Abstract Details

Title White Matter Hyperintensities in Recently Menopausal Women Are Associated with Platelet-Derived Surrogate Markers of Cardiovascular Risk

Topic Neurotoxicology

Presentation(s) IN8 - (-)

Poster/Presentation
Number 002

Objective

Background In older persons, WMH increase with age and are associated with an increased risk of mild cognitive impairment and stroke. Yet these relationships in younger, healthy persons are not known.

Design/Methods Recently menopausal women (n=95) with median (range) age of 53 (45-58) enrolled in the Kronos Early Estrogen Prevention Study (KEEPS) at Mayo Clinic participated in an imaging sub-study. A semi-automated algorithm was used to quantify WMH prior to (baseline) and 18, 36 and 48 months after randomization to hormone treatment. Baseline WMH load and changes in WMH volume at 48 months were correlated with conventional and non-conventional CV risk factors at baseline and the change in cognitive function at 48 months. Adjustments for age, time past menopause, ApoE ?4 were performed using multivariate linear regression models in the entire group of subjects.

Results At baseline, no correlations were found between WMH and conventional CV risk factors. However, platelet activation as measured by expression of fibrinogen receptors (glycoprotein Iib/IIIa complex measured by PAC1 binding) associated with baseline WMH volume (p=0.04). At 48 months, WMH volume increased from baseline (median (IQR)=359.6 (205, 568)mm3). Increases in WMH correlated with the number of baseline platelet-derived and thrombogenic MV (p=0.03). Changes in WMH volume did not correlate with changes in cognitive function over 48 months.

Conclusions Activated platelets and thrombogenic MV as surrogate markers of cardiovascular risk contribute to progression of WMH. Increases in WMH do not appear to impact cognitive performance in this healthy cohort of recently menopausal women.

Authors/Disclosures
PRESENTER	No disclosure on file
	No disclosure on file
Nirubol Tosakulwong	Nirubol Tosakulwong has nothing to disclose.
Timothy Lesnick	No disclosure on file
	No disclosure on file
	No disclosure on file
	No disclosure on file
	No disclosure on file
Peter Fuhr, MD, FAAN	The institution of Dr. Fuhr has received research support from Roche.
	No disclosure on file
Matthew Senjem (Mayo Clinic)	Matthew Senjem has received stock or an ownership interest from Align Technology, Inc.. Matthew Senjem has received stock or an ownership interest from Inovio Biomedical Corp.. Matthew Senjem has received stock or an ownership interest from Johnson & Johnson. Matthew Senjem has received stock or an ownership interest from Mesa Laboratories, Inc.. Matthew Senjem has received stock or an ownership interest from Nvidia Inc.. Matthew Senjem has received stock or an ownership interest from LHC Group, Inc.. Matthew Senjem has received stock or an ownership interest from Natus Medical Incorporated. Matthew Senjem has received stock or an ownership interest from Varex Imaging Corporation. Matthew Senjem has received personal compensation in the range of $100,000-$499,999 for serving as a IT Technical Specialist II with Mayo Clinic.
Prashanthi Vemuri, PhD (Mayo Clinic)	The institution of Dr. Vemuri has received research support from NIH.
Clifford R. Jack, Jr., MD (Mayo Clinic)	The institution of Dr. Jack has received research support from NIH. The institution of Dr. Jack has received research support from Alexander Family Alzheimer's Disease Research Professorship of the Mayo Clinic.
	No disclosure on file
	No disclosure on file
	No disclosure on file
Kejal Kantarci, MD (Mayo Clinic)	The institution of Dr. Kantarci has received research support from Eli Lilly. The institution of Dr. Kantarci has received research support from NIH. The institution of Dr. Kantarci has received research support from ADDF.

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