MRI‐assessed locus coeruleus integrity is heritable and associated with multiple cognitive domains, mild cognitive impairment, and daytime dysfunction

Published on Feb 13, 2021in Alzheimers & Dementia17.127
· DOI :10.1002/ALZ.12261
Jeremy A. Elman15
Estimated H-index: 15
(UCSD: University of California, San Diego),
Olivia K. Puckett1
Estimated H-index: 1
(UCSD: University of California, San Diego)
+ 27 AuthorsWilliam S. Kremen71
Estimated H-index: 71
(UCSD: University of California, San Diego)
Source
Abstract
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 impairment (aMCI), and daytime dysfunction. RESULTS Heritability of LCCNR was .48. Participants with aMCI showed greater daytime dysfunction. Lower LCCNR was associated with poorer episodic memory, general verbal fluency, semantic fluency, and processing speed, as well as increased odds of aMCI and greater daytime dysfunction. DISCUSSION Reduced LC integrity is associated with widespread differences across cognitive domains, daytime sleep-related dysfunction, and risk for aMCI. These findings in late-middle-aged adults highlight the potential of MRI-based measures of LC integrity in early identification of AD risk.
References56
Newest
#1Kathy Y. Liu (UCL: University College London)H-Index: 3
#1Kathy Y. Liu (UCL: University College London)H-Index: 10
Last. Lorraine K. TylerH-Index: 88
view all 9 authors...
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 ...
13 CitationsSource
#1Peng Liu (Xi'an Jiaotong University)H-Index: 2
#2Beiyu Zhao (Xi'an Jiaotong University)H-Index: 4
Last. Qiumin Qu (Xi'an Jiaotong University)H-Index: 8
view all 11 authors...
Alzheimer's disease (AD) is the most common age-associated neurodegenerative disease featured by progressive learning and memory deficit, and Abeta was identified as playing a key role in the process of AD and was theorized to be caused by the imbalance of production and clearance. Increasing evidence suggested an association between sleep deprivation and AD. Our recent study found that chronic sleep restriction (CSR) caused cognitive impairment and Abeta accumulation in rats, but the underlinin...
4 CitationsSource
#1Daniel E. Gustavson (UCSD: University of California, San Diego)H-Index: 16
#2Jeremy A. Elman (UCSD: University of California, San Diego)H-Index: 15
Last. William S. Kremen (UCSD: University of California, San Diego)H-Index: 71
view all 10 authors...
Introduction: Predicting risk for Alzheimer's disease when most people are likely still biomarker negative would aid earlier identification. We hypothesized that combining multiple memory tests and scores in middle-aged adults would provide useful, and non-invasive, prediction of 6-year progression to MCI. Methods: We examined 849 men who were cognitively normal at baseline (mean age +/- SD = 55.69 +/- 2.45). Results: California Verbal Learning Test learning trials was the best individual predic...
5 CitationsSource
#1William S. Kremen (UCSD: University of California, San Diego)H-Index: 71
#2Carol E. Franz (UCSD: University of California, San Diego)H-Index: 49
Last. Michael J. Lyons (BU: Boston University)H-Index: 86
view all 3 authors...
The Vietnam Era Twin Study of Aging (VETSA) is a longitudinal behavioral genetic study with a primary focus on cognitive and brain aging in men, particularly early identification of risk for mild cognitive impairment (MCI) and Alzheimer's disease (AD). It comprises a subset of over 1600 twins from the Vietnam Era Twin Registry. Twins live all over the USA. Assessments began when participants were in their 50s. Follow-ups were conducted every 5-6 years, and wave 3 has been completed as of this wr...
2 CitationsSource
#1Matthew J. Betts (Otto-von-Guericke University Magdeburg)H-Index: 31
#1Matthew J. Betts (Otto-von-Guericke University Magdeburg)H-Index: 6
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
#1Jason C. You (Thomas Jefferson University)H-Index: 5
#2Erica Jones (Thomas Jefferson University Hospital)H-Index: 1
Last. Carol F. Lippa (Thomas Jefferson University Hospital)H-Index: 50
view all 7 authors...
Importance Evidence shows that sleep dysfunction and β-amyloid (Aβ) deposition work synergistically to impair brain function in individuals with normal cognition, increasing the risk of developing dementia later in life. However, whether Aβ continues to play an integral role in sleep dysfunction after the onset of cognitive decline in individuals with dementia is unclear. Objective To determine whether Aβ deposition in the brain is associated with subjective measures of sleep quality and cogniti...
3 CitationsSource
#1Jun Oh (University of California, Berkeley)H-Index: 3
#2Rana Eser (University of California, Berkeley)H-Index: 5
Last. Lea T. GrinbergH-Index: 62
view all 19 authors...
Abstract Introduction Sleep-wake disturbances are a common and early feature in Alzheimer's disease (AD). The impact of early tau pathology in wake-promoting neurons (WPNs) remains unclear. Methods We performed stereology in postmortem brains from AD individuals and healthy controls to identify quantitative differences in morphological metrics in WPNs. Progressive supranuclear palsy (PSP) and corticobasal degeneration were included as disease-specific controls. Results The three nuclei studied a...
23 CitationsSource
#1Martin J. Dahl (MPG: Max Planck Society)H-Index: 5
#2Mara Mather (SC: University of Southern California)H-Index: 67
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: 31
#1Matthew J. Betts (Otto-von-Guericke University Magdeburg)H-Index: 6
Last. Dorothea Hämmerer (UCL: University College London)H-Index: 15
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
#1Mark Sanderson-Cimino (UCSD: University of California, San Diego)H-Index: 6
#2Matthew S. Panizzon (UCSD: University of California, San Diego)H-Index: 35
Last. William S. Kremen (UCSD: University of California, San Diego)H-Index: 71
view all 9 authors...
OBJECTIVE: Processing Speed (PS) is an important domain in cognitive aging that is characterized by multiple related but nonidentical abilities. Few studies have directly investigated the relationships among PS measures, and none have used genetically informed methods. In this study, we examined the relationship between measures of PS at up to two time points during middle age. METHOD: We examined data from 1,262 middle-aged men when the sample was at a mean age of 56 and a mean age 62 years. Pa...
1 CitationsSource
Cited By0
Newest