Noradrenergic-dependent functions are associated with age-related locus coeruleus signal intensity differences

Published on Apr 6, 2020in Nature Communications12.121
· DOI :10.1038/S41467-020-15410-W
Kathy Y. Liu3
Estimated H-index: 3
(UCL: University College London),
Kathy Y. Liu10
Estimated H-index: 10
(UCL: University College London)
+ 6 AuthorsLorraine K. Tyler88
Estimated H-index: 88
Sources
Abstract
The locus coeruleus (LC), the origin of noradrenergic modulation of cognitive and behavioral function, may play an important role healthy ageing and in neurodegenerative conditions. We investigated the functional significance of age-related differences in mean normalized LC signal intensity values (LC-CR) in magnetization-transfer (MT) images from the Cambridge Centre for Ageing and Neuroscience (Cam-CAN) cohort - an open-access, population-based dataset. Using structural equation modelling, we tested the pre-registered hypothesis that putatively noradrenergic (NA)-dependent functions would be more strongly associated with LC-CR in older versus younger adults. A unidimensional model (within which LC-CR related to a single factor representing all cognitive and behavioral measures) was a better fit with the data than the a priori two-factor model (within which LC-CR related to separate NA-dependent and NA-independent factors). Our findings support the concept that age-related reduction of LC structural integrity is associated with impaired cognitive and behavioral function. Alterations of locus coeruleus signal intensity have been associated with functional changes in health and disease. Here, the authors tested a pre-registered hypothesis on a large number of subjects as part of the Cam-CAN consortium.
📖 Papers frequently viewed together
50 Citations
201911.34Brain
68 Citations
33 Citations
References60
Newest
#1Matthew J. Betts (Otto-von-Guericke University Magdeburg)H-Index: 6
#1Matthew J. Betts (Otto-von-Guericke University Magdeburg)H-Index: 31
Last. Emrah Düzel (UCL: University College London)H-Index: 71
view all 8 authors...
Abstract Introduction This study aimed to assess how interindividual differences in locus coeruleus (LC) magnetic resonance imaging (MRI) contrast relate to cerebrospinal fluid (CSF) biomarkers of Alzheimer's disease (AD). Methods LC MRI contrast was quantified in 73 individuals from the DZNE Longitudinal Cognitive Impairment and Dementia Study (DELCODE) study comprising 25 healthy elderly adults and 21 individuals with subjective cognitive decline, 16 with mild cognitive impairment, and 11 part...
20 CitationsSource
#1Martin J. Dahl (MPG: Max Planck Society)H-Index: 5
#2Mara Mather (SC: University of Southern California)H-Index: 68
Last. Markus Werkle-Bergner (MPG: Max Planck Society)H-Index: 29
view all 7 authors...
For decades, research into memory decline in human cognitive ageing has focused on neocortical regions, the hippocampus and dopaminergic neuromodulation. Recent findings indicate that the locus coeruleus (LC) and noradrenergic neuromodulation may also play an important role in shaping memory development in later life. However, technical challenges in quantification of LC integrity have hindered the study of LC–cognition associations in humans. Using high-resolution, neuromelanin-sensitive magnet...
33 CitationsSource
#1Matthew J. Betts (Otto-von-Guericke University Magdeburg)H-Index: 6
#1Matthew J. Betts (Otto-von-Guericke University Magdeburg)H-Index: 31
Last. Dorothea Hämmerer (UCL: University College London)H-Index: 16
view all 42 authors...
Pathological alterations to the locus coeruleus, the major source of noradrenaline in the brain, are histologically evident in early stages of neurodegenerative diseases. Novel MRI approaches now provide an opportunity to quantify structural features of the locus coeruleus in vivo during disease progression. In combination with neuropathological biomarkers, in vivo locus coeruleus imaging could help to understand the contribution of locus coeruleus neurodegeneration to clinical and pathological ...
68 CitationsSource
#1Susanne Schweizer (Cognition and Brain Sciences Unit)H-Index: 17
#2Jason Stretton (Cognition and Brain Sciences Unit)H-Index: 23
Last. Tim Dalgleish (Cognition and Brain Sciences Unit)H-Index: 87
view all 7 authors...
: Human older age ushers in functional decline across the majority of cognitive domains. A notable exception seems to be affective processing, with older people reporting higher levels of emotional well-being. Here we evaluated age-related changes in emotional reactivity and regulation in a representative subsample (N = 104; age range: 23-88 years) of the population-derived Cambridge Centre for Ageing and Neuroscience cohort. Performance on a film-based emotion reactivity and regulation task in ...
4 CitationsSource
#1Anne Maass (HWNI: Helen Wills Neuroscience Institute)H-Index: 23
#2David Berron (Otto-von-Guericke University Magdeburg)H-Index: 17
Last. William J. Jagust (HWNI: Helen Wills Neuroscience Institute)H-Index: 140
view all 13 authors...
Alzheimer's disease researchers have been intrigued by the selective regional vulnerability of the brain to amyloid-β plaques and tau neurofibrillary tangles. Post-mortem studies indicate that in ageing and Alzheimer's disease tau tangles deposit early in the transentorhinal cortex, a region located in the anterior-temporal lobe that is critical for object memory. In contrast, amyloid-β pathology seems to target a posterior-medial network that subserves spatial memory. In the current study, we t...
33 CitationsSource
#1Sara J. Weston (UO: University of Oregon)H-Index: 10
#2Stuart J. Ritchie ('KCL': King's College London)H-Index: 32
Last. Andrew K. Przybylski (University of Oxford)H-Index: 30
view all 4 authors...
Secondary data analysis, or the analysis of preexisting data, provides a powerful tool for the resourceful psychological scientist. Never has this been more true than now, when technological advanc...
26 CitationsSource
#1Kathy Y. Liu (UCL: University College London)H-Index: 10
#2Julio Acosta-Cabronero (UCL Institute of Neurology)H-Index: 29
Last. Dorothea Hämmerer (Otto-von-Guericke University Magdeburg)H-Index: 1
view all 12 authors...
Abstract The locus coeruleus (LC), the major origin of noradrenergic modulation of the central nervous system, may play an important role in neuropsychiatric disorders including Parkinson's disease and Alzheimer's disease. The pattern of age-related change of the LC across the life span is unclear. We obtained normalized, mean LC signal intensity values, that is, contrast ratios (CRs), from magnetization transfer–weighted images to investigate the relationship between LC CR and age in cognitivel...
35 CitationsSource
#1Dennis Chan (University of Cambridge)H-Index: 24
#2Meredith A. Shafto (Cognition and Brain Sciences Unit)H-Index: 17
Last. Richard N. Henson (Cognition and Brain Sciences Unit)H-Index: 101
view all 7 authors...
Abstract This study tested the hypothesis that mid-life intellectual, physical, and social activities contribute to cognitive reserve (CR). Two hundred five individuals (196 with magnetic resonance imaging) aged 66–88 years from the Cambridge Centre for Ageing and Neuroscience ( www.cam-can.com ) were studied, with cognitive ability and structural brain health measured as fluid IQ and total gray matter volume, respectively. Mid-life activities (MAs) were measured using the Lifetime of Experience...
22 CitationsSource
#1Kamen A. Tsvetanov (University of Cambridge)H-Index: 14
#2Zheng Ye (CAS: Chinese Academy of Sciences)H-Index: 29
Last. James B. Rowe (University of Cambridge)H-Index: 78
view all 8 authors...
Inhibitory control requires precise regulation of activity and connectivity within multiple brain networks. Previous studies have typically evaluated age-related changes in regional activity or changes in interregional interactions. Instead, we test the hypothesis that activity and connectivity make distinct, complementary contributions to performance across the life span and the maintenance of successful inhibitory control systems. A representative sample of healthy human adults in a large, pop...
31 CitationsSource
#1Susanne M. M. de Mooij (UvA: University of Amsterdam)H-Index: 4
#2Richard N. Henson (Cognition and Brain Sciences Unit)H-Index: 101
Last. Rogier A. Kievit (Cognition and Brain Sciences Unit)H-Index: 32
view all 4 authors...
It is well established that brain structures and cognitive functions change across the life span. A long-standing hypothesis called “age differentiation” additionally posits that the relations between cognitive functions also change with age. To date, however, evidence for age-related differentiation is mixed, and no study has examined differentiation of the relationship between brain and cognition. Here we use multigroup structural equation models (SEMs) and SEM trees to study differences withi...
29 CitationsSource
Cited By13
Newest
#1Orssatto Lbr (QUT: Queensland University of Technology)H-Index: 1
#2David N. Borg (Griffith University)H-Index: 6
Last. Gabriel S. Trajano (QUT: Queensland University of Technology)H-Index: 11
view all 0 authors...
Age-related deterioration within both motor neurones and monoaminergic systems should theoretically reduce neuromodulation by weakening motor neuronal persistent inward current (PIC) strength. However, this assumption remains untested. Surface electromyographic signals were collected using two 32-channel electrode matrices placed on soleus and tibialis anterior of 25 older adults (70{+/-}4years) and 17 young adults (29{+/-}5 years) to investigate motor unit discharge behaviours. Participants per...
Source
#1Andrew K. Evans (Stanford University)H-Index: 6
#2Heui Hye Park (Stanford University)H-Index: 1
Last. Mehrdad Shamloo (Stanford University)H-Index: 40
view all 0 authors...
Abstract null null The locus coeruleus (LC) provides the primary noradrenergic input to the forebrain and hippocampus, and may be vulnerable to degeneration and contribute to age-related cognitive decline and neuroinflammation. Additionally, inhibition of noradrenergic transmission by brain-permeable beta-blockers could exacerbate cognitive impairment. This study examined effects of age and acute beta-blocker administration on LC and hippocampus pathology, neuroinflammation and learning and memo...
Source
#1Altamash Hassan (NU: Northwestern University)H-Index: 2
#2Fajardo Me (NU: Northwestern University)
Last. Gregory E. P. Pearcey (NU: Northwestern University)H-Index: 1
view all 0 authors...
Aging is a natural process that causes alterations in the neuromuscular system, which contribute to weakness and reduced quality of life. Reduced firing rates of individual motor units (MUs) likely contribute to weakness, but the mechanisms underlying reduced firing rates are not clear. Persistent inward currents (PICs) are crucial for the initiation, gain control, and maintenance of motoneuron firing, and are directly proportional to the level of monoaminergic input. Since the concentration of ...
Source
#1Mara Mather (SC: University of Southern California)H-Index: 68
Many believe that engaging in novel and mentally challenging activities promotes brain health and prevents Alzheimer's disease in later life. However, mental stimulation may also have risks as well as benefits. As neurons release neurotransmitters, they often also release amyloid peptides and tau proteins into the extracellular space. These by-products of neural activity can aggregate into the tau tangle and amyloid plaque signatures of Alzheimer's disease. Over time, more active brain regions a...
1 CitationsSource
#1Filippo Sean Giorgi (UniPi: University of Pisa)H-Index: 27
#2Alessandro GalganiH-Index: 3
Last. Francesco Fornai (UniPi: University of Pisa)H-Index: 59
view all 5 authors...
The hypothalamus and Locus Coeruleus (LC) share a variety of functions, as both of them take part in the regulation of the sleep/wake cycle and in the modulation of autonomic and homeostatic activities. Such a functional interplay takes place due to the dense and complex anatomical connections linking the two brain structures. In Alzheimer's disease (AD), the occurrence of endocrine, autonomic and sleep disturbances have been associated with the disruption of the hypothalamic network; at the sam...
Source
#1Shelby L. Bachman (SC: University of Southern California)H-Index: 5
#2Martin J. Dahl (MPG: Max Planck Society)H-Index: 5
Last. Mara Mather (SC: University of Southern California)H-Index: 68
view all 8 authors...
Abstract There is growing evidence that neuronal integrity of the noradrenergic locus coeruleus (LC) is important for later-life cognition. Less understood is how LC integrity relates to brain correlates of cognition, such as brain structure. Here, we examined the relationship between cortical thickness and a measure reflecting LC integrity in older (n = 229) and younger adults (n = 67). Using a magnetic resonance imaging sequence which yields high signal intensity in the LC, we assessed the con...
Source
#1Sarah C. Kelly (MSU: Michigan State University)H-Index: 2
#2Peter T. Nelson (UK: University of Kentucky)H-Index: 78
Last. Scott E. Counts (MSU: Michigan State University)H-Index: 16
view all 3 authors...
Locus coeruleus (LC) neurodegeneration is associated with cognitive deterioration during the transition from normal cognition to mild cognitive impairment (MCI) and Alzheimer disease (AD). However, the extent to which LC degenerative processes differentiate cognitively normal, "resilient" subjects bearing a high AD pathological burden from those with MCI or AD remains unclear. We approached this problem by quantifying the number of LC neurons and the percentage of LC neurons bearing AT8 tau path...
Source
#1Shubir Dutt (SC: University of Southern California)H-Index: 10
#2Yanrong Li (UCI: University of California, Irvine)H-Index: 1
view all 5 authors...
Neuropathological research suggests the tau pathology of Alzheimer's disease may originate in brainstem nuclei, yet it remains unknown whether tau-mediated degeneration of brainstem nuclei influences cognitive impairment in prodromal Alzheimer's disease. The present study examined cognitive domains impacted in prodromal Alzheimer's disease and brainstem substructure volume in cognitively normal older adults (n = 814) and those with mild cognitive impairment (n = 542). Subsamples of cognitively n...
Source
#1Jeremy A. Elman (UCSD: University of California, San Diego)H-Index: 15
#2Olivia K. Puckett (UCSD: University of California, San Diego)H-Index: 1
Last. William S. Kremen (UCSD: University of California, San Diego)H-Index: 70
view all 30 authors...
INTRODUCTION The locus coeruleus (LC) undergoes extensive neurodegeneration in early Alzheimer's disease (AD). The LC is implicated in regulating the sleep-wake cycle, modulating cognitive function, and AD progression. METHODS Participants were 481 men (ages 62 to 71.7) from the Vietnam Era Twin Study of Aging. LC structural integrity was indexed by neuromelanin-sensitive magnetic resonance imaging (MRI) contrast-to-noise ratio (LCCNR ). We examined LCCNR , cognition, amnestic mild cognitive imp...
Source
#1Jennifer A. Ross (Drexel University)H-Index: 4
#2Elisabeth J. Van Bockstaele (Drexel University)H-Index: 61
Arousal may be understood on a spectrum, with excessive sleepiness, cognitive dysfunction, and inattention on one side, and hypervigilance, panic, and psychosis on the other side of being in a wakeful state. However, historically, the concepts of arousal and stress have been difficult to define as measurable experimental variables. Divergent efforts to study these subjects have given rise to several disciplines, including neurobiology, neuroendocrinology, and cognitive neuroscience. We discuss t...
1 CitationsSource