1. Imaging Methods: Gait, Cognition and Mood Richard Camicioli MD University of Alberta Edmonton, Alberta rcamicio@ualberta.ca

2. Objectives To present approaches to the imaging investigation of age-related gait, cognitive and mood changes, emphasizing gait. To focus on various MRI approaches to the study of age-related gait change. To introduce functional imaging approaches. To highlight gaps and suggest directions for future research.

3. Gait, Cognition, Mood Gait Mood Cognition

4. Study Design Single-case studies Case-series Correlative Case-control studies –Selective –Nested Longitudinal studies –Cohort studies Population-based Selected samples –Clinical trials

5. Imaging Modalities Magnetic resonance imaging (MRI) –White matter rating/quantitation –Volumetric measurement –Diffusion tensor imaging –Magnetization transfer imaging –Spectroscopy –Functional MRI PET SPECT

6. Case Studies and Case Series Clues and Correlates

7. Group Studies Correlative Studies and Case- Controlled Studies

8. White Matter Rating Scales Manolio Fazekas and Schmidt Scheltens Wahlund Kapeller P Stroke 2003

9. ARWMC Ratings White matter lesions –0: No lesions (including symmetrical well-defined caps and bands) –1: Focal lesions –2: Beginning confluence of lesions –3: Diffuse involvement of an entire region Basal ganglia lesions –0: No lesions –1: 1 focal lesion (<5mm) –2: >1 focal lesion –3: Confluent lesions Wahlund LO Stroke 2001

10. Quantitative White Matter Measurement More reliable than visual rating More amenable to longitudinal rating Less prone to floor or ceiling effects More readily allows for anatomic specification

11. Longitudinal White Matter Change Annual change in white matter signal (but not change in grey matter, white matter or CSF volume) associated with impaired gait and balance (Short Physical Performance Battery) –Wolfson L et al J Neurol Sci 2005 Only 14 total subjects Other studies have similar findings –Whitman G et al Neurology 2001 Longidudinal follow up of 70 older people

12. Age-Related White Matter High Signal and Depression Some studies (not all) have found that ARWMD is related to depressive symptoms –LADIS study suggested that deep (not periventricular) changes are associated with depressive symptoms –Meta-analysis suggests both are associated Correlation with outcomes in some studies –Poorer response to therapy and persistence Longitudinal changes have been inconsistently related to symptoms –Chen PS Int Psychogeriatr 2006; Verslius CE Int J Geriatr Psychiatry 2006

13. Volumetric Approach Volumetric measurement of hippocampus and amygdala have been used in studies of cognition and mood –ROI and automated methods Automated method allow for segmentation of grey and white matter Voxel-based morphometry allows for unbiased comparison of groups and correlation with measures

14. Diffusion Tensor Imaging Diffusion tensor imaging is based on the measurement of diffusivity of water molecules Allows for assessment of integrity of white matter pathways –Fractional anisotropy (FA) and apparent diffusion coefficient (ADC) usually change in opposite direction in relation to disruption –Complements other methods have also been used (ie. Magnetization transfer and MR spectroscopy) Pathways can also be mapped using diffusion tensor tractography These methods are being applied to cognition and mood but should be applicable to gait.

15. Functional Imaging Modalities: MRI, PET and SPECT Measure changes during task performance, compared to a baseline task Walking is challenging to measure –MRI and PET affected by movement artifact Studies have looked at lower extremity movements and walking imagery SPECT has been used to look directly at walking

16. Conclusions Various study designs have provided useful insights into the neural correlates of gait, cognitive and mood impairment –An attainable goal is to examine these together to determine their unique and overlapping basis MRI techniques under development will likely provide further insights Other imaging and measurement approaches will provide convergent evidence and unique insights –Multimodal imaging is an important target

17. Suggested Future Directions Further application of new imaging techniques (DTI, high resolution MRI, etc) will provide additional insights into the neural basis of gait, cognitive and mood changes with aging –Convergent approaches improve confidence and provide complementary information Large scale epidemiological studies should include imaging Studies should examine gait, cognition and mood together High-risk investment may allow the development to measure the neural correlates of walking in real-time