title: Neuromelanin marks the spot: identifying a locus coeruleus biomarker of cognitive reserve in healthy aging.
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.
authors.affiliation: Neuroscience Graduate Program, University of Southern California, Los Angeles, CA, USA. Electronic address: clewett@usc.edu.
authors.forename: David V
authors.initials: DV
authors.lastname: Clewett
authors.affiliation: Department of Psychology, University of Southern California, Los Angeles, CA, USA.
authors.forename: Tae-Ho
authors.initials: TH
authors.lastname: Lee
authors.affiliation: 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.
authors.forename: Steven
authors.initials: S
authors.lastname: Greening
authors.affiliation: Davis School of Gerontology, University of Southern California, Los Angeles, CA, USA.
authors.forename: Allison
authors.initials: A
authors.lastname: Ponzio
authors.affiliation: Dornsife College of Letters and Sciences, University of Southern California, Los Angeles, CA, USA.
authors.forename: Eshed
authors.initials: E
authors.lastname: Margalit
authors.affiliation: 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.
authors.forename: Mara
authors.initials: M
authors.lastname: Mather
mesh_terms: D000293:Adolescent; D000328:Adult; D000375:Aging / Q000502:physiology / Q000523:psychology*; D058245:Cognitive Reserve / Q000502:physiology*; D005260:Female; D006801:Humans; D008125:Locus Coeruleus / Q000033:anatomy & histology* / Q000502:physiology*; D008279:Magnetic Resonance Imaging / Q000379:methods*; D008297:Male; D008543:Melanins; D008875:Middle Aged; D059906:Neuroimaging / Q000379:methods*; D009638:Norepinephrine / Q000502:physiology; D012727:Sex Characteristics; D055815:Young Adult
chemical_list: D008543:Melanins; C014121:neuromelanin; D009638:Norepinephrine
keywords: Aging; Brain reserve; Cognitive reserve; Gender; Locus coeruleus; Norepinephrine; Sex