ArticleNeurology2013
Neural reserve, neuronal density in the locus ceruleus, and cognitive decline.
Article in Neurology, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 176 papers.
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Who cites it
176 citing papers in PubMed, 289 citations in OpenAlex.
- Daily biofeedback to modulate heart rate oscillations affects structural volume in hippocampal subregions targeted by the locus coeruleus in older adults but not younger adults.Neurobiology of aging · 2023Trial
- Daily heart rate variability biofeedback training decreases locus coeruleus MRI contrast in younger adults in a randomized clinical trial.International journal of psychophysiology : official journal of the International Organization of Psychophysiology · 2023Trial
- A phase II study repurposing atomoxetine for neuroprotection in mild cognitive impairment.Brain : a journal of neurology · 2022Trial
- Attributable risk of Alzheimer's dementia attributed to age-related neuropathologies.Annals of neurology · 2019Trial
- The Effect of Integrated Aerobic and Cognitive Training (Activ4Brain) on Cognition and Neurophysiology in Older Adults: Protocol for a Controlled Trial.JMIR research protocols · 2026Article
- Molecular programs in human locus coeruleus link APOE and neuromelanin to Alzheimer's vulnerability.Acta neuropathologica · 2026Article
- Pathogenic tau in the mouse locus coeruleus produces noradrenergic hyperactivity and neuropsychiatric phenotypes reminiscent of early Alzheimer's disease.Molecular psychiatry · 2026Article
- Article
- Locus Coeruleus as a Master Regulator of Diverse Functions in the Central Nervous System: Its Relevance in Ageing and Neurodegenerative Disorders.Annals of neurosciences · 2026Review
- Vulnerability of locus coeruleus connections to aging and Alzheimer's disease.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2026Article
- Neuromodulation of excitation-inhibition balance in dementia with lewy bodies: a translational framework.Journal of neural transmission (Vienna, Austria : 1996) · 2026Review
- Noradrenergic infraslow rhythm during sleep is the critical link between heart-rate dynamics and memory consolidation.bioRxiv : the preprint server for biology · 2026Article
- Acupuncture-induced changes in locus coeruleus connectivity and memory improvement in patients with amnestic cognitive impairment.IBRO neuroscience reports · 2026Article
- Locus coeruleus degeneration is associated with cortical tau deposition and cognitive decline in older adults at familial risk of Alzheimer's disease.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2026Article
- Electroencephalography, pupillometry, and behavioral evidence for locus coeruleus-noradrenaline system related tonic hyperactivity in older adults.Neurobiology of aging · 2026Article
- Wake-promoting neuromodulators in Alzheimer's disease: Implications for sleep and brain clearance.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2026Review
- Sex and life experience shape locus coeruleus pretangle tau pathology.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2026Article
- Sex differences in neuromodulatory subcortical systems and their implications for Alzheimer's disease.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2026Review
- Functional assessments of short-term spatial memory in the Dog Aging Project identify strong associations with age that are not moderated by body mass.GeroScience · 2026Article
- Pathogenic tau in the mouse locus coeruleus produces noradrenergic hyperactivity and neuropsychiatric phenotypes reminiscent of early Alzheimer's disease.bioRxiv : the preprint server for biology · 2026Article
116 more citing papers are in PubMed but not listed here.
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Authors and funding
8 authors at 1 institution in 1 country.
Funding
Abstract
objectiveTo test the hypothesis that higher neuronal density in brainstem aminergic nuclei contributes to neural reserve.
methodsParticipants are 165 individuals from the Rush Memory and Aging Project, a longitudinal clinical-pathologic cohort study. They completed a mean of 5.8 years of annual evaluations that included a battery of 19 cognitive tests from which a previously established composite measure of global cognition was derived. Upon death, they had a brain autopsy and uniform neuropathologic examination that provided estimates of the density of aminergic neurons in the locus ceruleus, dorsal raphe nucleus, substantia nigra, and ventral tegmental area plus summary measures of neuronal neurofibrillary tangles and Lewy bodies from these nuclei and medial temporal lobe and neocortex.
resultsNeuronal densities in each nucleus were approximately normally distributed. In separate analyses, higher neuronal density in each nucleus except the ventral tegmental area was associated with slower rate of cognitive decline, but when modeled together only locus ceruleus neuronal density was related to cognitive decline (estimate = 0.003, SE = 0.001, p < 0.001). Higher densities of tangles and Lewy bodies in these brainstem nuclei were associated with faster cognitive decline even after controlling for pathologic burden elsewhere in the brain. Locus ceruleus neuronal density, brainstem tangles, and brainstem Lewy bodies had independent associations with rate of cognitive decline. In addition, at higher levels of locus ceruleus neuronal density, the association of Lewy bodies with cognitive decline was diminished.
conclusionDensity of noradrenergic neurons in the locus ceruleus may be a structural component of neural reserve.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.