Research studies on the cognitive effects of normal aging typically recruit older subjects who are well educated and who claim to be in good health. The rationale is that any cognitive impairments seen in such persons will reflect the effects of normal aging rather than poor education or disease. However, even such highly selected older persons often suffer from a variety of medical conditions that are major risk factors for neuropathology. One such type of neuropathology is evident on Magnetic Resonance Imaging (MRI) as areas of hyperintensity in the white matter of the brain. These WMH become increasingly common with advanced age and can be quite extensive without producing gross neurological symptoms. There is, however, evidence that WMH are associated with cognitive decrements. It is thus possible that some of the cognitive decline commonly attributed to """"""""normal"""""""" aging is instead the result of WMH. The study proposed here will examine whether WMH are associated with decrements in cognitive processes thought to be sensitive to normal aging. The study will recruit 150 older persons of the type commonly used in cognitive-aging studies; community-dwelling college-educated individuals 70-85 years old. Fifty college students will be recruited as a comparison group. The older subjects will receive an MRI that will be analyzed with a semi-automated quantitative segmentation software to determine the volume of WMH present. Both old and young subjects will be given tasks designed to examine three fundamental mechanisms currently theorized to underlie the cognitive decrements of aging; decreased working-memory capacity, cognitive slowing and decreased inhibition. The MRI and cognitive testing will be repeated two and a half years later in the older subjects to determine whether increases in WMH volume are associated with a further cognitive decline. This study will also examine the nature and severity of the cognitive decrements present in those older person who show no evidence of neuropathology on their MRIs. Thus, this project will both investigate whether WMH may be responsible for much of the cognitive decline typically attributed to normal aging and will examine the cognitive status of older persons with no MRI evidence of brain pathology.

Agency
National Institute of Health (NIH)
Institute
National Institute on Aging (NIA)
Type
Research Project (R01)
Project #
5R01AG014051-04
Application #
6163776
Study Section
Human Development and Aging Subcommittee 3 (HUD)
Program Officer
Wagster, Molly V
Project Start
1997-04-15
Project End
2002-02-28
Budget Start
2000-03-01
Budget End
2001-02-28
Support Year
4
Fiscal Year
2000
Total Cost
$255,686
Indirect Cost
Name
University of Pittsburgh
Department
Psychiatry
Type
Schools of Medicine
DUNS #
053785812
City
Pittsburgh
State
PA
Country
United States
Zip Code
15213
Nebes, Robert D; Pollock, Bruce G; Perera, Subashan et al. (2012) The greater sensitivity of elderly APOE ?4 carriers to anticholinergic medications is independent of cerebrovascular disease risk. Am J Geriatr Pharmacother 10:185-92
Nebes, Robert D; Meltzer, Carolyn C; Whyte, Ellen M et al. (2006) The relation of white matter hyperintensities to cognitive performance in the normal old: education matters. Neuropsychol Dev Cogn B Aging Neuropsychol Cogn 13:326-40
Nebes, R D; Pollock, B G; Meltzer, C C et al. (2005) Serum anticholinergic activity, white matter hyperintensities, and cognitive performance. Neurology 65:1487-9
Luedecking-Zimmer, Erin; DeKosky, Steven T; Nebes, Robert et al. (2003) Association of the 3' UTR transcription factor LBP-1c/CP2/LSF polymorphism with late-onset Alzheimer's disease. Am J Med Genet B Neuropsychiatr Genet 117B:114-7
Nebes, Robert D; Reynolds 3rd, Charles F; Boada, Fernando et al. (2002) Longitudinal increase in the volume of white matter hyperintensities in late-onset depression. Int J Geriatr Psychiatry 17:526-30
Aizenstein, H J; Nebes, R D; Meltzer, C C et al. (2002) The relation of White Matter Hyperintensities to implicit learning in healthy older adults. Int J Geriatr Psychiatry 17:664-9
Luedecking-Zimmer, Erin; DeKosky, Steven T; Chen, Qi et al. (2002) Investigation of oxidized LDL-receptor 1 (OLR1) as the candidate gene for Alzheimer's disease on chromosome 12. Hum Genet 111:443-51
Nebes, R D; Vora, I J; Meltzer, C C et al. (2001) Relationship of deep white matter hyperintensities and apolipoprotein E genotype to depressive symptoms in older adults without clinical depression. Am J Psychiatry 158:878-84