Author name cluster

Marcus Unterrainer

Possible papers associated with this exact author name in Arrow. This page groups case-insensitive exact name matches and is not a full identity disambiguation profile.

3 papers

1 author row

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.

Details DOI

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.

Details DOI

YNIMG Journal 2018 Journal Article

Coupling between physiological TSPO expression in brain and myocardium allows stabilization of late-phase cerebral [18F]GE180 PET quantification

Maximilian Deussing
Tanja Blume
Lena Vomacka
Christoph Mahler
Carola Focke
Andrei Todica
Marcus Unterrainer
Nathalie L. Albert

Objectives PET imaging of the 18 kDa translocator protein (TSPO), a biomarker of microglial activity, receives growing interest in clinical and preclinical applications of neuroinflammatory and neurodegenerative brain diseases. In globally affected brains, intra-cerebral pseudo reference regions are not feasible. Consequently, many brain-independent approaches have been attempted, including SUV analysis and normalization to muscle- or heart uptake, aiming to stabilize quantitative analysis. In this study, we systematically compared different image normalization methods for static late phase TSPO-PET imaging of rodent brain. Methods We first obtained gamma counter measurements for gold standard quantitation of [18F]GE180 uptake in brain of C57Bl/6 mice (N = 10) after PET, aiming to identify factors contributing significantly to the quantitative results. Subsequently, data from a large cohort of C57Bl/6 mice (N = 79) were compiled to precisely determine the weighted influence and variance attributable these factors by regression analysis. Scan-rescan variability and agreement with histology were used to validate the tested normalization methods in an Alzheimer's disease (AD) mouse model with pathologically increased TSPO expression (PS2APP; N = 24). Longitudinal data from AD model mice (N = 10) scanned at four different ages were used to challenge and validate the different normalization methods in a practical application. Results Gamma counter results revealed that injected dose, body weight and PET-measured radioactivity concentration in the ventral myocardium all significantly accounted for [18F]GE180 activity in the brain. Skeletal muscle activity had high test-retest variance in this PET only application and was therefore pursued no further. Regression analysis of the large scale evaluation showed that scaling to injected dose or SUV analysis accounted for little variance in brain activity (R2 < 0. 5), but inclusion of myocardial activity together with injected dose and body weight in the regression model accounted for most of the variance in brain uptake (R2 = 0. 94). Scan-rescan stability, correlation with histology and applicability for longitudinal examination in the disease model were also significantly improved by inclusion of myocadial uptake in the quantitative model. Conclusion Cerebral and myocardial TSPO expression are highly coupled under physiological conditions. Myocardial uptake has great potential for stabilization of static late phase [18F]GE180 quantification in brain in the absence of a valid intra-cerebral pseudo-reference region.

Details DOI