Impact of Sleep Disturbance on Dementia in Elderly Individuals: Sleep Disturbances and Dementia Risk

Eunji Lim; Bong-Jo Kim; Boseok Cha; So-Jin Lee; Jae-Won Choi; Nuree Kang; Dongyun Lee

doi:10.33069/cim.2024.0036

Chronobiol Med > Volume 7(1); 2025 > Article

Lim, Kim, Cha, Lee, Choi, Kang, and Lee: Impact of Sleep Disturbance on Dementia in Elderly Individuals: Sleep Disturbances and Dementia Risk

Mini-Review

Chronobiology in Medicine 2025;7(1):18-21.

Published online: March 28, 2025

DOI: https://doi.org/10.33069/cim.2024.0036

Impact of Sleep Disturbance on Dementia in Elderly Individuals: Sleep Disturbances and Dementia Risk

Eunji Lim^1,²

, Bong-Jo Kim^2,³

, Boseok Cha^2,³

, So-Jin Lee^2,³

, Jae-Won Choi^2,³

, Nuree Kang³

, Dongyun Lee^1,²

¹Department of Psychiatry, Gyeongsang National University Changwon Hospital, Changwon, Korea

²Department of Psychiatry, Gyeongsang National University College of Medicine, Jinju, Korea

³Department of Psychiatry, Gyeongsang National University Hospital, Jinju, Korea

Corresponding author: Dongyun Lee, MD, PhD, Department of Psychiatry, Gyeongsang National University Changwon Hospital, Gyeongsang National University College of Medicine, 11 Samjeongja-ro, Seongsan-gu, Changwon 51472, Korea.
Tel: 82-55-214-3801, E-mail: yuny0829@gmail.com

Received November 2, 2024 Revised February 24, 2025 Accepted February 24, 2025

This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Researchers are focusing on modifiable risk factors for dementia, including sleep disturbances such as insomnia and sleep-disordered breathing (SDB), which are known to increase the risk of dementia, including Alzheimer’s disease (AD) and vascular dementia (VD). Sleep deprivation promotes amyloid beta (Aβ) accumulation. Inappropriate sleep duration can increase the risk of AD and VD by increasing inflammatory responses. SDB can increase the risk of VD by inducing white matter changes through sleep apnea, promote Aβ formation through hypoxia, and induce hippocampal atrophy to increase the risk of AD. Sleep-related movement disorders (SRMDs) are associated with a 4-fold greater risk of incident all-cause dementia and an increased risk of VD than AD. Studies have indirectly shown that several SRMDs are related to dopaminergic or cholinergic pathways. This review reveals a meaningful association between sleep disturbance and dementia. However, literature regarding the clear pathological mechanism and causal relationship involved is lacking, confirming the need for additional research.

Keywords: Dementia; Sleep initiation and maintenance disorders; Sleep apnea syndromes; Nocturnal myoclonus syndrome; Restless legs syndrome; REM sleep behavior disorder

INTRODUCTION

The number of dementia patients worldwide continues to increase. It is predicted to reach 83.2 million in 2030. The socioeconomic burden imposed by the treatment, management, and prevention of dementia is also increasing [1,2]. Risk factor management is necessary for preventing dementia. The apolipoprotein E (APOE) gene has been reported to be a representative non-modifiable risk factor for dementia [3]. Lifestyle intervention for sleep disturbance has been confirmed to be important as a modifiable risk factor for dementia [1,4]. Sleep disturbances such as insomnia and sleep-disordered breathing (SDB) can affect the formation and removal of amyloid beta (Aβ) or increase the inflammatory response, which can increase the risk of Alzheimer’s disease (AD) and vascular dementia (VD) [5-8]. Sleep disturbances such as sleep-related movement disorders (SRMDs) are commonly observed in patients with Parkinson’s disease (PD), a neurodegenerative disease with a high risk of cognitive decline [9]. In this paper, we examined associations of sleep disturbances, especially insomnia, SDB, SRMDs, with dementia based on previous studies.

INSOMNIA, SDB, SRMDs, AND DEMENTIA RISK

Sleep disturbances include insomnia (sleep-initiation insomnia, sleep duration insomnia), SDB, and SRMD [5,10]. Sleep disturbances are experienced by 25%–44% of AD patients. They can cause psychiatric problems and dementia [7,10-12]. Compared with controls, individuals with sleep problems have 1.55 (95% confidence interval [CI]: 1.25–1.93), 1.65 (95% CI: 1.45–1.86), and 3.78 (95% CI: 2.27–6.30) times greater risks of AD, cognitive impairment, and preclinical AD, respectively [11]. A meta-analysis revealed that individuals with sleep disturbances have a 1.68 (95% CI: 1.51–1.87) times greater risk of cognitive impairment and/or AD [11].

Insomnia

According to 10 years of national U.S. prospective data, sleep-initiation insomnia and sleep-medication usage insomnia can increase the risk of dementia by 1.51 (95% CI: 1.19–1.90) and 1.3 (95% CI: 1.08–1.56) times, respectively [13]. Among sleep disturbances, sleep duration insomnia showed a U-shaped association with poor cognitive performance and the risk of dementia [5,14,15]. In a meta-analysis that examined the relationship between sleep duration and cognitive function in 97,264 people aged 55 years or older, self-reported shorter (≤5 h) and longer (≥9 h) sleep duration was associated with impaired cognitive function [15]. Self-reported short and long sleep increased the risk of poor cognitive function by 1.4 (95% CI: 1.27–1.56) and 1.58 (95% CI: 1.43–1.74) times, respectively [15]. In another meta-analysis, brief sleep duration (≤6 h) and extended sleep duration (≥9 h) showed differences in the risk of dementia in short (≤10 years) and long follow-up (>10 years) periods [16]. Brief sleep duration increased the risk of dementia by 1.46 (95% CI: 1.48–1.77) times in short follow-up studies, but not in long follow-up studies [16]. Extended sleep duration (≥9 h) increased the risk of dementia by 2.2 (95% CI: 1.11–3.3) times and 1.74 (95% CI: 1.3–2.18) times in short and long follow-up studies, respectively [16]. Brief sleep duration was confirmed to be a prodromal symptom of dementia and long sleep duration was confirmed to be a risk factor for dementia.

Sleep-disordered breathing

SDB is characterized by sleep apnea, abnormal respiration, and snoring during sleep. It is present in 70%–80% of dementia patients [5]. A previous meta-analysis on the prevalence of SDB in dementia patients has found that the prevalence of SDB is 89% in AD, 56% in PD, and 16% in Huntington’s disease [6]. Another meta-analysis showed that SDB increased the risk of all cause dementia, AD, and VD through intermittent hypoxia [7]. In a prospective study of patients aged 65 years or older, SDB increased the risk of mild cognitive impairment or dementia by 1.85 (95% CI: 1.11–3.08) times [17]. In a nationwide cohort study, SDB increased the risk of AD by 1.58 (95% CI: 1.013–2.448) times [8].

Sleep-related movement disorders

Among SRMDs, periodic limb movement disorder (PLMD) and restless legs syndrome (RLS) are the most common. Poor sleep quality due to symptoms such as sleep fragmentation, difficulty in sleep initiation, and daytime sleepiness in these patients can increase the risk of dementia [9]. In a longitudinal cohort study, patients with SRMDs had a nearly 4-fold greater risk of incident all-cause dementia (hazard ratio: 3.996, 95% CI: 1.501–5.134, p<0.001) [9]. In elderly individuals aged 65 years or older, the risk of AD is approximately 3 times greater and the risk of VD is approximately 9 times greater [9]. In another study, the risk of all-cause dementia was 1.46 times greater in the presence of SRMDs such as RLS and the risk of VD was greater than that of AD [18].

MECHANISM

Sleep disturbance can increase mRNA expression of proinflammatory cytokines by activating noradrenergic activity, thereby activating inflammatory signaling pathways [19,20]. Inflammation can increase AD risk by increasing the Aβ burden [19]. In addition, sleep disturbance can increase dementia risk by affecting Aβ production and/or clearance in the glymphatic system, which plays a role in waste elimination and distribution of non-wasted compounds in the brain [21-23].

Insomnia

Short sleep duration is associated with acceleration of age-related brain atrophy, especially, hippocampal atrophy, which can promote cognitive decline [24]. Sleep deprivation causes attenuation of clearance of Aβ, which may increase the risk of AD [25,26]. Elevated levels of interleukin-6 and C-reactive protein have been found in both sleep-deprived individuals and long sleepers [27-29], which may increase the risk of AD and VD [30]. In addition, short and long duration sleep may increase the risk of cardiovascular disease [31] and cardiometabolic risk [32], which can increase the risk of cognitive impairment [33]. In particular, vascular risk factors such as obesity, diabetes mellitus, and obstructive sleep apnea are associated with hippocampal size reduction and early development of cognitive impairment [33].

Sleep-disordered breathing

SDB is characterized by sleep apnea. It is associated with a high risk of developing cerebrovascular pathology [5]. In particular, among SDB, obstructive sleep apnea was associated with 2.08 times higher risk of white matter hyperintensity, which could increase the risk of VD [34]. In addition, SDB might be a risk factor for dementia by inducing brain degeneration and affecting brain cortical thickness through hypoxia [35]. Hypoxia can promote Aß formation [36] and induce hippocampal atrophy through oxidative stress and inflammation [37], which may affect cognitive impairment and AD pathology [38,39].

Sleep-related movement disorders

SRMDs such as PLMD and RLS characterized by nocturnal involuntary limb movement can directly affect cognitive decline by causing chronic poor-quality sleep and sleep deprivation [9,40,41]. In particular, SRMDs increase the risk of VD higher than that of AD because SRMDs are known to be strongly associated with metabolic disorders such as hypertension and diabetes, which can increase the risk of cardiovascular disease and cause VD [42,43]. The mechanism by which RLS and rapid eye movement sleep behavior disorder (RBD) affect cognitive decline is not clearly known. It can be indirectly understood through biochemical relationships among RLS, RBD and cognitive decline in patients with PD. Dysfunction in the dopaminergic system of those with RLS can cause motor abnormalities [44,45]. It is associated with cognitive impairment in PD patients [9]. In addition, RBD, which is an SRMD, is a risk factor for dementia [46,47]. Cholinergic deficits due to degeneration of the ascending pathway are associated with an increased risk of dementia in PD patients [47,48].

Table 1 summarizes the relationship between sleep disturbances and dementia.

INTERVENTION

It has been reported that approximately 15% of cases of cognitive impairment or AD can be prevented by effective interventions that reduce sleep disorders [11]. In addition, identifying and treating sleep disturbances in dementia patients has been suggested as a modifiable behavior that can reduce the risk of cognitive decline and dementia [5]. However, there is insufficient research on effects of interventions, such as pharmacological treatment, sleep hygiene management, and behavioral therapy, in decreasing the risk of dementia in patients with sleep disturbance [5].

CONCLUSIONS

Previous studies have shown that sleep disturbances can increase the risk of dementia, particularly AD and VD. Therefore, identifying sleep disturbances associated with dementia may help identify people at risk for developing dementia and facilitate preventive strategies. However, based on published studies up to date, although some associations between sleep disturbance and dementia have been confirmed, studies on clear causal relationships and interventions are lacking, confirming the need for additional research.

NOTES

Conflicts of Interest

The authors have no potential conflicts of interest to disclose.

Availability of Data and Material

Data sharing does not apply to this article, as no datasets were generated or analyzed during the study.

Author Contributions

Conceptualization: Eunji Lim, Dongyun Lee. Methodology: Bong-Jo Kim, Boseok Cha, So-Jin Lee. Formal analysis: Jae-Won Choi. Investigation: Nuree Kang. Writing—original draft: Eunji Lim, Dongyun Lee. Writing—review & editing: all authors.

Funding Statement

None

Acknowledgments

None

Table 1.

The relationship between sleep disturbances and dementia

Sleep disturbance	Risk of dementia (times)	Types of dementia	Mechanism
Short sleep duration	1.46	AD, VD	Aß clearance attenuation, IL-6, CRP elevation
Long sleep duration	1.74–2.2	AD, VD	IL-6, CRP elevation
Sleep-disordered breathing	1.58–1.85	AD, VD, PD, HD	WMC, Aβ formation and hippocampal atrophy
Sleep-related movement disorder	1.46–4	AD, VD, PD	Increased risk of CVD, dysfunction in dopaminergic system, cholinergic deficit

AD, Alzheimer’s disease; VD, vascular dementia; PD, Parkinson’s disease; HD, Huntington’s disease; Aβ, amyloid beta; IL-6, interleukin-6; CRP, C-reactive protein; WMC, white matter change; CVD, cardiovascular disease

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