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 magnetic resonance imaging, we found that individual differences in learning and memory were positively associated with LC integrity across a variety of memory tasks in both younger (n = 66) and older adults (n = 228). Moreover, we observed functionally relevant age differences confined to rostral LC. Older adults with a more ‘youth-like’ rostral LC also showed higher memory performance. These findings link non-invasive, in vivo indices of LC integrity to memory in ageing and highlight the role of the LC norepinephrine system in the decline of cognition. Dahl et al. use neuromelanin-sensitive neuroimaging in a cohort of participants spanning ages 25 to 83 and report that ‘youth-like’ rostral locus coeruleus integrity is associated with better memory performance in the elderly.
Abstract Older adults experience difficulties in daily situations that require flexible information selection in the presence of multiple competing sensory inputs, like for instance multi-talker situations. Modulations of rhythmic neural activity in the alpha–beta (8–30 Hz) frequency range in posterior brain areas have been established as a cross-modal neural correlate of selective attention. However, research linking compromised auditory selective attention to changes in rhythmic neural activit...
#1William J. Jagust(HWNI: Helen Wills Neuroscience Institute)H-Index: 140
Technologies for imaging the pathophysiology of Alzheimer disease (AD) now permit studies of the relationships between the two major proteins deposited in this disease — amyloid-β (Aβ) and tau — and their effects on measures of neurodegeneration and cognition in humans. Deposition of Aβ in the medial parietal cortex appears to be the first stage in the development of AD, although tau aggregates in the medial temporal lobe (MTL) precede Aβ deposition in cognitively healthy older people. Whether a...
Last. Marc I. Diamond(UTSW: University of Texas Southwestern Medical Center)H-Index: 52
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Alzheimer’s disease (AD) is characterized by accumulation of tau neurofibrillary tangles (NFTs) and, according to the prion model, transcellular propagation of pathological “seeds” may underlie its progression. Staging of NFT pathology with phospho-tau antibody is useful to classify AD and primary age-related tauopathy (PART) cases. The locus coeruleus (LC) shows the earliest phospho-tau signal, whereas other studies suggest that pathology begins in the transentorhinal/entorhinal cortices (TRE/E...
It has been known for decades that degeneration of the locus coeruleus (LC), the major noradrenergic nucleus in the brain, occurs in both Alzheimer's disease (AD) and Parkinson's disease (PD), but it was given scant attention. It is now recognized that hyperphosphorylated tau in the LC is the first detectable AD-like neuropathology in the human brain, α-synuclein inclusions in the LC represent an early step in PD, and experimental LC lesions exacerbate neuropathology and cognitive/behavioral def...
Last. Emrah Düzel(UCL: University College London)H-Index: 71
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The locus coeruleus (LC) is the principal origin of noradrenaline in the brain. LC integrity varies considerably across healthy older individuals, and is suggested to contribute to altered cognitive functions in aging. Here we test this hypothesis using an incidental memory task that is known to be susceptible to noradrenergic modulation. We used MRI neuromelanin (NM) imaging to assess LC structural integrity and pupillometry as a putative index of LC activation in both younger and older adults....
Last. Robert Howard(UCL: University College London)H-Index: 89
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Abstract The locus coeruleus (LC), the major origin of noradrenergic modulation of the central nervous system, innervates extensive areas throughout the brain and is implicated in a variety of autonomic and cognitive functions. Alterations in the LC-noradrenergic system have been associated with healthy ageing and neuropsychiatric disorders including Parkinson’s disease, Alzheimer’s disease and depression. The last decade has seen advances in imaging the structure and function of the LC, and thi...
#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
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The locus coeruleus (LC), a major origin of noradrenergic projections in the central nervous system (CNS), may serve a critical role in the pathogenesis of neurodegenerative disorders such as Alzheimer's disease (AD) and Parkinson's disease (PD). As such, there is considerable interest to develop magnetic resonance imaging (MRI) techniques to assess the integrity of the LC in vivo. The high neuromelanin content of the LC serves as an endogenous contrast for MRI but existing protocols suffer from...
Abstract null null Current diagnosis of Alzheimer's disease (AD) relies on a combination of neuropsychological evaluations, biomarker measurements and brain imaging. Nevertheless, these approaches are either expensive, invasive or lack sensitivity to early AD stages. The main challenge of ongoing research is therefore to identify early non-invasive biomarkers to diagnose AD at preclinical stage. null Accumulating evidence support the hypothesis that initial degeneration of profound monoaminergic...
Last. Lars Bertram(University of Lübeck)H-Index: 71
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Purpose null The study 'Sex- and gender-sensitive prevention of cardiovascular and metabolic disease in older adults in Germany', the GendAge study, focuses on major risk factors for cardiovascular and metabolic diseases and on the development of major outcomes from intermediate phenotypes in the context of sex and gender differences. It is based on a follow-up examination of a subsample (older group) of the Berlin Aging Study II (BASE-II). null Participants null The GendAge study assessments to...
#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...
BACKGROUND Alzheimer's disease (AD) is characterized by progressive deterioration of cognitive functions and may be preceded by mild cognitive impairment (MCI). Evidence shows changes in pupil and vergence responses related to cognitive processing of visual information. OBJECTIVE Here we test the hypothesis that MCI and AD are associated with specific patterns in vergence and pupil responses. METHODS We employed a visual oddball task. In the distractor condition (80%of the trials), a blue stimul...
BACKGROUND Pathology in the noradrenergic A6 locus coeruleus has not been compared with more rostral dopaminergic A9 substantia nigra and A10 ventral tegmental area, and cholinergic Ch4 basal nucleus and Ch1/2 septal regions in the same cases of Parkinson's disease (PD). OBJECTIVE To determine whether there is a gradient of caudal to rostral cell loss in PD. METHODS Postmortem brains were collected from longitudinally followed donors with PD (n = 14) and aged-matched healthy donors (n = 13), six...
Last. Mara Mather(SC: University of Southern California)H-Index: 68
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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...
Observing Alzheimer's disease (AD) pathological changes in vivo with neuroimaging provides invaluable opportunities to understand and predict the course of disease. Neuroimaging AD biomarkers also allow for real-time tracking of disease-modifying treatment in clinical trials. With recent neuroimaging advances, along with the burgeoning availability of longitudinal neuroimaging data and big-data harmonization approaches, a more comprehensive evaluation of the disease has shed light on the topogra...
Last. Scott E. Counts(MSU: Michigan State University)H-Index: 16
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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...
Although, the clinical variants of Alzheimer's disease (AD) show distinct patterns of cognitive and behavioral decline, disease progression, and neuropathological features, it is unclear if this clinical heterogeneity extends to sleep-wake patterns. Sleep and wake disturbances are frequent in typical AD, often preceding memory loss and negatively impacting the quality of life of patients and caregivers alike. Still, sleep and wake disorders are often misdiagnosed and undertreated in typical AD. ...
#1Carolyn W. Harley(MUN: Memorial University of Newfoundland)H-Index: 38
#2Susan G. Walling(MUN: Memorial University of Newfoundland)H-Index: 10
Last. Gerard M. Martin(MUN: Memorial University of Newfoundland)H-Index: 16
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Braak has described the beginnings of Alzheimer's Disease as occurring in the locus coeruleus. Here we review these pretangle stages and relate their expression to recently described normal features of tau biology. We suggest pretangle tau depends on characteristics of locus coeruleus operation that promote tau condensates. We examine the timeline of pretangle and tangle appearance in locus coeruleus. We find catastrophic loss of locus coeruleus neurons is a late event. The strong relationship b...