1. Spinocerebellar Ataxia Type 8 (SCA-8) The Cognitive and Psychiatric Profile Lorna Torrens, Elaine Burns, Jon Stone, Mary Porteous, Adam Zeman, Helen Wright Robert Fergusson Unit, Royal Edinburgh Hospital; Western General Hospital, Edinburgh

2. Case History - Referral, 1998 46 year old man with 5 year history: neurological signs –slurred speech, ataxia, impaired dexterity cognitive decline –forgetfulness, difficulty with divided attention personality change –labile mood, aggressive outbursts, inflexibility

3. Case History - Examination Mild limb ataxia Dysarthric, slowed repetitive tongue movements MMSE 30/30 Buoyant mood, poor insight

4. Cognitive Screening Predicted FSIQ 110 but < 20th centile on: –Stroop –Trails A and B –Verbal/Category fluency –Immediate/delayed recall of story –Rey Osterreith figure Wisconsin (very poor)

5. MRI Scan

6. Family History Mother, 75 years old –impulsive and inflexible from 40s –dysarthric –incongruous affect –category fluency: 6 (animals), 4 (letter) –failed Luria test (5 trials)

7. Spinocerebellar Ataxia Type 8 (SCA 8) Koob et al, Nature Genetics, 1999;21:379-384 Family: 21 affected, 20 unaffected carriers: riskSCA-8 is a risk factor for expression of condition DNA based triplet repeat disorder (as is Huntingtons Disease) One of an enlarging family of SCAs Unusual - the repeat expansion is transcribed but not translated Myotonic Dystrophy - same mechanism

8. Reported Clinical Features of SCA-8 Cerebellar Signs (almost all) Upper Motor Neuron Signs (approx 50%) Cognitive Impairments: –26% of 68 patients covered in 11 studies (crude measures?)

9. SCA-8: Demographics, MRI

10. SCA 8: Neuropsychiatric symptoms

11. Schmahmann & Sherman 1998 Cerebellar Cognitive Affective Syndrome 20 Cases of Diseases confined to the cerebellum resulting in impaired executive function, visuo-spatial skills and memory. Personality change including disinhibition and blunting of affect

12. The SCA-8 expansion is associated with neurological and upper motor neuron signs. The SCA-8 expansion is associated with neurological and upper motor neuron signs. Are there also cognitive (specifically executive) and / or affective links? Are there also cognitive (specifically executive) and / or affective links?

13. The Tests Methodology Pre-Morbid IQ Current FSIQ Memory Screening Executive Tests

14. Executive Function Tests COWAT – Verbal Initiation, Speed Stroop – Speed, sustained attention, attentional switching Hayling and Brixton – Verbal initiation, suppression, speed, rule detection and following TEA – Visual Elevator Subtest – attentional switching, speed (MWCST) (BADS 6 Elements)

15. The Results...

16. SCA- 8: Mean Scores Controls: Mean Scores FSIQMemory Executive Tests

17. Average WAIS III Index Scores SCA-8 Subjects

18. SCA- 8 (Atrophy): CB (Scores percentiles) Control 1 (Scores percentiles) FSIQMemory Executive Tests

19. RESULTS Significant difference in performance executive function tests (p = 0.007) Non significant trend towards difference in performance on Visual Memory Main discrepancies stemming from Hayling (p = 0.005) and Stroop (0.015) Least difference in performance on Brixton

20. PFSIQ: SCA-8 vs Controls

21. Mean Executive Function Tests: SCA-8 vs Controls

22. Stroop:SCA-8 vs Controls COWAT: SCA-8 vs Controls

23. TEA: SCA-8 vs Controls Brixton: SCA-8 vs Controls Hayling: SCA-8 vs Controls

24. ASPECTS OF EXECUTIVE FUNCTION? Verbal Initiation/Speed - COWAT (p = 0.10), Brixton (but controls) Inhibition of automatic responses - Accuracy vs Speed (Hayling, Stroop 71 vs 56 secs for part I) Processing load ?

26. Is there an affective component?

27. BDI-II Minimal Mild HADS - Depression Normal

28. HADS - Anxiety BAI Minimal Mild Moderate Normal

29. Anxiety Symptoms Reported Wobbliness in legs Unsteady Numbness or Trembling Hands Shaking Shaky

30. Conclusions SCA-8 linked to cognitive change: –Executive Problems – PS (not necessarily linked to motor problems) SCA-8 may have an affective component: –Mild depression (Insufficient to account for cognitive deficits) –Anxiety (may reflect cerebellar symptoms as opposed to affective disorder)

31. Future Thoughts Progression –re-test in approx 2 years Mechanisms –results from present study do not elucidate the role of the cerebellum in cognition as SCA-8 may affect other brain regions (work underway)