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

Article information

Chronobiol Med. 2025;7(1):18-21

Publication date (electronic) : 2025 March 28

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

Eunji Lim ¹^,²

, Bong-Jo Kim ²^,³

, Boseok Cha ²^,³

, So-Jin Lee ²^,³

, Jae-Won Choi ²^,³

, Nuree Kang ³

, 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 2024 November 2; Revised 2025 February 24; Accepted 2025 February 24.

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.

Table 1.

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

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

Acknowledgements

None

References

1. GBD 2019 Dementia Forecasting Collaborators. Estimation of the global prevalence of dementia in 2019 and forecasted prevalence in 2050: an analysis for the Global Burden of Disease Study 2019. Lancet Public Health 2022;7:e105–e125.

2. GBD 2013 Mortality and Causes of Death Collaborators. Global, regional, and national age-sex specific all-cause and cause-specific mortality for 240 causes of death, 1990-2013: a systematic analysis for the Global Burden of Disease Study 2013. Lancet 2015;385:117–171.

3. Arvanitakis Z, Shah RC, Bennett DA. Diagnosis and management of dementia: review. JAMA 2019;322:1589–1599.

4. Livingston G, Huntley J, Sommerlad A, Ames D, Ballard C, Banerjee S, et al. Dementia prevention, intervention, and care: 2020 report of the Lancet Commission. Lancet 2020;396:413–446.

5. Wennberg AMV, Wu MN, Rosenberg PB, Spira AP. Sleep disturbance, cognitive decline, and dementia: a review. Semin Neurol 2017;37:395–406.

6. Aini N, Chu H, Banda KJ, Chen R, Lee TY, Pien LC, et al. Prevalence of sleep-related breathing disorders and associated risk factors among people with dementia: a meta-analysis. Sleep Med 2023;103:51–61.

7. Shi L, Chen SJ, Ma MY, Bao YP, Han Y, Wang YM, et al. Sleep disturbances increase the risk of dementia: a systematic review and meta-analysis. Sleep Med Rev 2018;40:4–16.

8. Lee JE, Yang SW, Ju YJ, Ki SK, Chun KH. Sleep-disordered breathing and Alzheimer’s disease: a nationwide cohort study. Psychiatry Res 2019;273:624–630.

9. Lin CC, Chou CH, Fan YM, Yin JH, Chung CH, Chien WC, et al. Increased risk of dementia among sleep-related movement disorders: a population-based longitudinal study in Taiwan. Medicine (Baltimore) 2015;94e2331.

10. Guarnieri B, Adorni F, Musicco M, Appollonio I, Bonanni E, Caffarra P, et al. Prevalence of sleep disturbances in mild cognitive impairment and dementing disorders: a multicenter Italian clinical cross-sectional study on 431 patients. Dement Geriatr Cogn Disord 2012;33:50–58.

11. Bubu OM, Brannick M, Mortimer J, Umasabor-Bubu O, Sebastião YV, Wen Y, et al. Sleep, cognitive impairment, and Alzheimer’s disease: a systematic review and meta-analysis. Sleep 2017;40:zsw032.

12. Xu W, Tan CC, Zou JJ, Cao XP, Tan L. Sleep problems and risk of all-cause cognitive decline or dementia: an updated systematic review and meta-analysis. J Neurol Neurosurg Psychiatry 2020;91:236–244.

13. Wong R, Lovier MA. Sleep disturbances and dementia risk in older adults: findings from 10 years of national U.S. prospective data. Am J Prev Med 2023;64:781–787.

14. Liang Y, Qu LB, Liu H. Non-linear associations between sleep duration and the risks of mild cognitive impairment/dementia and cognitive decline: a dose-response meta-analysis of observational studies. Aging Clin Exp Res 2019;31:309–320.

15. Lo JC, Groeger JA, Cheng GH, Dijk DJ, Chee MW. Self-reported sleep duration and cognitive performance in older adults: a systematic review and meta-analysis. Sleep Med 2016;17:87–98.

16. Howard C, Mukadam N, Hui EK, Livingston G. The effects of sleep duration on the risk of dementia incidence in short and long follow-up studies: a systematic review and meta-analysis. Sleep Med 2024;124:522–530.

17. Yaffe K, Laffan AM, Harrison SL, Redline S, Spira AP, Ensrud KE, et al. Sleep-disordered breathing, hypoxia, and risk of mild cognitive impairment and dementia in older women. JAMA 2011;306:613–619.

18. Kim KY, Kim EH, Lee M, Ha J, Jung I, Kim E. Restless leg syndrome and risk of all-cause dementia: a nationwide retrospective cohort study. Alzheimers Res Ther 2023;15:46.

19. Irwin MR, Vitiello MV. Implications of sleep disturbance and inflammation for Alzheimer’s disease dementia. Lancet Neurol 2019;18:296–306.

20. Irwin MR, Olmstead R, Carroll JE. Sleep disturbance, sleep duration, and inflammation: a systematic review and meta-analysis of cohort studies and experimental sleep deprivation. Biol Psychiatry 2016;80:40–52.

21. Jessen NA, Munk AS, Lundgaard I, Nedergaard M. The glymphatic system: a beginner’s guide. Neurochem Res 2015;40:2583–2599.

22. Musiek ES, Xiong DD, Holtzman DM. Sleep, circadian rhythms, and the pathogenesis of Alzheimer disease. Exp Mol Med 2015;47e148.

23. Sindi S, Kåreholt I, Johansson L, Skoog J, Sjöberg L, Wang HX, et al. Sleep disturbances and dementia risk: a multicenter study. Alzheimers Dement 2018;14:1235–1242.

24. Lo JC, Loh KK, Zheng H, Sim SK, Chee MW. Sleep duration and age-related changes in brain structure and cognitive performance. Sleep 2014;37:821.

25. Ooms S, Overeem S, Besse K, Rikkert MO, Verbeek M, Claassen JA. Effect of 1 night of total sleep deprivation on cerebrospinal fluid β-amyloid 42 in healthy middle-aged men: a randomized clinical trial. JAMA Neurol 2014;71:971–977.

26. Kang JE, Lim MM, Bateman RJ, Lee JJ, Smyth LP, Cirrito JR, et al. Amyloid-β dynamics are regulated by orexin and the sleep-wake cycle. Science 2009;326:1005–1007.

27. Mullington JM, Simpson NS, Meier-Ewert HK, Haack M. Sleep loss and inflammation. Best Pract Res Clin Endocrinol Metab 2010;24:775–784.

28. van Leeuwen WM, Lehto M, Karisola P, Lindholm H, Luukkonen R, Sallinen M, et al. Sleep restriction increases the risk of developing cardiovascular diseases by augmenting proinflammatory responses through IL-17 and CRP. PLoS One 2009;4e4589.

29. Prather AA, Vogelzangs N, Penninx BW. Sleep duration, insomnia, and markers of systemic inflammation: results from the Netherlands study of depression and anxiety (NESDA). J Psychiatr Res 2015;60:95–102.

30. Singh T, Newman AB. Inflammatory markers in population studies of aging. Ageing Res Rev 2011;10:319–329.

31. Cappuccio FP, Cooper D, D’Elia L, Strazzullo P, Miller MA. Sleep duration predicts cardiovascular outcomes: a systematic review and meta-analysis of prospective studies. Eur Heart J 2011;32:1484–1492.

32. Knutson KL. Sleep duration and cardiometabolic risk: a review of the epidemiologic evidence. Best Pract Res Clin Endocrinol Metab 2010;24:731–743.

33. Fotuhi M, Do D, Jack C. Modifiable factors that alter the size of the hippocampus with ageing. Nat Rev Neurol 2012;8:189–202.

34. Kim H, Yun CH, Thomas RJ, Lee SH, Seo HS, Cho ER, et al. Obstructive sleep apnea as a risk factor for cerebral white matter change in a middle-aged and older general population. Sleep 2013;36:709–715.

35. Cross NE, Memarian N, Duffy SL, Paquola C, LaMonica H, D’Rozario A, et al. Structural brain correlates of obstructive sleep apnoea in older adults at risk for dementia. Eur Respir J 2018;52:1800740.

36. Li L, Zhang X, Yang D, Luo G, Chen S, Le W. Hypoxia increases Aβ generation by altering β- and γ-cleavage of APP. Neurobiol Aging 2009;30:1091–1098.

37. Nair D, Dayyat EA, Zhang SX, Wang Y, Gozal D. Intermittent hypoxia-induced cognitive deficits are mediated by NADPH oxidase activity in a murine model of sleep apnea. PLoS One 2011;6e19847.

38. Yang J, Pan P, Song W, Huang R, Li J, Chen K, et al. Voxelwise meta-analysis of gray matter anomalies in Alzheimer’s disease and mild cognitive impairment using anatomic likelihood estimation. J Neurol Sci 2012;316:21–29.

39. Pacheco J, Goh JO, Kraut MA, Ferrucci L, Resnick SM. Greater cortical thinning in normal older adults predicts later cognitive impairment. Neurobiol Aging 2015;36:903–908.

40. Jung KY. Cognition in restless legs syndrome. J Sleep Med 2015;12:1–6.

41. Colzato LS, Zhang W, Brandt MD, Stock AK, Beste C. Cognitive profile in restless legs syndrome: a signal-to-noise ratio account. Curr Res Neurobiol 2021;2:100021.

42. Comair M, Awad S, Ghosh P. Sleep related movement disorders in the elderly: a review of recent literature. Front Sleep 2024;3:1356644.

43. Van Den Eeden SK, Albers KB, Davidson JE, Kushida CA, Leimpeter AD, Nelson LM, et al. Risk of cardiovascular disease associated with a restless legs syndrome diagnosis in a retrospective cohort study from Kaiser Permanente Northern California. Sleep 2015;38:1009–1015.

44. Manconi M, Garcia-Borreguero D, Schormair B, Videnovic A, Berger K, Ferri R, et al. Restless legs syndrome. Nat Rev Dis Primers 2021;7:80.

45. Hare D, Ayton S, Bush A, Lei P. A delicate balance: iron metabolism and diseases of the brain. Front Aging Neurosci 2013;5:34.

46. Postuma RB, Bertrand JA, Montplaisir J, Desjardins C, Vendette M, Rios Romenets S, et al. Rapid eye movement sleep behavior disorder and risk of dementia in Parkinson’s disease: a prospective study. Mov Disord 2012;27:720–726.

47. Marion MH, Qurashi M, Marshall G, Foster O. Is REM sleep behaviour disorder (RBD) a risk factor of dementia in idiopathic Parkinson’s disease? J Neurol 2008;255:192–196.

48. Emre M. Dementia in Parkinson's disease: cause and treatment. Curr Opin Neurol 2004;17:399–404.

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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