariate neuroimaging biomarkers of Alzheimer's disease

Christian Habeck
Norman L. Foster
Robert Perneczky
Alexander Kurz
Panagiotis Alexopoulos
Robert A. Koeppe
Alexander Drzezga
Yaakov Stern

We performed univariate and multivariate discriminant analysis of FDG–PET scans to evaluate their ability to identify Alzheimer's disease (AD). FDG–PET scans came from two sources: 17 AD patients and 33 healthy elderly controls were scanned at the University of Michigan; 102 early AD patients and 20 healthy elderly controls were scanned at the Technical University of Munich, Germany. We selected a derivation sample of 20 AD patients and 20 healthy controls matched on age with the remainder divided into 5 replication samples. The sensitivity and specificity of diagnostic AD-markers and threshold criteria from the derivation sample were determined in the replication samples. Although both univariate and multivariate analyses produced markers with high classification accuracy in the derivation sample, the multivariate marker's diagnostic performance in the replication samples was superior. Further, supplementary analysis showed its performance to be unaffected by the loss of key regions. Multivariate measures of AD utilize the covariance structure of imaging data and provide complementary, clinically relevant information that may be superior to univariate measures.

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YNIMG Journal 2007 Journal Article

Multivariate network analysis of fiber tract integrity in Alzheimer’s disease

Stefan J. Teipel
Robert Stahl
Olaf Dietrich
Stefan O. Schoenberg
Robert Perneczky
Arun L.W. Bokde
Maximilian F. Reiser
Hans-Jürgen Möller

Axonal and dendritic integrity is affected early in Alzheimer’s disease (AD). Studies using region of interest or voxel-based analysis of diffusion tensor imaging data found significant decline of fractional anisotropy, a marker of fiber tract integrity, in selected white matter areas. We applied a multivariate network analysis based on principal component analysis to fractional anisotropy maps derived from diffusion-weighted scans from 15 AD patients, and 14 elderly healthy controls. Fractional anisotropy maps were obtained from an EPI diffusion sequence using parallel imaging to reduce distortion artifacts. We used high-dimensional image warping to control for partial volume effects due to white matter atrophy in AD. We found a significant regional pattern of fiber changes (p <0. 01) indicating that the integrity of intracortical projecting fiber tracts (including corpus callosum, cingulum and fornix, and frontal, temporal and occipital lobe white matter areas) was reduced, whereas extracortical projecting fiber tracts, including the pyramidal and extrapyramidal systems and somatosensory projections, were relatively preserved in AD. Effects of a univariate analysis were almost entirely contained within the multivariate effect. Our findings illustrate the use of a multivariate approach to fractional anisotropy data that takes advantage of the highly organized structure of anisotropy maps, and is independent of multiple comparison correction and partial volume effects. In agreement with post-mortem evidence, our study demonstrates dissociation between intracortical and extracortical projecting fiber systems in AD in the living human brain.

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