Cerebrovascular disease is among the most common neurological diseases of aging and is increasing in prevalence with changing demographic trends. The two most common consequences of cerebrovascular disease are cognitive and motor decline, which are major contributors to poor health outcomes and mortality. Identifying associated factors, particularly ones for which treatments are available, is a priority for researchers in aging. Recent data suggest that antiphospholipid antibodies (aPL) increase in aging, and are present in about 35% of persons over the age of 80 years. While aPL increase risk of stroke by about two-fold, their relation to decline in cognitive and motor function, perhaps through an association with both clinical and subclinical cerebrovascular disease, is unclear. The proposed epidemiologic study will take advantage of a cohort of 1,100 community-dwelling women and men who are followed longitudinally with a high follow-up rate, and who come to autopsy with a high autopsy rate (R01AG17917), to test the hypotheses that aPL are related to cognitive and motor decline. The study will also examine the relation of aPL to cerebrovascular disease, including subclinical cerebrovascular disease assessed by complementary ante-mortem neuroimaging and postmortem neuropathology, and the extent to which aPL are related to cognitive and motor impairment after controlling for this disease. This would suggest the existence of neurobiologic mechanisms other than cerebrovascular disease linking aPL and cognitive and motor dysfunction. Finally, because factors with effects other than vascular may influence relations, the study will examine the role of makers of inflammation and altered blood-brain barrier permeability. The proposed study, relating aPL and other markers to cognitive and motor decline, and cerebrovascular disease in older, community-dwelling persons, will provide new knowledge regarding the role of aPL in common neurological conditions of aging. Because aPL are common vascular factors for which treatments are available, this study will provide new data which has the potential to improve public health by shifting current clinical practice paradigms and reducing the burden of neurological disease in aging.

Public Health Relevance

Cerebrovascular disease is increasing in prevalence with the aging population, and cognitive and motor decline, its'two most common consequences, are both major contributors to poor health outcomes and mortality. Identification of associated factors is priority for researchers in aging. These study relating blood vascular factors to cognitive and motor decline, and cerebrovascular disease, will fill a gap in knowledge in the field and has potential to provide data which will improve public health. an important

National Institute of Health (NIH)
National Institute on Aging (NIA)
Research Project (R01)
Project #
Application #
Study Section
Neurological, Aging and Musculoskeletal Epidemiology (NAME)
Program Officer
Anderson, Dallas
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
Rush University Medical Center
Schools of Medicine
United States
Zip Code
Pruzin, Jeremy J; Schneider, Julie A; Capuano, Ana W et al. (2017) Diabetes, Hemoglobin A1C, and Regional Alzheimer Disease and Infarct Pathology. Alzheimer Dis Assoc Disord 31:41-47
Thaker, A A; Weinberg, B D; Dillon, W P et al. (2017) Entorhinal Cortex: Antemortem Cortical Thickness and Postmortem Neurofibrillary Tangles and Amyloid Pathology. AJNR Am J Neuroradiol 38:961-965
Arvanitakis, Zoe; Capuano, Ana W; Leurgans, Sue E et al. (2017) The Relationship of Cerebral Vessel Pathology to Brain Microinfarcts. Brain Pathol 27:77-85
Arvanitakis, Zoe; Fleischman, Debra A; Arfanakis, Konstantinos et al. (2016) Association of white matter hyperintensities and gray matter volume with cognition in older individuals without cognitive impairment. Brain Struct Funct 221:2135-46
Arvanitakis, Zoe; Capuano, Ana W; Leurgans, Sue E et al. (2016) Relation of cerebral vessel disease to Alzheimer's disease dementia and cognitive function in elderly people: a cross-sectional study. Lancet Neurol 15:934-943
Lim, Andrew S P; Fleischman, Debra A; Dawe, Robert J et al. (2016) Regional Neocortical Gray Matter Structure and Sleep Fragmentation in Older Adults. Sleep 39:227-35
Adams, Hieab H H (see original citation for additional authors) (2016) Novel genetic loci underlying human intracranial volume identified through genome-wide association. Nat Neurosci 19:1569-1582
Buchman, Aron S; Wilson, R S; Shulman, Joshua M et al. (2016) Parkinsonism in Older Adults and Its Association With Adverse Health Outcomes and Neuropathology. J Gerontol A Biol Sci Med Sci 71:549-56
Boyle, Patricia A; Yu, Lei; Fleischman, Debra A et al. (2016) White matter hyperintensities, incident mild cognitive impairment, and cognitive decline in old age. Ann Clin Transl Neurol 3:791-800
Fleischman, Debra A; Yang, Jingyun; Arfanakis, Konstantinos et al. (2015) Physical activity, motor function, and white matter hyperintensity burden in healthy older adults. Neurology 84:1294-300

Showing the most recent 10 out of 27 publications