Locus coeruleus integrity is related to tau burden and memory loss in autosomal-dominant Alzheimer's disease

Dahl, Martin J.; Mather, Mara; Werkle‐Bergner, Markus; Kennedy, Briana L.; Guzman, Samuel; Hurth, Kyle; Miller, Carol A.; Qiao, Yuchuan; Shi, Yonggang; Chui, Helena C.; Ringman, John M.

doi:10.1016/j.neurobiolaging.2021.11.006

Cited by 69 publications

(118 citation statements)

References 110 publications

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“…(C) Detailed axial view of TSE template, warped to MNI152 space. (D) TSE template, warped to MNI152 space, overlaid with locus coeruleus meta-mask and pontine reference region from Dahl et al (2021), which were used for calculation of LC contrast ratios.…”

Section: Methodsmentioning

confidence: 99%

“…To compute LC contrast ratios reflecting peak LC intensity relative to that of surrounding tissue, we also extracted intensity values from a central pontine region (Figure 1D). Specifically, we applied the central pontine reference map from Dahl et al (2021) as a mask on individual TSE scans that had been warped to MNI space and extracted the peak intensity value within the masked region.…”

Section: Lc Delineationmentioning

confidence: 99%

“…Dahl et al (2021) meta-map, which was generated by aggregating across published LC maps and thus reflected a plausible LC volume of interest with high agreement across studies. We found high correspondence between hyperintensities on the TSE template and the LC meta-map (Supplementary FigureS1).…”

mentioning

confidence: 99%

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Daily heart rate variability biofeedback training decreases locus coeruleus MRI contrast in younger adults

Bachman

Cole

Yoo

et al. 2022

Preprint

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As an arousal hub region in the brain, the locus coeruleus (LC) has bidirectional connections with the autonomic nervous system. Magnetic resonance imaging (MRI)-based measures of LC structural integrity have been linked to cognition and arousal, but less is known about factors that influence LC structure and function across time. Here, we tested the effects of heart rate variability (HRV) biofeedback, an intervention targeting the autonomic nervous system, on LC MRI contrast and sympathetic activity. Younger and older participants completed daily HRV biofeedback training for five weeks. Those assigned to an experimental condition performed biofeedback involving slow, paced breathing designed to increase heart rate oscillations, whereas those assigned to a control condition performed biofeedback to decrease heart rate oscillations. At the pre- and post-training timepoints, LC contrast was assessed using turbo spin echo MRI scans, and RNA sequencing was used to assess cAMP-responsive element binding protein (CREB)-regulated gene expression in circulating blood cells, an index of sympathetic nervous system signaling. We found that left LC contrast decreased in younger participants in the experimental group, and across younger participants, decreases in left LC contrast were related to the extent to which participants increased their heart rate oscillations during training. Furthermore, decreases in left LC contrast were associated with decreased expression of CREB-associated gene transcripts. On the contrary, there were no effects of biofeedback on LC contrast among older participants in the experimental group. These findings provide novel evidence that in younger adults, HRV biofeedback involving slow, paced breathing can decrease both LC contrast and sympathetic nervous system signaling.

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Section: Methodsmentioning

confidence: 99%

Section: Lc Delineationmentioning

confidence: 99%

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Daily heart rate variability biofeedback training decreases locus coeruleus MRI contrast in younger adults

Bachman

Cole

Yoo

et al. 2022

Preprint

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“…(C) LC map from Dahl et al (2021) shown in pink, overlaid on the TSE template in standard space. Reference map, also from Dahl et al (2021), shown in yellow. (D) Sagittal (left) and coronal (right) views of LC map (pink) overlaid on the TSE template in standard space.…”

Section: Methodsmentioning

confidence: 99%

“…To isolate potential LC voxels on warped TSE scans, we applied the Dahl et al (2021) meta-map as a mask; this mask was selected because it aggregates across many published LC maps. Within the masked region on each scan, we extracted the intensity value and coordinates of the peak-intensity voxel in each slice in the z dimension for left and right LC.…”

Section: Methodsmentioning

confidence: 99%

Associations between locus coeruleus MRI contrast and physiological responses to acute stress in younger and older adults

Bachman¹,

Nashiro²,

Yoo³

et al. 2022

Preprint

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Acute stress robustly activates the brain's noradrenergic system, the hub of which is the locus coeruleus (LC). Recent studies have indicated that structural integrity of the LC, assessed through magnetic resonance imaging (MRI), is associated with better cognitive outcomes in later life. However, no studies have examined whether MRI-assessed LC integrity is related to arousal responses to acute stress in either younger or older adults, despite the LC's documented role in promoting physiological arousal as part of the acute stress response. In this study, 102 younger and 51 older adults completed an acute stress induction task while we assessed multiple measures of physiological arousal (heart rate, breathing rate, systolic and diastolic blood pressure, sympathetic tone, and heart rate variability, HRV). We used turbo spin echo MRI scans to quantify LC MRI contrast as a measure of LC integrity. Using univariate and multivariate approaches, we assessed how LC MRI contrast was associated with arousal at rest and during acute stress reactivity and recovery. We found that in older adults, having higher caudal LC MRI contrast was associated with greater stress-related increases in systolic blood pressure and decreases in HRV, as well as lower HRV during recovery from acute stress. These results suggest that having higher caudal LC integrity in older adulthood is associated with more pronounced physiological responses to acute stress. Further work is needed to confirm these patterns in larger samples of older adults.

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Priorities for research on neuromodulatory subcortical systems in Alzheimer's disease: Position paper from the NSS PIA of ISTAART

Ehrenberg

Kelberman

Liu

et al. 2023

Alzheimer's & Dementia

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The neuromodulatory subcortical system (NSS) nuclei are critical hubs for survival, hedonic tone, and homeostasis. Tau-associated NSS degeneration occurs early in Alzheimer's disease (AD) pathogenesis, long before the emergence of pathognomonic memory dysfunction and cortical lesions. Accumulating evidence supports the role of NSS dysfunction and degeneration in the behavioral and neuropsychiatric manifestations featured early in AD. Experimental studies even suggest that AD-associated NSS degeneration drives brain neuroinflammatory status and contributes to disease progression, including the exacerbation of cortical lesions. Given the important pathophysiologic and etiologic roles that involve the NSS in early AD stages, there is an urgent need to expand our understanding of the mechanisms underlying NSS vulnerability and more precisely detail the clinical progression of NSS changes in AD. Here,

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Locus coeruleus integrity is related to tau burden and memory loss in autosomal-dominant Alzheimer's disease

Cited by 69 publications

References 110 publications

Daily heart rate variability biofeedback training decreases locus coeruleus MRI contrast in younger adults

Daily heart rate variability biofeedback training decreases locus coeruleus MRI contrast in younger adults

Associations between locus coeruleus MRI contrast and physiological responses to acute stress in younger and older adults

Priorities for research on neuromodulatory subcortical systems in Alzheimer's disease: Position paper from the NSS PIA of ISTAART

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