Age-related differences of cerebellar cortex and nuclei: MRI findings in healthy controls and its application to spinocerebellar ataxia (SCA6) patients

• Published in: NeuroImage (Orlando, Fla.) Vol. 270; p. 119950
• Main Authors: Jäschke, Dominik, Steiner, Katharina M., Chang, Dae-In, Claaßen, Jens, Uslar, Ellen, Thieme, Andreas, Gerwig, Marcus, Pfaffenrot, Viktor, Hulst, Thomas, Gussew, Alexander, Maderwald, Stefan, Göricke, Sophia L., Minnerop, Martina, Ladd, Mark E., Reichenbach, Jürgen R., Timmann, Dagmar, Deistung, Andreas
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 15.04.2023; Elsevier Limited; Elsevier
• Subjects: Adolescent; Adult; Age; Aged; Aging; Ataxia; Atrophy; Atrophy - pathology; Brain; Cerebellar Cortex - diagnostic imaging; Cerebellar Cortex - pathology; Cerebellar Nuclei - diagnostic imaging; Cerebellum; Cerebellum - pathology; Cortex; Dentate nucleus; Humans; Iron; Magnetic fields; Magnetic resonance imaging; Magnetic Resonance Imaging - methods; Middle Aged; MRI; Neuroimaging; Nuclei; Older people; Pathology; Quantitative susceptibility mapping; Spinocerebellar ataxia; Spinocerebellar ataxia type 6; Spinocerebellar Ataxias - diagnostic imaging; Spinocerebellar Ataxias - pathology; Statistical analysis; Substantia grisea; Susceptibility; Young Adult; Cerebellum; SCA6; MRI; Quantitative susceptibility mapping; R; MP-RAGE; BW; WM; Ataxia; FLAIR; Dentate nucleus; DNbulk; VBM; ppb; SWI; GM; HEIDI; QSM; Spinocerebellar ataxia type 6; TA; DCN; DNsil; TE; TI; SHARP; GRE; FA; T1w; TR
• ISSN: 1053-8119; 1095-9572
• DOI: 10.1016/j.neuroimage.2023.119950

•Cerebellar nuclei are discernible on susceptibility maps (QSM) acquired at 3 Tesla in healthy subjects and patients with SCA6.•The QSM-based volume of the dentate nuclei in adults is independent of age.•Dentate nuclei are significantly atrophied in SCA6.•The amount of iron of the dentate nuclei is reduced in SCA6.•Volume and iron concentration of the dentate nuclei did not show reliable changes in SCA6 patients within one year. 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. [Display omitted]