TY  - JOUR
AU  - Maas, Roderick P P W M
AU  - Garcia-Moreno, Hector
AU  - Faber, Jennifer
AU  - Gonzalez, Carlos
AU  - Schöls, Ludger
AU  - de Vries, Jeroen J
AU  - Bushara, Khalaf
AU  - Reetz, Kathrin
AU  - Onyike, Chiadi U
AU  - Jacobi, Heike
AU  - Erdlenbruch, Friedrich
AU  - Infante, Jon
AU  - Santana, Magda M
AU  - Hübener-Schmid, Jeannette
AU  - de Almeida, Luís Pereira
AU  - Lima, Manuela
AU  - Giunti, Paola
AU  - Klockgether, Thomas
AU  - van de Warrenburg, Bart P C
TI  - Cognitive impairment in SCA3: A multi-center cohort study with demographic, imaging, and biomarker correlates.
JO  - Neurobiology of disease
VL  - 220
SN  - 0969-9961
CY  - [Amsterdam]
PB  - Elsevier
M1  - DZNE-2026-00212
SP  - 107301
PY  - 2026
AB  - Cognitive deficits are common in spinocerebellar ataxia type 3 (SCA3), but their neurobiological correlates remain largely unknown.To investigate cognitive performance in a large international cohort of SCA3 mutation carriers covering the entire disease course and to explore associations with posterior cerebellar volumes, basal ganglia and thalamus volumes, and plasma neurofilament light chain (NfL) concentration.The Montreal Cognitive Assessment (MoCA) was used to evaluate cognitive impairment in this prospective, observational cohort study involving 13 ataxia referral centers. Standardized motor assessments, brain MR imaging, and peripheral blood biosampling were also performed.MoCA data were collected from 61 pre-ataxic SCA3 mutation carriers, 231 ataxic SCA3 patients, and 111 healthy controls. After adjustments for educational level and age, there were significant differences in MoCA total score, as well as visuospatial/executive, attention, language, and abstraction subscores, between healthy controls and ataxic, but not pre-ataxic individuals. MoCA scores declined with ataxia severity, especially in patients with a lower educational level. Patients with a MoCA score < 26 had lower pallidal volumes and higher plasma NfL concentrations than those with a score ≥ 26. However, only the interaction term between ataxia severity and educational level was independently associated with cognitive performance in multivariable regression analyses containing demographic, clinical, volumetric, and biochemical parameters.Cognitive deficits in SCA3 generally appear after clinical ataxia onset and progress in parallel with ataxia severity, especially in patients with a lower cognitive reserve. Other measured biochemical and imaging parameters did not have a significant additional contribution.
KW  - Humans
KW  - Male
KW  - Female
KW  - Middle Aged
KW  - Cognitive Dysfunction: diagnostic imaging
KW  - Cognitive Dysfunction: etiology
KW  - Cognitive Dysfunction: blood
KW  - Cognitive Dysfunction: psychology
KW  - Adult
KW  - Biomarkers: blood
KW  - Magnetic Resonance Imaging
KW  - Machado-Joseph Disease: complications
KW  - Machado-Joseph Disease: diagnostic imaging
KW  - Machado-Joseph Disease: psychology
KW  - Machado-Joseph Disease: genetics
KW  - Machado-Joseph Disease: blood
KW  - Cohort Studies
KW  - Neurofilament Proteins: blood
KW  - Aged
KW  - Prospective Studies
KW  - Mental Status and Dementia Tests
KW  - Cerebellum (Other)
KW  - Cognition (Other)
KW  - Machado-Joseph disease (Other)
KW  - Spinocerebellar ataxia type 3 (Other)
KW  - Biomarkers (NLM Chemicals)
KW  - Neurofilament Proteins (NLM Chemicals)
KW  - neurofilament protein L (NLM Chemicals)
LB  - PUB:(DE-HGF)16
C6  - pmid:41654200
DO  - DOI:10.1016/j.nbd.2026.107301
UR  - https://pub.dzne.de/record/285346
ER  -