Abstract Details

Title Neural Correlates Associated with Executive Function in Patients with ATP1A3 Mutations

Topic Movement Disorders

Presentation(s) S41 - Imaging in Movement Disorders (4:47 PM-4:58 PM)

Poster/Presentation
Number 008

Background ATP1A3 gene mutations have been shown to cause rapid-onset dystonia-parkinsonism (RDP) and alternating hemiplegia of childhood (AHC). In addition to motor symptoms, RDP and AHC have been shown to alter several cognitive domains, including executive function.

Objective

The purpose of this study is to evaluate the relationship between brain structure and executive function in patients with ATP1A3 gene mutations of AHC and RDP. We hypothesized that ATP1A3 gene mutations of RDP and AHC affect gray matter volume in areas of the cerebello-thalamo-cortical pathway, which is believed to be involved in executive function and plays a role in other movement disorders.

Design/Methods T1-weighted images were obtained using a Skyra 3.0-T MRI scanner (Siemens Healthcare, Erlangen, Germany) from 17 patients with either RDP or AHC. These images were processed using standard methods, and volumetric tissue region of interest maps were made using Dartel high-dimensional warping and SPM8 new segment procedure, as implemented in the VBM8 toolbox. Wisconsin Card Sort Task (WCST) total and perseverative errors were obtained as measures of executive function.

Results

Pearson partial correlation adjusted for age and sex demonstrated statistically significant (p≤0.05) correlations between WCST errors and gray matter volume in the thalamic and prefrontal regions (range: R = -0.58 to -0.63), with increasing errors associated with decreasing volume. No significant correlations were identified in cerebellum.

Conclusions

These results suggest that AHC- and RDP-related decreases in executive function may be associated with changes in gray matter volume in prefrontal and thalamic regions. These same regions are known to be associated with executive dysfunction in other neurodegenerative diseases. Replication using a larger sample size, and exploration of the underlying mechanism could help further our understanding of the ATP1A3 mutation phenotype and lead us toward potential treatments.

Authors/Disclosures
Caroline Wilson, MD (Caroline Wilson) PRESENTER	Ms. Wilson has nothing to disclose.
Jared Cook	No disclosure on file
Beverly Snively	The institution of Beverly Snively has received research support from National Institutes of Health. The institution of Beverly Snively has received research support from Duke Endowment. The institution of Beverly Snively has received research support from Department of Defense. The institution of Beverly Snively has received research support from PCORI.
	No disclosure on file
	No disclosure on file
Kathleen J. Sweadner, PhD (Massachusetts General Hospital and Harvard Medical School)	The institution of Dr. Sweadner has received research support from Hope for Annabel, AHC Foundation, and CureAHC. The institution of Dr. Sweadner has received research support from the Chan-Zuckerberg Initiative.
Ihtsham Haq, MD, FAAN (University of Miami Miller School of Medicine)	The institution of Dr. Haq has received research support from NINDS. The institution of Dr. Haq has received research support from the Parkinson's Foundation. The institution of Dr. Haq has received research support from NIMH.
Laurie J. Ozelius, PhD	The institution of Dr. Ozelius has received research support from NIH. Dr. Ozelius has received intellectual property interests from a discovery or technology relating to health care.
Allison Brashear, MD, MBA, FAAN (Univeristy of Buffalo)	Dr. Brashear has received personal compensation for serving as an employee of McKnight Brain Res Found. Dr. Brashear has received personal compensation for serving as an employee of American Board of Psychiatry and Neurology. Dr. Brashear has received personal compensation in the range of $10,000-$49,999 for serving as an officer or member of the Board of Directors for ABPN. Dr. Brashear has received personal compensation in the range of $10,000-$49,999 for serving as an officer or member of the Board of Directors for McKnight Brain Research Foundation i. Dr. Brashear has received personal compensation in the range of $0-$499 for serving as an officer or member of the Board of Directors for Care Directions- start up . Dr. Brashear has stock in Caredirections . The institution of Dr. Brashear has received research support from NINDS. Dr. Brashear has received publishing royalties from a publication relating to health care. Dr. Brashear has received personal compensation in the range of $500-$4,999 for serving as a Special government employee and study section reviewer with NIH. Dr. Brashear has received personal compensation in the range of $0-$499 for serving as a Adminstrative board -travel reimbursement with AAMC.
Christopher T. Whitlow, MD (Wake Forest School of Medicine)	Dr. Whitlow has nothing to disclose.

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