Mobility is a critical component of independence and the quality of life of older persons. A significant number of older persons with mobility impairment demonstrate ischemic lesions in brain white matter (WM). We hypothesize that: Ss with a high level of vascular disease risk factors, will have a larger initial volume and higher accrual rate of WMSA; impaired mobility is caused by site-specific WMSA damaging fronto-parietal periventricular WM and WMSA accrual rate is stable allowing prediction of Ss """"""""at risk"""""""" for large WMSA increases. The link between ischemic WM lesions, which appear on MRI as WM signal abnormality (WMSA), and vascular disease risk factors (VDRF), as a cause, requires better definition. We propose to link VDRF to mobility impairment associated with WMSA and then determine if the risk factors predict incident cases. This will allow us to assess the magnitude of the VDRF as a cause of mobility impairment in order to plan new treatment strategies. We will use quantitative MRI and quantitative measures of mobility to link WMSA to mobility disorders. In preliminary studies, we separated older persons into groups with normal and impaired mobility. Automated quantitative segmentation of their MR images showed an increased volume of WMSA correlates with poorer mobility but not with age suggesting that the accrual of WMSA is related to a disease process. Site-specific periventricular WMSA involving frontal and parieto-occipital regions were present in Ss with impaired mobility. Follow-up MRIs on 14 Ss, 20 months after the initial scan, showed WMSA accrual was related to WMSA volume at baseline suggesting a continuous process and that the volume of WMSA increased at a fivefold greater rate in mobility impaired compared to normal Ss. We have recently determined that the quantitative measures of mobility are reliable. To move beyond correlation, we are proposing a 5- year project with 2 components: a cross-sectional analysis of 99 Ss 70 years and older stratified by mobility followed by a 4-year longitudinal follow-up. The cross-sectional component will determine the relationship of vascular disease risk factors, WMSA volume, WMSA location, use diffusion tensor imaging to identify/quantify damage to WM pathways and quantitative measures of mobility. Using the same measures, the longitudinal component will: 1) establish the link between vascular disease risk factors and mobility impairment; 2) establish clinical predictive value of imaging; 3) evaluate the causal relationship of WMSA to mobility; 4) refine our understanding of the anatomic substrate of mobility impairment; and 5) define the progression of this disorder.

Agency
National Institute of Health (NIH)
Institute
National Institute on Aging (NIA)
Type
Research Project (R01)
Project #
5R01AG022092-05
Application #
7473821
Study Section
Brain Disorders and Clinical Neuroscience 5 (BDCN)
Program Officer
Chen, Wen G
Project Start
2004-09-30
Project End
2010-07-31
Budget Start
2008-08-01
Budget End
2010-07-31
Support Year
5
Fiscal Year
2008
Total Cost
$477,688
Indirect Cost
Name
University of Connecticut
Department
Neurology
Type
Schools of Medicine
DUNS #
022254226
City
Farmington
State
CT
Country
United States
Zip Code
06030
Gupta, Puneet; Hagberg, Robert; Kaloudis, Electra et al. (2017) Severe and resistant hypertension in an older woman with claudication. J Am Soc Hypertens 11:475-479
Gupta, Puneet; White, William B (2017) Cardiovascular safety of therapies for type 2 diabetes. Expert Opin Drug Saf 16:13-25
Bohannon, Richard W; Wolfson, Leslie I; White, William B (2017) Functional reach of older adults: normative reference values based on new and published data. Physiotherapy 103:387-391
Cuadra, René H; White, William B (2016) Severe and refractory hypertension in a young woman. J Am Soc Hypertens 10:506-9
Sundermann, Erin Elizabeth; Wang, Cuiling; Katz, Mindy et al. (2016) Cholesteryl ester transfer protein genotype modifies the effect of apolipoprotein ?4 on memory decline in older adults. Neurobiol Aging 41:200.e7-200.e12
Abraham, Hazel Mae A; Wolfson, Leslie; Moscufo, Nicola et al. (2016) Cardiovascular risk factors and small vessel disease of the brain: Blood pressure, white matter lesions, and functional decline in older persons. J Cereb Blood Flow Metab 36:132-42
Petry, Nancy M; Alessi, Sheila M; Byrne, Shannon et al. (2015) Reinforcing adherence to antihypertensive medications. J Clin Hypertens (Greenwich) 17:33-8
Abraham, Hazel Mae A; White, C Michael; White, William B (2015) The comparative efficacy and safety of the angiotensin receptor blockers in the management of hypertension and other cardiovascular diseases. Drug Saf 38:33-54
Lipton, Richard B; Buse, Dawn C; Hall, Charles B et al. (2014) Reduction in perceived stress as a migraine trigger: testing the ""let-down headache"" hypothesis. Neurology 82:1395-401
Papp, Kathryn V; Kaplan, Richard F; Springate, Beth et al. (2014) Processing speed in normal aging: effects of white matter hyperintensities and hippocampal volume loss. Neuropsychol Dev Cogn B Aging Neuropsychol Cogn 21:197-213

Showing the most recent 10 out of 44 publications