Association of β-Amyloid Burden With Sleep Dysfunction and Cognitive Impairment in Elderly Individuals With Cognitive Disorders

You, Jason; Jones, Erica; Cross, Devon E.; Lyon, Abigail C.; Kang, Hyun-Seung; Newberg, Andrew B.; Lippa, Carol F.

doi:10.1001/jamanetworkopen.2019.13383

Cited by 38 publications

(43 citation statements)

References 48 publications

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“…Thus, sleep problems might be a result of neurodegeneration. However, the decline in sleep quality is also associated with an increase in beta amyloid deposits (a hallmark of AD) leading to faster disease progression 51,57 . Increased beta amyloid levels in the brain impair slow-wave sleep leading to sleep problems 58,59 , thus sleep problems might be a correlate of neurodegeneration.…”

Section: Discussionmentioning

confidence: 99%

Associations between self-reported sleep characteristics and incident mild cognitive impairment: The Heinz Nixdorf Recall Cohort Study

Brachem

Winkler

Tebrügge

et al. 2020

Sci Rep

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Associations of sleep characteristics with mild cognitive impairment (Mci) have been examined in cross-sectional, but rarely in longitudinal studies. incident Mci and sleep characteristics were assessed in 1,890 participants of the first and second follow-up of the Heinz Nixdorf Recall study, a populationbased cohort study in Germany (age at first follow-up 50−80 years, mean follow-up 5.2 years). MCI was assessed with extensive cognitive tests. Sleep questionnaires including pSQi (pittsburgh Sleep Quality index) were used to assess sleep quality, sleep disturbances, time asleep, and time in bed. Relative risks (RR) of developing Mci when exposed to sleep characteristics were assessed in regression models adjusted for sociodemographic and cardiovascular risk factors. poor sleep quality (pSQi > 5) (RR = 1.43, 95% CI: 1.12−1.82, fully adjusted, reference: PSQI ≤ 5) and difficulties initiating sleep (almost nightly versus never) (RR = 1.40, 0.94−2.08) were associated with incident MCI. For time in bed, the risk of MCI was increased for ≤ 5 hours (RR = 2.86, 1.24─6.60, reference:7 to <8 hours). In this longitudinal study with older participants, MCI risk was increased in persons with poor sleep quality, difficulties initiating sleep, and short time in bed. Dementia is a growing public health burden worldwide. In 2013 an estimated 44.35 million persons had a prevalent dementia 1. By 2050 it is expected that this number triples to 135.46 million prevalent dementia cases 2,3. Because no effective causal medical therapies are available for dementia, primary prevention of dementia and of its early precursors is the most promising option currently available to cap the rising prevalence 4,5. Subjects with mild cognitive impairment (MCI) have an increased risk of progression to Alzheimer's disease (AD) and other forms of dementia. Therefore, identification of modifiable risk factors for incident MCI is important, and poor sleep is considered a potential risk factor for cognitive decline and disease progression 6-13. Sleep characteristics were suggested as modifiable risk factors for cognitive decline, for example by influencing hippocampal volume 14,15. Two up-to-date reviews on this relationship indicate an association between cognitive decline and sleep problems, such as poor sleep quality, short or long sleep duration, and sleep disturbances 12,16. However, both reviews concluded that there is still a need for long term prospective studies to ensure that sleep problems precede cognitive decline 12,16. Two recently published cohort studies on sleep characteristics and dementia were not included in these reviews 17,18. Both suggest that self-reported long sleep duration as well as self-reported sleep disturbances increase the risk of dementia. Additionally, Jackowska and Cadar 19 found an association between decreased cognitive function and self-reported long and short sleep duration in their

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Section: Discussionmentioning

confidence: 99%

Associations between self-reported sleep characteristics and incident mild cognitive impairment: The Heinz Nixdorf Recall Cohort Study

Brachem

Winkler

Tebrügge

et al. 2020

Sci Rep

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“…Increased wakefulness and disturbed sleep lead to increased Aβ production and decreased Aβ clearance; additionally, chronic wakefulness increases Aβ aggregation and deposition, and Aβ accumulation results in disturbed sleep. Sleep deprivation increases brain and CSF tau levels and the spread of tau protein aggregates in neural tissues, correlating with decreased nonrapid eye movement (NREM) sleep slow wave activity [256,257].…”

Section: Sleep Disordersmentioning

confidence: 99%

Pharmacogenomics of Cognitive Dysfunction and Neuropsychiatric Disorders in Dementia

Cacabelos

2020

IJMS

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Symptomatic interventions for patients with dementia involve anti-dementia drugs to improve cognition, psychotropic drugs for the treatment of behavioral disorders (BDs), and different categories of drugs for concomitant disorders. Demented patients may take >6–10 drugs/day with the consequent risk for drug–drug interactions and adverse drug reactions (ADRs >80%) which accelerate cognitive decline. The pharmacoepigenetic machinery is integrated by pathogenic, mechanistic, metabolic, transporter, and pleiotropic genes redundantly and promiscuously regulated by epigenetic mechanisms. CYP2D6, CYP2C9, CYP2C19, and CYP3A4/5 geno-phenotypes are involved in the metabolism of over 90% of drugs currently used in patients with dementia, and only 20% of the population is an extensive metabolizer for this tetragenic cluster. ADRs associated with anti-dementia drugs, antipsychotics, antidepressants, anxiolytics, hypnotics, sedatives, and antiepileptic drugs can be minimized by means of pharmacogenetic screening prior to treatment. These drugs are substrates, inhibitors, or inducers of 58, 37, and 42 enzyme/protein gene products, respectively, and are transported by 40 different protein transporters. APOE is the reference gene in most pharmacogenetic studies. APOE-3 carriers are the best responders and APOE-4 carriers are the worst responders; likewise, CYP2D6-normal metabolizers are the best responders and CYP2D6-poor metabolizers are the worst responders. The incorporation of pharmacogenomic strategies for a personalized treatment in dementia is an effective option to optimize limited therapeutic resources and to reduce unwanted side-effects.

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“…To add to this connection, our results demonstrate circadian control of the phagocytosis of Aβ42 in murine macrophages (Figure 1). As peripheral macrophages are models for microglia and also migrate to the brain in the later stages of AD, our findings suggest the disruption of the circadian timing of macrophage/microglia phagocytosis may be a vital component in Aβ42 metabolism, highlighting a potential causative factor in the increase in accumulation of Aβ42 in patients with clock/sleep disturbances 8,13,20,22,25,82,83 .…”

Section: Discussionmentioning

confidence: 74%

“…The clearance of Aβ42, which is inhibited in AD pathology, is essential for a healthy neuronal microenvironment 6,82 . Metabolism of Aβ42 is controlled by the circadian clock in vivo and disruption of oscillations in this rhythm could affect the accumulation of Aβ42 6 .…”

Section: Discussionmentioning

confidence: 99%

Circadian Control of Heparan Sulfate Levels Times Phagocytosis of Amyloid Beta Aggregates

Clark

et al. 2021

Preprint

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SummaryAlzheimer’s Disease (AD) is a neuroinflammatory disease characterized partly by the inability to clear, and subsequent build-up, of amyloid-beta (Aβ). Aβ clearance is regulated by several pathways and has a circadian component. However, the mechanism underlying the circadian clearance of Aβ has not been defined. Myeloid-based phagocytosis, a key mechanism in the metabolism of Aβ, is circadianly-regulated, presenting a potential mechanism for the circadian clearance of Aβ. In this work, we revealed that the phagocytosis of Aβ42 undergoes a daily oscillation that is dependent on the circadian clock. We found the circadian timing of global heparan sulfate proteoglycan (HSPG) biosynthesis was the molecular timer for the clock-controlled phagocytosis of Aβ and that both HSPG binding and Aβ42 aggregation were essential for this oscillation. These data highlight that circadian regulation in immune cells may play a role in the intricate relationship between the circadian clock and AD.Graphical Abstract

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Association of β-Amyloid Burden With Sleep Dysfunction and Cognitive Impairment in Elderly Individuals With Cognitive Disorders

Cited by 38 publications

References 48 publications

Associations between self-reported sleep characteristics and incident mild cognitive impairment: The Heinz Nixdorf Recall Cohort Study

Associations between self-reported sleep characteristics and incident mild cognitive impairment: The Heinz Nixdorf Recall Cohort Study

Pharmacogenomics of Cognitive Dysfunction and Neuropsychiatric Disorders in Dementia

Circadian Control of Heparan Sulfate Levels Times Phagocytosis of Amyloid Beta Aggregates

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