Friedreich Ataxia: Executive Control Is Related to Disease Onset and GAA Repeat Length
Tóm tắt
Friedreich ataxia (FRDA) is the most frequent inherited ataxia. Neuropsychological studies suggest that FRDA may be associated with specific cognitive impairment. Very little is known about the relation between cognitive performance, demographics and disease-related parameters, such as GAA repeat size, age of onset and disease duration. The present investigation aimed at assessing cognitive functions in a representative sample of FRDA patients and at identifying the most relevant disease-related parameters. Twenty-nine adult FRDA patients underwent neuropsychological tests assessing executive functions, attention, memory and visual perception. Performance was compared with 28 age- and education-matched controls as well as with standardized norms. The relation between neuropsychological outcome, demographical variables and disease-related parameters was assessed. Cognitive impairment affected only a subgroup of patients and mostly concerned attentional and executive functions. Good cognitive performance was associated with a later disease onset, shorter GAA repeat length and lower burden of disease. Age at disease onset has been found to be a good predictor when a cut-off of 14 years was chosen. No correlation was found between cognitive performance and education, age or disease duration. The present study extends earlier findings in FRDA showing that performance in attentional and executive function tasks is best predicted by the age at disease onset. Moreover, executive functions show a clear relationship to disease severity and repeat size of the shorter GAA allele. These findings therefore have important implications for patient counselling regarding education and career choices.
Tài liệu tham khảo
Pandolfo M. Friedreich's ataxia: clinical aspects and pathogenesis. Semin Neurol. 1999;19:311–21.
Wollmann T, Barroso J, Monton F, Nieto A. Neuropsychological test performance of patients with Friedreich's ataxia. J Clin Exp Neuropsychol. 2002;24:677–86.
Botez MI, Leveille J, Lambert R, Botez T. Single photon emission computed tomography (SPECT) in cerebellar disease: cerebello-cerebral diaschisis. Eur Neurol. 1991;31:405–12.
Botez-Marquard T, Botez MI. Cognitive behavior in heredodegenerative ataxias. Eur Neurol. 1993;33:351–7.
Ciancarelli I, Cofini V, Carolei A. Evaluation of neuropsychological functions in patients with Friedreich ataxia before and after cognitive therapy. Funct Neurol. 2010;25:81–5.
Nieto A, Correia R, De NE, Monton F, Hess S, Barroso J. Cognition in Friedreich ataxia. Cerebellum. 2012;11:834–44.
Campuzano V, Montermini L, Molto MD, Pianese L, Cossee M, Cavalcanti F, et al. Friedreich's ataxia: autosomal recessive disease caused by an intronic GAA triplet repeat expansion. Science. 1996;271:1423–7.
Schöls L, Amoiridis G, Przuntek H, Frank G, Epplen JT, Epplen C. Friedreich's ataxia. Revision of the phenotype according to molecular genetics. Brain. 1997;120(Pt 12):2131–40.
Bidichandani SI, Ashizawa T, Patel PI. The GAA triplet-repeat expansion in Friedreich ataxia interferes with transcription and may be associated with an unusual DNA structure. Am J Hum Genet. 1998;62:111–21.
Patel PI, Isaya G. Friedreich ataxia: from GAA triplet-repeat expansion to frataxin deficiency. Am J Hum Genet. 2001;69:15–24.
Bradley JL, Blake JC, Chamberlain S, Thomas PK, Cooper JM, Schapira AH. Clinical, biochemical and molecular genetic correlations in Friedreich's ataxia. Hum Mol Genet. 2000;9:275–82.
Schmucker S, Puccio H. Understanding the molecular mechanisms of Friedreich's ataxia to develop therapeutic approaches. Hum Mol Genet. 2010;19:R103–10.
Koeppen AH. Friedreich's ataxia: pathology, pathogenesis, and molecular genetics. J Neurol Sci. 2011;303:1–12.
Koeppen AH, Morral JA, Davis AN, Qian J, Petrocine SV, Knutson MD, et al. The dorsal root ganglion in Friedreich's ataxia. Acta Neuropathol. 2009;118:763–76.
Corben LA, Georgiou-Karistianis N, Fahey MC, Storey E, Churchyard A, Horne M, et al. Towards an understanding of cognitive function in Friedreich ataxia. Brain Res Bull. 2006;70:197–202.
White M, Lalonde R, Botez-Marquard T. Neuropsychologic and neuropsychiatric characteristics of patients with Friedreich's ataxia. Acta Neurol Scand. 2000;102:222–6.
Corben LA, Akhlaghi H, Georgiou-Karistianis N, Bradshaw JL, Egan GF, Storey E, et al. Impaired inhibition of prepotent motor tendencies in Friedreich ataxia demonstrated by the Simon interference task. Brain Cogn. 2011;76:140–5.
Klopper F, Delatycki MB, Corben LA, Bradshaw JL, Rance G, Georgiou-Karistianis N. The test of everyday attention reveals significant sustained volitional attention and working memory deficits in Friedreich ataxia. J Int Neuropsychol Soc. 2011;17:196–200.
Corben LA, Georgiou-Karistianis N, Bradshaw JL, Hocking DR, Churchyard AJ, Delatycki MB. The Fitts task reveals impairments in planning and online control of movement in Friedreich ataxia: reduced cerebellar-cortico connectivity? Neuroscience. 2011;192:382–90.
De Nobrega E, Nieto A, Barroso J, Monton F. Differential impairment in semantic, phonemic, and action fluency performance in Friedreich's ataxia: possible evidence of prefrontal dysfunction. J Int Neuropsychol Soc. 2007;13:944–52.
Mantovan MC, Martinuzzi A, Squarzanti F, Bolla A, Silvestri I, Liessi G, et al. Exploring mental status in Friedreich's ataxia: a combined neuropsychological, behavioral and neuroimaging study. Eur J Neurol. 2006;13:827–35.
Corben LA, Delatycki MB, Bradshaw JL, Churchyard AJ, Georgiou-Karistianis N. Utilisation of advance motor information is impaired in Friedreich ataxia. Cerebellum. 2011;10:793–803.
Hart RP, Kwentus JA, Leshner RT, Frazier R. Information processing speed in Friedreich's ataxia. Ann Neurol. 1985;17:612–4.
Fehrenbach RA, Wallesch CW, Claus D. Neuropsychologic findings in Friedreich's ataxia. Arch Neurol. 1984;41:306–8.
Schmitz-Hübsch T, du Montcel ST, Baliko L, Berciano J, Boesch S, Depondt C, et al. Scale for the assessment and rating of ataxia: development of a new clinical scale. Neurology. 2006;66:1717–20.
Lynch DR, Farmer JM, Tsou AY, Perlman S, Subramony SH, Gomez CM, et al. Measuring Friedreich ataxia: complementary features of examination and performance measures. Neurology. 2006;66:1711–6.
Schmitz-Hübsch T, Giunti P, Stephenson DA, Globas C, Baliko L, Sacca F, et al. SCA Functional Index: a useful compound performance measure for spinocerebellar ataxia. Neurology. 2008;71:486–92.
Subramony SH, May W, Lynch D, Gomez C, Fischbeck K, Hallett M, et al. Measuring Friedreich ataxia: interrater reliability of a neurologic rating scale. Neurology. 2005;64:1261–2.
Trauzettel-Klosinski S, Dietz K. Standardized assessment of reading performance: the New International Reading Speed Texts IReST. Invest Ophthalmol Vis Sci. 2012;53:5452–61.
Lehrl S, Merz J, Burkard G, Fischer B. Mehrfachwahl-Wortschatz Intelligenz Test. Erlangen: Peri-Med Fachbuch; 1991.
Zimmermann P, Fimm B. Testbatterie zur Aufmerksamkeitsprüfung. Version 2.1. Psytest: Herzogenath; 2007.
Aschenbrenner S, Tucha O, Lange KW. Regensburger Wortflüssigkeits-Test. Göttingen: Hogrefe; 2001.
Kohler J&BU. Der Planungstest - Softwareprogramm zur Diagnostik von Planungsstörungen. In: EnJoiME Software (Beck & Kohler GbR), 78467 Konstanz: 2004.
Bäumler G. Farbe-Wort-Interferenztest (FWIT). Göttingen Toronto Zürich: Hogrefe; 1985.
Härting C, Markowitsch HJ, Neufeld H, et al. Wechsler Gedächtnis-Test - Revidierte Fassung. Bern: Verlag Hans Huber; 2000.
Warrington EK, James M. The visual object and space perception battery VOSP. Bury St. Edmunds: Thames Valley Test Company; 1991.
Helmstaedter C, Durwen HF. The verbal learning and retention test. A useful and differentiated tool in evaluating verbal memory performance. Schweiz Arch Neurol Psychiatr. 1990;141:21–30.
E KH, Chen SH, Ho MH, Desmond JE. A meta-analysis of cerebellar contributions to higher cognition from PET and fMRI studies. Hum Brain Mapp. 2012. doi:10.1002/hbm.22194.
Schmahmann JD, Caplan D. Cognition, emotion and the cerebellum. Brain. 2006;129:290–2.
Kuper M, Dimitrova A, Thurling M, Maderwald S, Roths J, Elles HG, et al. Evidence for a motor and a non-motor domain in the human dentate nucleus—an fMRI study. Neuroimage. 2011;54:2612–22.
Thurling M, Kuper M, Stefanescu R, Maderwald S, Gizewski ER, Ladd ME, et al. Activation of the dentate nucleus in a verb generation task: a 7T MRI study. Neuroimage. 2011;57:1184–91.
Dum RP, Strick PL. An unfolded map of the cerebellar dentate nucleus and its projections to the cerebral cortex. J Neurophysiol. 2003;89:634–9.
Granziera C, Schmahmann JD, Hadjikhani N, Meyer H, Meuli R, Wedeen V, et al. Diffusion spectrum imaging shows the structural basis of functional cerebellar circuits in the human cerebellum in vivo. PLoS One. 2009;4:e5101.
Akhlaghi H, Corben L, Georgiou-Karistianis N, Bradshaw J, Storey E, Delatycki MB, et al. Superior cerebellar peduncle atrophy in Friedreich's ataxia correlates with disease symptoms. Cerebellum. 2011;10:81–7.
Della NR, Ginestroni A, Diciotti S, Salvatore E, Soricelli A, Mascalchi M. Axial diffusivity is increased in the degenerating superior cerebellar peduncles of Friedreich's ataxia. Neuroradiology. 2011;53:367–72.