Medications affecting the central nervous system (e.g., sedatives) are known to increase the risk of falls in the elderly. Another class of medications that may impair postural stability and gait consists of drugs that inhibit acetylcholine, a neurotransmitter widely distributed in the brain. Many of the medications most commonly prescribed to the elderly have an anticholinergic effect, and older individuals often take multiple anticholinergics including over-the-counter drugs. Another condition linked to gait/balance decrements is cerebrovascular disease, evident on MRI scans as hyperintense areas in the cerebral white matter - white matter hyperintensities (WMH). There is evidence that anticholinergic medications and cerebrovascular disease may have a synergistic effect such that older persons with a greater volume of WMH are more sensitive to anticholinergic medications thus, perhaps making them particularly vulnerable to any gait/balance deficits associated with these medications. To test this possibility we will recruit 150 normal elderly individuals who will be given tests of balance, gait, psychomotor speed and attention. We will obtain a blood sample to determine each subjects'cumulative anticholinergic burden (serum anticholinergic activity), and a structural MRI to measure the volume of WMH present in the subject's total brain, as well as in those white matter tracts known to carry cholinergic fibers. This study will examine whether the balance and gait performance of older individuals varies as a function of their serum anticholinergic activity and whether this effect of anticholinergic load is greater in older persons with co-existent cerebrovascular disease (i.e., greater volumes of WMH). We will also examine whether the effects that anticholinergic medications and WMH have on postural control and gait are mediated, to some degree, through the decrements that WMH and anticholinergic drugs produce in cognitive functioning - specifically in psychomotor speed and in divided and selective attention.

Public Health Relevance

Anticholinergic medications (both prescribed and over the counter) are commonly taken by elderly persons and may be an unrecognized contributor to balance and gait problems in the elderly and especially in persons who have vascular disease in their brain. If the proposed studies show that anticholinergic medications are associated with balance and gait problems, then reducing usage of these medications could lessen the mobility limitations present in many older persons

National Institute of Health (NIH)
National Institute on Aging (NIA)
Research Project (R01)
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Aging Systems and Geriatrics Study Section (ASG)
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Chen, Wen G
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University of Pittsburgh
Schools of Medicine
United States
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Sukits, Alison L; Nebes, Robert D; Chambers, April J et al. (2014) Intra-individual variability in gait and in cognitive performance are not related in the elderly. Neuropsychol Dev Cogn B Aging Neuropsychol Cogn 21:283-95
Lowry, Kristin A; Brach, Jennifer S; Nebes, Robert D et al. (2012) Contributions of cognitive function to straight- and curved-path walking in older adults. Arch Phys Med Rehabil 93:802-7
Nebes, Robert D; Pollock, Bruce G; Perera, Subashan et al. (2012) The greater sensitivity of elderly APOE ýý4 carriers to anticholinergic medications is independent of cerebrovascular disease risk. Am J Geriatr Pharmacother 10:185-92