Objective: Evaluate prospectively cognitive dysfunction in subjects with SCA2 using Mini Mental Examination (MMSE) and Montreal Cognition Assesment (MOCA), looking for correlation between cognitiion and motor disability, clinical variables and potentially modifier genes.

Background: Cognitive deficits in patients with cerebellar degeneration, including SCA2 have been shown. Studies on SCA2 did not find a clear change in cognitive scores in longitudinal observations. Although we have previously showed a potential association between mitochondrial polymorphism A1098G and cognitive dysfunction, little is known about factors that interfere with cognitive impairment in patients with SCA2.

Method: Symptomatic subjects with SCA2 were submitted to MMSE and MOCA; Beck Depression Inventory; motor scales: Scale for Assessment and Rating of Ataxia (SARA), and Neurologic Examination Score for Spinocerebellar Ataxia (NESSCA), SCA Functional-Index (SCAFI), and Composite-Cerebellar-Functional-Score (CCFS) at baseline and 12 months of follow up. Clinical variables, CAG repeat length at ATXN2 as well as at  ATXN1, ATXN3, ATXN7, CACNA1A and RAI1 were explored as modifiers factors.

Results: 49 SCA2 patients were studied . 78% of patients are in the normal range of MMSE, but 75% presented reduced  MOCA scores. At baseline, all motor scales showed correlation with MMSE and MOCA ( p<0.01), while only MOCA correlated with disease duration and CAG expanded repeat at ATXN2( p 0.05). After one year, SARA and NESSCA progressed on average 1.75(CI 95% 0.92-2.57) 1.45 (CI 95% 0.74-2.16) , respectively. In contrast,  MMSE and MOCA scores were apparently stable - deltas being -0.45 ( -1.71 - 0.29) and -0.42 (-1.56-0.73) points (p=0.22 and 0.45), respectively. Delta MMSE were inversely correlated with the CAGexp at ATXN2 (rho=-0.36, p< 0.05). The other risk factors (age, CAG repeat numbers at genes of interest) did not correlate with deltas of MOCA and of MMSE.

Conclusion: Executive, memory, language and visuospatial dysfunctions, detected by MOCA, are quite common in SCA2. Disease duration correlated with MOCA, and motor scores  correlated with MMSE and MOCA. Cognitive scores did not change after one year. Results support the suggestion that speed of progression of motor and cognitive dysfunctions are dissociated. On exploratory analysis, carriers of larger expansions presented worse deltas on MMSE. Future clinical trials should consider these differences in their outcomes .

References: Burk K, Globas C, Bosch S et al. Cognitive deficits in spinocerebellar ataxia 2. Brain 1999, 122: 769-777. Cancel G, Dürr A, Didierjean O et al .Molecular and clinical correlations in spinocerebellar ataxia 2: a study of 32 families. Hum Mol Genet. 1997 May;6(5):709-15 De Castilhos RM, Furtado GV, Gheno TC et al. Spinocerebellar ataxias in Brazil–frequencies and modulating effects of related genes. Cerebellum. 2014 Feb;13(1):17-28. Fancellu R, Pariidi D, Tomasello C et al. Longitudinal study of cognitive and psychiatric functions in spinocerebellar ataxia types 1 and 2. J Neurol 2013, 260:3134-3143. Kawai Y, Suenaga M, Watanabe H, Sobue G. Cognitive impairment in Spinocerebellar degeneration. Eur Neurol 2009; 61: 257-268. Le Pira F, Giuffrida S, Maci T et al . Dissociation between motor and cognitive impairment in SCA2: evidence from a follow up study. J Neurol, 2007; 254: 1455-1456. Le Pira F, Zappala G, Saponara R et al. Cognitive findings in spinocerebellar ataxia type 2: relationship to genetic and clinical variables. J Neurol Sci 2002;202:53-57. Magaña JJ, Velázquez-Pérez L, Cisneros B .Spinocerebellar ataxia type 2: clinical presentation, molecular mechanisms, and therapeutic perspectives.Mol Neurobiol. 2013 Feb;47(1):90-104. Monte T, , Reckziegel ER, Augustin MC et al.The progression rate of spinocerebellar ataxia type 2 changes with stage of disease. Orphanet J Rare Dis. 2018 Jan 25;13(1):20. Moriarty A, Cook A, Hunt H, Adams ME, Cipolotti L, Giunti P. A longitudinal investigation into cognition and disease progression in spinocerebellar ataxia types 1,2,3,6 and 7. Orphanet Journal of Rare Diseases, 2016:11-18.

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