Einsatz der Positronen-Emissions-Tomographie mit [18F]FDG für die Diagnostik von neurodegenerativen Erkrankungen aus dem frontotemporalen Formenkreis

FDG-PET als Maß für neuronale Schädigung wird bei verschiedenen neurodegenerativen Erkrankungen aus dem frontotemporalen Formenkreis diagnostisch eingesetzt. In der weiterführenden Diagnostik kommen darüber hinaus spezifische Radiotracer zum Einsatz. Hierbei befindet sich die Tau-PET aktuell in klinischer Erprobung. In der dargestellten Arbeit konnte bei Patienten mit T+ APS bei zwei Dritteln der Patienten eine zufriedenstellende Diagnosesicherheit erzielt werden. Ein Drittel der Patienten würde demnach von einer weiteren Bewertung mit spezifischeren Radioliganden profitieren. Bei Patienten mit Verdacht auf PSP schnitt die FDG-PET besser ab als bei Patienten mit Verdacht auf CBD. Die verbesserte Diagnostik geht einher mit der Möglichkeit neuer spezifischer Therapieansätze, insbesondere was den Einschluss in prospektive Therapiestudien angeht. In einer zweiten Arbeit wurde untersucht, ob Bildung bei Patienten mit FTD eine höhere Widerstandsfähigkeit bei einer Funktionsbeeinträchtigung des Gehirns bietet. Hierzu wurden 66 FTLD-Patienten (Alter 67 ± 8 Jahre) und 24 kognitiv gesunde Kontrollprobanden bewertet. Durch eine voxelbasierte Analyse konnten die FTLDassoziierten Regionen mit Hypometabolismus in der FDG-PET im Vergleich zu gesunden Kontrollprobanden dargestellt werden und einzelne FDG-PET-Werte wurden aus signifikanten Hirnregionen extrahiert. Bei der Korrelation dieser Werte mit MMSEWerten ergab sich ein Cluster im linken temporalen Kortex, der mit dem FDG-PET Hypometabolismus übereinstimmte. Die Werte dieses Clusters wurden für die Residualisierungsanalyse der kognitiven Leistung genutzt. Residualisierte MMSE-Werte korrelieren mit einer höheren Anzahl an Bildungsjahren und gelten als ein Surrogat der kognitiven Reserve. Insgesamt sprechen die Ergebnisse somit für ein Vorliegen einer kognitiven Reserve auch bei Patienten mit FTD. Im klinischen Alltag müssen daher bei der Interpretation der FDG-PET-Befunde von FTLD-Patienten die Bildungsjahre mitberücksichtigt werden

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

Objectives: Many predictive or influencing factors have emerged in investigations of the cognitive reserve model of patients with Alzheimer's disease (AD). For example, neuronal injury, which correlates with cognitive decline in AD, can be assessed by [F-18]-fluorodeoxyglucose positron-emission-tomography (FDG-PET), structural magnetic resonance imaging (MRI) and total tau in cerebrospinal fluid (CSFt-tau), 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: 110 initially mild cognitive impaired and demented subjects (age 71 +/- 8 years) with a final diagnosis of AD dementia were assessed at baseline by clinical mini-mental-state-examination (MMSE), FDG-PET, MRI and CSFt-tau. 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: FDG-PET correlated highly with clinical MMSE (R = - 0.49, p < .01), whereas hippocampal atrophy to MRI (R = -0.15, p = .14) and CSFt-tau, (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

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

BACKGROUND AND OBJECTIVE Reserve is defined as the ability to maintain cognitive functions relatively well at a given level of pathology. Early life experiences such as education are associated with lower dementia risk in general. However, whether more years of education guards against the impact of brain alterations also in frontotemporal dementia (FTD) has not been shown in a large patient collective. Therefore, we assessed whether education is associated with relatively high cognitive performance despite the presence of [18F]-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

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

OBJECTIVES: Many predictive or influencing factors have emerged in investigations of the cognitive reserve model of patients with Alzheimer's disease (AD). For example, neuronal injury, which correlates with cognitive decline in AD, can be assessed by [18F]-fluorodeoxyglucose positron-emission-tomography (FDG-PET), structural magnetic resonance imaging (MRI) and total tau in cerebrospinal fluid (CSFt-tau), 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: 110 initially mild cognitive impaired and demented subjects (age 71 ± 8 years) with a final diagnosis of AD dementia were assessed at baseline by clinical mini-mental-state-examination (MMSE), FDG-PET, MRI and CSFt-tau. 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: FDG-PET correlated highly with clinical MMSE (R = -0.49, p < .01), whereas hippocampal atrophy to MRI (R = -0.15, p = .14) and CSFt-tau (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

Clinical Routine FDG-PET Imaging of Suspected Progressive Supranuclear Palsy and Corticobasal Degeneration: A Gatekeeper for Subsequent Tau-PET Imaging?

Background: F-18-fluordeoxyglucose positron emission tomography (FDG-PET) is widely used for discriminative diagnosis of tau-positive atypical parkinsonian syndromes (T+APS). This approach now stands to be augmented with more specific tau tracers. Therefore, we retrospectively analyzed a large clinical routine dataset of FDG-PET images for evaluation of the strengths and limitations of stand-alone FDG-PET. Methods: A total of 117 patients (age 68.4 ± 11.1 y) underwent an FDG-PET exam. Patients were followed clinically for a minimum of one year and their final clinical diagnosis was recorded. FDG-PET was rated visually (positive/negative) and categorized as high, moderate or low likelihood of T+APS and other neurodegenerative disorders. We then calculated positive and negative predictive values (PPV/NPV) of FDG-PET readings for the different subgroups relative to their final clinical diagnosis. Results: Suspected diagnoses were confirmed by clinical follow-up (≥1 y) for 62 out of 117 (53%) patients. PPV was excellent when FDG-PET indicated a high likelihood of T+APS in combination with low to moderate likelihood of another neurodegenerative disorder. PPV was distinctly lower when FDG-PET indicated only a moderate likelihood of T+APS or when there was deemed equal likelihood of other neurodegenerative disorder. NPV of FDG-PET with a low likelihood for T+APS was high. Conclusions: FDG-PET has high value in clinical routine evaluation of suspected T+APS, gaining satisfactory differential diagnosis in two thirds of the patients. One third of patients would potentially profit from further evaluation by more specific radioligands, with FDG-PET serving gatekeeper function for the more expensive methods

Table_1_Clinical Routine FDG-PET Imaging of Suspected Progressive Supranuclear Palsy and Corticobasal Degeneration: A Gatekeeper for Subsequent Tau-PET Imaging?.DOCX

<p>Background: F-18-fluordeoxyglucose positron emission tomography (FDG-PET) is widely used for discriminative diagnosis of tau-positive atypical parkinsonian syndromes (T+APS). This approach now stands to be augmented with more specific tau tracers. Therefore, we retrospectively analyzed a large clinical routine dataset of FDG-PET images for evaluation of the strengths and limitations of stand-alone FDG-PET.</p><p>Methods: A total of 117 patients (age 68.4 ± 11.1 y) underwent an FDG-PET exam. Patients were followed clinically for a minimum of one year and their final clinical diagnosis was recorded. FDG-PET was rated visually (positive/negative) and categorized as high, moderate or low likelihood of T+APS and other neurodegenerative disorders. We then calculated positive and negative predictive values (PPV/NPV) of FDG-PET readings for the different subgroups relative to their final clinical diagnosis.</p><p>Results: Suspected diagnoses were confirmed by clinical follow-up (≥1 y) for 62 out of 117 (53%) patients. PPV was excellent when FDG-PET indicated a high likelihood of T+APS in combination with low to moderate likelihood of another neurodegenerative disorder. PPV was distinctly lower when FDG-PET indicated only a moderate likelihood of T+APS or when there was deemed equal likelihood of other neurodegenerative disorder. NPV of FDG-PET with a low likelihood for T+APS was high.</p><p>Conclusions: FDG-PET has high value in clinical routine evaluation of suspected T+APS, gaining satisfactory differential diagnosis in two thirds of the patients. One third of patients would potentially profit from further evaluation by more specific radioligands, with FDG-PET serving gatekeeper function for the more expensive methods.</p