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. 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.

Emotional arousal and recognition memory are differentially reflected in pupil diameter responses during emotional memory for negative events in younger and older adults

“…Studies in humans, rats as well as primates suggest that a reduction of noradrenergic modulation during ageing can be relevant for altered cognitive functions (Arnsten and Golman-Rakic, 1985;Clewett et al, 2016;Mann, 1983), including memory for negative emotional events (Luo et al, 2015). On the other hand, imaging studies which show increased prefrontal and decreased amygdala activation during negative events in older adults suggest that older adults actively downregulate their arousal response to negative events (see Mather, 2016 for a review).…”

The Locus Coeruleus: Essential for Maintaining Cognitive Function and the Aging Brain

“…There is growing evidence that, in later life, individual differences in LC integrity relate to cognitive abilities (e.g., [26, 27]). In the Rush Memory and Aging Project, older participants without diagnosed dementia upon enrollment completed on average about six years of annual cognitive testing before they died [6].…”

The Affective Neuroscience of Aging

“…In a postmortem study, neuronal density in the LC was more strongly correlated with cognitive decline in the few years right before death than neuronal integrity in the ventral segmental area, substantial nigra, or dorsal raphe nucleus (Wilson et al, 2013). In vivo, LC integrity (as assessed by structural imaging optimized to show the LC neuromelanin deposits) is correlated with verbal IQ scores (Clewett et al, in preparation). In addition, higher levels of cerebrospinal fluid noradrenaline are associated with poorer cognitive performance (Wang et al, 2013).…”