Tau-driven degeneration of sleep- and wake-regulating neurons in Alzheimer’s disease

Lew, Caroline; Petersen, Cathrine; Neylan, Thomas C.; Grinberg, Lea T.

doi:10.1016/j.smrv.2021.101541

Cited by 42 publications

(37 citation statements)

References 103 publications

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“…We also hypothesized that the decrease in homeostatic sleep drive observed in patients with PSP may have been associated with degeneration of subcortical sleep-promoting nuclei in the setting of spared wake-promoting nuclei. 44 Given that quantitative data on pathological changes in subcortical sleep-promoting neurons in tauopathies is limited, further evaluation is warranted. 42,44,45…”

Section: Discussionmentioning

confidence: 99%

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Subcortical Neuronal Correlates of Sleep in Neurodegenerative Diseases

Walsh

Ranasinghe

et al. 2022

JAMA Neurol

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IMPORTANCESleep disturbance is common among patients with neurodegenerative diseases. Examining the subcortical neuronal correlates of sleep disturbances is important to understanding the early-stage sleep neurodegenerative phenomena.OBJECTIVES To examine the correlation between the number of important subcortical wake-promoting neurons and clinical sleep phenotypes in patients with Alzheimer disease (AD) or progressive supranuclear palsy (PSP).

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Section: Discussionmentioning

confidence: 99%

“…44 Given that quantitative data on pathological changes in subcortical sleep-promoting neurons in tauopathies is limited, further evaluation is warranted. 42,44,45…”

Section: Discussionmentioning

confidence: 99%

Subcortical Neuronal Correlates of Sleep in Neurodegenerative Diseases

Walsh

Ranasinghe

et al. 2022

JAMA Neurol

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“…73 A combination of early tau-associated dysregulation and degeneration of the noradrenergic, orexinergic, histaminergic, and basal forebrain cholinergic systems, all critical nodes in the ascending arousal network that organizes the sleep-wake cycle, contributes to sleep disturbances in AD. 19,[74][75][76][77][78][79][80][81][82] Sleep disturbances precede memory decline in a significant portion of AD patients. Even during the early stages, these disturbances may also contribute to diminished sleep-dependent brain maintenance, which, in turn, exacerbates the propagation of AD protein hallmarks creating a positive feedback loop.…”

Section: Clinical Assessmentmentioning

confidence: 99%

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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“…Epidemiological studies have reported strong associations between reduced self-reported sleep duration and cognitive impairment in the elderly [8]. Research suggests that sleep behavior is intricately linked to amyloid and tau accumulation, the two main neuropathologies implicated in AD [15, 22, 23, 9, 11]. While many interesting open questions remain about potential bidirectional causal connections between sleep and AD, nonetheless sleep metrics have emerged as promising candidates for noninvasive biomarkers for AD [20].…”

Section: Introductionmentioning

confidence: 99%

“…For the high-CASI group, the top 7 transformer features(1,2,5,9,14,17,22), which contain less TST information, receive more attention from the model 6. out of the top 7 transformer features (1, 2, 9, 14, 17, 22) contain sleep efficiency information.…”

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confidence: 99%

A transformer model for predicting cognitive impairment from sleep

Song

Malekzadeh

Saxena

et al. 2022

Preprint

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Sleep disturbances are known to be aggravated with normal aging. Additionally, sleep disruptions have a potentially bidirectional causal relationship with dementia due to neurodegenerative diseases like Alzheimer’s disease. Predictive techniques that can automatically detect cognitive impairment from an individual’s sleep data have broad clinical and biological significance. Here, we present a deep learning approach based on a transformer architecture to predict cognitive status from sleep electroencephalography (EEG) data. This work uses data from N = 1, 502 subjects from the Multi-Ethnic Study of Atherosclerosis (MESA) cohort. Our transformer model achieves 70.22% accuracy at the binary classification task for distinguishing cognitively normal and impaired subjects based on their sleep EEG. Our method outperforms traditional feature handcrafting, which has an overall accuracy of 57.61% for the same task. We use a sparse regression model to understand and interpret the information captured by each learned feature from our transformer model. To our knowledge, this is the first effort to use deep learning to predict cognitive impairment from sleep metrics.

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Tau-driven degeneration of sleep- and wake-regulating neurons in Alzheimer’s disease

Cited by 42 publications

References 103 publications

Subcortical Neuronal Correlates of Sleep in Neurodegenerative Diseases

Subcortical Neuronal Correlates of Sleep in Neurodegenerative Diseases

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

A transformer model for predicting cognitive impairment from sleep

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