Age-related differences of cerebellar cortex and nuclei: MRI findings in healthy controls and its application to spinocerebellar ataxia (SCA6) patients
Dominik Jäschke,
Katharina M. Steiner,
Dae-In Chang,
Jens Claaßen,
Ellen Uslar,
Andreas Thieme,
Marcus Gerwig,
Viktor Pfaffenrot,
Thomas Hulst,
Alexander Gussew,
Stefan Maderwald,
Sophia L. Göricke,
Martina Minnerop,
Mark E. Ladd,
Jürgen R. Reichenbach,
Dagmar Timmann,
Andreas Deistung
Affiliations
Dominik Jäschke
Department of Neurology and Center for Translational Neuro- and Behavioral Sciences (C-TNBS), Essen University Hospital, University of Duisburg-Essen, Essen 45147, Germany; Department of Radiology and Nuclear Medicine, University Hospital Basel, Basel 4031, Switzerland
Katharina M. Steiner
Department of Neurology and Center for Translational Neuro- and Behavioral Sciences (C-TNBS), Essen University Hospital, University of Duisburg-Essen, Essen 45147, Germany; LVR-Hospital Essen, Department of Psychiatry and Psychotherapy, Medical Faculty, University of Duisburg-Essen, Essen 45147, Germany
Dae-In Chang
Department of Neurology and Center for Translational Neuro- and Behavioral Sciences (C-TNBS), Essen University Hospital, University of Duisburg-Essen, Essen 45147, Germany; Clinic for Psychiatry, Psychotherapy and Preventive Medicine, LWL-University Hospital of the Ruhr-University Bochum, Bochum 44791, Germany
Jens Claaßen
Department of Neurology and Center for Translational Neuro- and Behavioral Sciences (C-TNBS), Essen University Hospital, University of Duisburg-Essen, Essen 45147, Germany; Fachklinik für Neurologie, MEDICLIN Klinik Reichshof, Reichshof-Eckenhagen 51580, Germany
Ellen Uslar
Department of Neurology and Center for Translational Neuro- and Behavioral Sciences (C-TNBS), Essen University Hospital, University of Duisburg-Essen, Essen 45147, Germany
Andreas Thieme
Department of Neurology and Center for Translational Neuro- and Behavioral Sciences (C-TNBS), Essen University Hospital, University of Duisburg-Essen, Essen 45147, Germany
Marcus Gerwig
Department of Neurology and Center for Translational Neuro- and Behavioral Sciences (C-TNBS), Essen University Hospital, University of Duisburg-Essen, Essen 45147, Germany
Viktor Pfaffenrot
Erwin L. Hahn Institute for Magnetic Resonance Imaging, University of Duisburg-Essen, Essen 45141, Germany
Thomas Hulst
Department of Neurology and Center for Translational Neuro- and Behavioral Sciences (C-TNBS), Essen University Hospital, University of Duisburg-Essen, Essen 45147, Germany; Erasmus University College, Rotterdam 3011 HP, the Netherlands
Alexander Gussew
University Clinic and Outpatient Clinic for Radiology, Department for Radiation Medicine, University Hospital Halle (Saale), Ernst-Grube-Str. 40, Halle (Saale) 06120, Germany
Stefan Maderwald
Erwin L. Hahn Institute for Magnetic Resonance Imaging, University of Duisburg-Essen, Essen 45141, Germany
Sophia L. Göricke
Institute of Diagnostic and Interventional Neuroradiology, Essen University Hospital, University of Duisburg-Essen, Essen 45141, Germany
Martina Minnerop
Institute of Neuroscience and Medicine (INM-1), Research Centre Juelich, Juelich 52425, Germany; Department of Neurology, Center for Movement Disorders and Neuromodulation, Medical Faculty and University Hospital Düsseldorf, Heinrich-Heine University Düsseldorf, Düsseldorf 40225, Germany; Institute of Clinical Neuroscience and Medical Psychology, Medical Faculty and University Hospital Düsseldorf, Heinrich-Heine University Düsseldorf, Düsseldorf 40225, Germany
Mark E. Ladd
Erwin L. Hahn Institute for Magnetic Resonance Imaging, University of Duisburg-Essen, Essen 45141, Germany; Medical Physics in Radiology, German Cancer Research Center (DKFZ), Heidelberg 69120, Germany; Faculty of Physics and Astronomy and Faculty of Medicine, Heidelberg University, Heidelberg 69120, Germany
Jürgen R. Reichenbach
Medical Physics Group, Institute of Diagnostic and Interventional Radiology, Jena University Hospital, Jena 07743, Germany
Dagmar Timmann
Department of Neurology and Center for Translational Neuro- and Behavioral Sciences (C-TNBS), Essen University Hospital, University of Duisburg-Essen, Essen 45147, Germany; Erwin L. Hahn Institute for Magnetic Resonance Imaging, University of Duisburg-Essen, Essen 45141, Germany
Andreas Deistung
Department of Neurology and Center for Translational Neuro- and Behavioral Sciences (C-TNBS), Essen University Hospital, University of Duisburg-Essen, Essen 45147, Germany; University Clinic and Outpatient Clinic for Radiology, Department for Radiation Medicine, University Hospital Halle (Saale), Ernst-Grube-Str. 40, Halle (Saale) 06120, Germany; Medical Physics Group, Institute of Diagnostic and Interventional Radiology, Jena University Hospital, Jena 07743, Germany; Corresponding author at: University Clinic and Outpatient Clinic for Radiology, Department for Radiation Medicine, University Hospital Halle (Saale), Ernst-Grube-Str. 40, Halle (Saale) 06120, Germany.
Understanding cerebellar alterations due to healthy aging provides a reference point against which pathological findings in late-onset disease, for example spinocerebellar ataxia type 6 (SCA6), can be contrasted. In the present study, we investigated the impact of aging on the cerebellar nuclei and cerebellar cortex in 109 healthy controls (age range: 16 – 78 years) using 3 Tesla magnetic resonance imaging (MRI). Findings were compared with 25 SCA6 patients (age range: 38 – 78 years). A subset of 16 SCA6 (included: 14) patients and 50 controls (included: 45) received an additional MRI scan at 7 Tesla and were re-scanned after one year. MRI included T1-weighted, T2-weighted FLAIR, and multi-echo T2*-weighted imaging. The T2*-weighted phase images were converted to quantitative susceptibility maps (QSM). Since the cerebellar nuclei are characterized by elevated iron content with respect to their surroundings, two independent raters manually outlined them on the susceptibility maps. T1-weighted images acquired at 3T were utilized to automatically identify the cerebellar gray matter (GM) volume. Linear correlations revealed significant atrophy of the cerebellum due to tissue loss of cerebellar cortical GM in healthy controls with increasing age. Reduction of the cerebellar GM was substantially stronger in SCA6 patients. The volume of the dentate nuclei did not exhibit a significant relationship with age, at least in the age range between 18 and 78 years, whereas mean susceptibilities of the dentate nuclei increased with age. As previously shown, the dentate nuclei volumes were smaller and magnetic susceptibilities were lower in SCA6 patients compared to age- and sex-matched controls. The significant dentate volume loss in SCA6 patients could also be confirmed with 7T MRI. Linear mixed effects models and individual paired t-tests accounting for multiple comparisons revealed no statistical significant change in volume and susceptibility of the dentate nuclei after one year in neither patients nor controls. Importantly, dentate volumes were more sensitive to differentiate between SCA6 (Cohen's d = 3.02) and matched controls than the cerebellar cortex volume (d = 2.04). In addition to age-related decline of the cerebellar cortex and atrophy in SCA6 patients, age-related increase of susceptibility of the dentate nuclei was found in controls, whereas dentate volume and susceptibility was significantly decreased in SCA6 patients. Because no significant changes of any of these parameters was found at follow-up, these measures do not allow to monitor disease progression at short intervals.
