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Neurobiol Aging. 2016 Jan;37:117-126. doi: 10.1016/j.neurobiolaging.2015.09.019. Epub 2015 Oct 29.

Neuromelanin marks the spot: identifying a locus coeruleus biomarker of cognitive reserve in healthy aging.

Author information

1
Neuroscience Graduate Program, University of Southern California, Los Angeles, CA, USA. Electronic address: clewett@usc.edu.
2
Department of Psychology, University of Southern California, Los Angeles, CA, USA.
3
Department of Psychology, University of Southern California, Los Angeles, CA, USA; Davis School of Gerontology, University of Southern California, Los Angeles, CA, USA; Department of Psychology, Louisiana State University, Baton Rouge, LA, USA.
4
Davis School of Gerontology, University of Southern California, Los Angeles, CA, USA.
5
Dornsife College of Letters and Sciences, University of Southern California, Los Angeles, CA, USA.
6
Neuroscience Graduate Program, University of Southern California, Los Angeles, CA, USA; Department of Psychology, University of Southern California, Los Angeles, CA, USA; Davis School of Gerontology, University of Southern California, Los Angeles, CA, USA.

Abstract

Leading a mentally stimulating life may build up a reserve of neural and mental resources that preserve cognitive abilities in late life. Recent autopsy evidence links neuronal density in the locus coeruleus (LC), the brain's main source of norepinephrine, to slower cognitive decline before death, inspiring the idea that the noradrenergic system is a key component of reserve (Robertson, I. H. 2013. A noradrenergic theory of cognitive reserve: implications for Alzheimer's disease. Neurobiol. Aging. 34, 298-308). Here, we tested this hypothesis using neuromelanin-sensitive magnetic resonance imaging to visualize and measure LC signal intensity in healthy younger and older adults. Established proxies of reserve, including education, occupational attainment, and verbal intelligence, were linearly correlated with LC signal intensity in both age groups. Results indicated that LC signal intensity was significantly higher in older than younger adults and significantly lower in women than in men. Consistent with the LC-reserve hypothesis, both verbal intelligence and a composite reserve score were positively associated with LC signal intensity in older adults. LC signal intensity was also more strongly associated with attentional shifting ability in older adults with lower cognitive reserve. Together these findings link in vivo estimates of LC neuromelanin signal intensity to cognitive reserve in normal aging.

KEYWORDS:

Aging; Brain reserve; Cognitive reserve; Gender; Locus coeruleus; Norepinephrine; Sex

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