March/April 2019

Sleep: Impacts on Older Adult Health
By Jamie Santa Cruz
Today’s Geriatric Medicine
Vol. 12 No. 2 P. 12

A good night’s rest is key to wellness.

Sleep complaints are common among older adults; more than one-half report experiencing some kind of sleep difficulty, such as falling asleep, staying asleep, or not feeling rested most or all of the time.1 Up to 70% report at least one symptom of insomnia, such as difficulty falling asleep, difficulty staying asleep, and waking early in the morning.2 Poor sleep, in turn, is associated significantly with various comorbidities among older adults, including cognitive decline, diabetes, falls, and mood disorders. Increasing research suggests that sleep may play a causal role in each of these areas and that sleep may also be an important target for treating and preventing many such chronic conditions.

How Sleep Changes With Age
Age brings multiple changes in the structure of sleep. Older adults are prone to earlier bedtimes and rise times, typically take longer to fall asleep, have shorter sleep duration, experience more sleep fragmentation (eg, more awakenings), and are more likely to be awoken by external stimuli.3

Older adults also experience different kinds of sleep than their younger counterparts. For example, they typically experience less slow wave sleep, spend more time in lighter non–rapid eye movement (NREM) stages of sleep, and have shorter and fewer NREM-REM sleep cycles.3 Possibly because of these changes in nighttime sleep, 1 in 4 older adults also experiences sleepiness during the day sufficient to impair normal daily activities, and older adults unsurprisingly are more prone to napping during the day.4

Cognitive Function
Research in younger adults consistently links poor sleep with broad losses in cognitive functioning.5 Evidence regarding the effects of sleep on cognitive function in older adults is somewhat mixed, however.

Some research suggests, counterintuitively, that sleep is not significantly associated with cognitive function in older adults. A 2015 review found little evidence of an association between either short sleep or sleep fragmentation and cognitive measures in adults older than 60 years.6 The same review noted that in several cross-sectional studies, increased nighttime awakenings are correlated with improved cognitive performance among older adults.7,8 A separate review of experimental studies on sleep deprivation found that although sleep deprivation results in poorer cognitive performance in younger adults, the effect is less pronounced or nonexistent among older adults.5

By contrast, a 2016 meta-analysis and review found that there’s a significant association between sleep and cognition in older adults. Specifically, both short and long sleep duration were associated with poorer multiple-domain performance, executive function, verbal memory, and working memory performance.9 Furthermore, while much of the research on sleep and cognition in older adults relies on subjective reports of sleep, several large studies relying on objective measurements showed an association between poor sleep and cognitive function in aging populations.10-13

All research on sleep and cognition discussed so far has been cross-sectional, comparing sleep and cognition when both variables were measured at a single point in time in older age. But there’s another question to consider regarding sleep and cognition—namely, do sleep patterns earlier in life influence cognition in older age? An array of longitudinal studies suggests the answer is yes: Poor sleep in middle age predicts cognitive decline years into the future.

In one study of adults aged 45–69 years, participants’ sleep duration was assessed on two different occasions five years apart. On the latter occasion, their cognitive function was also measured via six different cognition tests. Those who reported an adverse change in sleep length between the first assessment and the second assessment (that is, a decrease from six, seven, or eight hours of sleep or an increase from seven or eight hours of sleep) had worse performance on most of the cognition tests.14 In another study of middle-aged adults, self-reported sleep length and quality predicted cognitive decline as measured in a telephone interview 22 years later.15 Thus, there’s reason to believe that sleep disturbances in middle-age promote cognitive impairments years later.6

Alzheimer’s Disease and Other Dementias
Sleep disorders are common in individuals with Alzheimer’s disease (AD) and were once assumed to be a consequence of the disease. However, several studies have linked disordered sleep and extreme sleep duration to greater likelihood of developing AD over time,16-19 suggesting a bidirectional relationship between sleep disturbance and AD pathophysiology.20

The accumulation of amyloid-β (Aβ) and its subsequent formation into amyloid plaques is a hallmark of AD. According to Bryce Mander, PhD, an assistant professor of psychiatry and human behavior in the School of Medicine at the University of California, Irvine, classic rodent models of AD have shown that amyloid pathology in interstitial fluid in the brain follows a circadian rhythm. “It rises when they’re awake, and it goes down when they’re asleep,” Mander says. “If you sleep-deprive the rodents, you increase the plaques in the brain. This was one of the first pieces of evidence that actively disrupting or reducing sleep was actually increasing amyloid plaque production.”

In humans, multiple cross-sectional studies have now linked poor sleep with greater Aβ burden.21,22 Although cross-sectional research cannot speak to causality, several experimental studies do suggest the link is causal. One study of middle-aged men found that after a night of normal sleep, Aβ burden in cerebrospinal fluid decreased by 6%. However, after a night of sleep deprivation, no such reduction occurred.23 Similarly, a second small study of healthy controls found that just one night of sleep deprivation produced a significant increase in Aβ burden relative to baseline measurements after a night of normal sleep.24

Although it’s clear that poor sleep increases risk of AD, the precise mechanisms are less clear. Two have been proposed, according to Mander. The first is that there’s a fundamental difference between how neurons fire in wakefulness vs sleep that increases amyloid production. “Neurons are much more metabolically active, use much more oxygen, and so build up more oxidative stress in wakefulness relative to non-REM sleep—and those are all mechanisms that are linked to Aβ production,” Mander says. The other proposed mechanism relates to the glymphatic system, which is the mechanism the brain uses to deal with waste. “Essentially, the glymphatic system power-washes the brain, flushing cerebrospinal fluid from the brain to wash away all the external toxins and proteins that may damage neurons,” Mander says. This process occurs preferentially during NREM sleep; thus, the theory is that if NREM sleep is disrupted, it disrupts the brain’s ability to flush toxins. Either way, however, what appears clear is that poor sleep likely plays a causal role in AD and that addressing sleep may in turn may be key to preventing or delaying AD.

Cardiometabolic Health
According to Kristen Knutson, PhD, an associate professor of neurology and preventive medicine in the Feinberg School of Medicine at Northwestern University, significant research also suggests a link between sleep and cardiometabolic health among older adults. The research falls into two categories, Knutson says—namely, observational studies, which show associations but do not demonstrate causality, and experimental studies, which are short term but better establish causal links.

Experimental research in the general population has shown that restricting and disrupting sleep both produce impairments in markers of cardiometabolic health. Specifically, acute short-term sleep restriction raises blood pressure,25,26 induces insulin resistance,27-30 impairs glucose tolerance,31 prompts inflammation,32,33 and leads to weight gain.34

Although research on lipids is not entirely inconsistent,35 some studies suggest that sleep affects lipid levels. One study involving both an experimental and observational component found that restricting sleep increased expression of genes in inflammatory pathways and decreased expression of genes relating to cholesterol transport. Short sleep was also associated with lower HDL, an important risk factor for cardiovascular disease. Such research suggests that sleep deprivation may influence cardiovascular health by modifying inflammatory and cholesterol pathways all the way down at the level of gene expression.36

These experimental studies were short term and were conducted in the general adult population, not among older adults. However, observational studies among older adults suggest long-term associations.

For instance, multiple studies have found that both short and long sleep duration are associated with poorer glycemic control and with elevated risk of prediabetes and incident type 2 diabetes mellitus.37-41 Similarly, multiple studies have found a significant association between insufficient sleep duration and obesity.42,43 However, the research on obesity has not always been consistent, and a 2016 review concluded that the relationship between sleep duration and obesity, if one exists, appears stronger in younger adults than in older adults.44 A factor that may explain some of the inconsistency is that many studies on sleep and obesity have relied on self-report. Older adults experience high rates of sleep disorders, which may cause a misperception of time spent sleeping and misreporting on self-reports. Indeed, at least one cross-sectional study found no relationship between sleep and obesity in older adults when relying on self-reports, but did find a significant association when using actigraphy to measure sleep objectively. Specifically, short sleep duration, long sleep duration, and sleep fragmentation were all associated with increased obesity risk.45

In the general adult population, sleep duration has been linked to cardiovascular disease46-49 and to hypertension, an important risk factor for cardiovascular disease.50-52 However, the link between hypertension and sleep duration appears to weaken with age. A number of studies have found that the association is either reduced or nonexistent in older adults—possibly because other risk factors for hypertension may obscure any association.51,53-56 With cardiovascular disease, by contrast, there’s some evidence that the association with sleep remains significant with age.57-59 A cohort study of 400,000 Taiwanese adults found that extreme sleep duration (both short and long) predicted substantially increased risk of death from coronary heart disease, and that the associations were stronger in older vs younger adults.60

As for mechanisms, the autonomic nervous system is one suspected player, according to Knutson. “What we think is happening is that impaired sleep or insufficient sleep is eliciting a stress response, and we know chronic stress elevation is associated with cardiometabolic risk.” The endocrine system is likely also involved, Knutson adds. Sleep deprivation and impairment could prompt changes in the regulation and production of, say, appetite hormones, leading in turn to increased food intake, obesity, and then cardiometabolic disorders. “The production of a lot of hormones seem to change in short-term experimental studies in response to sleep restriction and impairment,” Knutson says.

Fall Risk
Multiple studies have established a link between sleep duration (both long and short) and increased risk of falling in older adults.61-64 In a recent cross-sectional analysis of Korean adults older than age 65, sleeping five hours or less per night was significantly associated with risk of injury from falling; sleeping more than eight hours was also associated with higher risk, though to a lesser extent.65 Additional research has focused on sleep quality rather than merely on duration. In a prospective observational study of older men, sleep disturbances, including sleep fragmentation and nocturnal hypoxemia, were associated with a higher risk of falling in the subsequent year.66 Another cross-sectional study relying on self-reported sleep disturbances likewise found an association between number of nocturnal awakenings and fall risk.67

There remains debate about whether sleep problems themselves increase the risk of fall or whether fall risk is increased by the medications used to treat sleep difficulties. Most studies have not examined sleep issues independently from medication use. However, in one prospective study, self-reported short sleep duration of five hours or less per night at baseline was associated with increased odds of having two or more falls in the subsequent year, independent of benzodiazepine use.68

Mood and Suicide
Sleep problems are predictive of depression among older adults. In one cohort of older women with few or no symptoms of depression at baseline, both subjective sleep disturbance and objective sleep fragmentation were associated with greater odds of worsening depression five years later.69 In another longitudinal study, both short sleep duration and disturbed sleep (based on subjective reports) were predictive of increased depressive symptoms six years later.70

The relationship between sleep and depression appears to be bidirectional. A 2017 meta-analysis found that self-reported sleep disturbances increased the risk of the development, worsening, and reoccurrence of depression. But the reverse also held true: Participants with depression were more likely to experience both onset and worsening of sleep disturbances.71

Poor sleep is likewise associated with an elevated risk of suicide. In a 10-year case-control observational study, older adults with self-reported poor sleep quality were 1.4 times more likely to die by suicide than were participants who slept well. This association remained even after adjusting for depressive symptoms.72

According to Katie L. Stone, PhD, senior scientist at the California Pacific Medical Center Research Institute and an adjunct professor in the department of epidemiology and biostatistics at the University of California, San Francisco, the mechanisms by which sleep may affect mood may involve both direct and indirect pathways. While biological factors could be involved, the fact that sleep influences other aspects of health could also play a role. “Anecdotally, if you sleep poorly and it impacts other aspects of your quality of life, of your health in general, that could negatively impact mood. It could be just one aspect of an overall general lack of well-being,” Stone says. The bidirectional nature of mood disorders and sleep problems is also important to bear in mind, she adds. “If you’re sleeping poorly and it impacts mood, then that also interferes with your ability to sleep. It becomes a cyclical pattern of one contributing to the other.”

Implications for Clinicians
Much remains to be studied about the specific impacts of poor sleep on older adult health. However, according to Joseph Dzierzewski, PhD, an assistant professor of clinical psychology at Virginia Commonwealth University, the increasing evidence with respect to the associations and likely causal relationships between sleep and various aspects of health underscore the need for clinicians to take sleep seriously in older adult patients. “We recommend screening for insomnia and sleep apnea on routine visits with geriatricians,” he says. “Geriatricians are the gate keepers.”

The issue of treatment is still complex, unfortunately. “We do have very good, well-established, evidence-based treatments for disorders such as insomnia and sleep-disordered breathing,” Dzierzewski says. However, it’s not always clear what effect sleep treatments will have on other health conditions, such as cognitive impairment. Some experimental research has explored this question, but with disappointing results.73 “The vast majority of studies of sleep treatments have not shown the widespread improvements in cognition that we would like to have seen,” Dzierzewski says.

Similarly, the efficacy of sleep interventions for improving depression is not yet clear. “We don’t know the extent to which some of those changes that occur are reversible,” Stone says. In the general adult population, there is some early evidence that sleep interventions improve mood.74 But some research suggests that such interventions may not have as much impact among older adults. For example, in one study, a brief behavioral treatment for insomnia improved multiple insomnia symptoms (including sleep onset latency, wake after sleep onset, total sleep time, sleep efficiency, and sleep quality ratings) as measured by actigraphy. However, the treatment did not improve symptoms of depression over the reductions seen in controls.75

According to Dzierzewski, some of the lackluster results so far, at least with respect to cognition, may simply be due to the short duration of the studies. “If someone has been sleeping poorly for a decade, improvement of sleep over four to six weeks may not be enough time to show improvements in cognition,” he says. Both Dzierzewski and Stone agree that better studies are needed to show the potential influence of sleep interventions on comorbid conditions.

But regardless of whether sleep interventions improve cognition or influence depression, Dzierzewski believes sleep problems should be treated—preferably using cognitive behavioral therapy rather than medication. “We don’t have definitive answers about whether intervening on sleep could reduce the risk or thwart the progression of AD or other dementias,” Dzierzewski says. “However, you’re not going to harm someone by treating sleep problems, and improving their sleep would at a minimum improve quality of life.”

— Jamie Santa Cruz is a health and medical journalist based in Parker, Colorado.

References
1. Foley DJ, Monjan AA, Brown SL, Simonsick EM, Wallace RB, Blazer DG. Sleep complaints among elderly persons: an epidemiologic study of three communities. Sleep. 1995;18(6):425-432.

2. Jaussent I, Dauvilliers Y, Ancelin ML, et al. Insomnia symptoms in older adults: associated factors and gender differences. Am J Geriatr Psychiatry. 2011;19(1):88-97.

3. Mander BA, Winer JR, Walker MP. Sleep and human aging. Neuron. 2017;94(1):19-36.

4. Foley DJ, Vitiello MV, Bliwise DL, Ancoli-Israel S, Monjan AA, Walsh JK. Frequent napping is associated with excessive daytime sleepiness, depression, pain, and nocturia in older adults: findings from the National Sleep Foundation ‘2003 Sleep in America’ Poll. Am J Geriatr Psychiatry. 2007;15(4):344-350.

5. Alhola P, Polo-Kantola P. Sleep deprivation: impact on cognitive performance. Neuropsychiatr Dis Treat. 2007;3(5):553-567.

6. Scullin MK, Bliwise DL. Sleep, cognition, and normal aging: integrating a half century of multidisciplinary research. Perspect Psychol Sci. 2015;10(1):97-137.

7. McCrae CS, Vatthauer KE, Dzierzewski JM, Marsiske M. Habitual sleep, reasoning, and processing speed in older adults with sleep complaints. Cognit Ther Res. 2012;36(2):156-164.

8. Miller MA, Wright H, Ji C, Cappuccio FP. Cross-sectional study of sleep quantity and quality and amnestic and non-amnestic cognitive function in an ageing population: the English Longitudinal Study of Ageing (ELSA). PLoS One. 2014;9(6):e100991.

9. 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.

10. Blackwell T, Yaffe K, Ancoli-Israel S, et al. Poor sleep is associated with impaired cognitive function in older women: the study of osteoporotic fractures. J Gerontol A Biol Sci Med Sci. 2006;61(4):405-410.

11. Blackwell T, Yaffe K, Laffan A, et al. Associations of objectively and subjectively measured sleep quality with subsequent cognitive decline in older community-dwelling men: the MrOS sleep study. Sleep. 2014;37(4):655-663.

12. Lim AS, Yu L, Costa MD, et al. Increased fragmentation of rest-activity patterns is associated with a characteristic pattern of cognitive impairment in older individuals. Sleep. 2012;35(5):633-640.

13. Cavuoto MG, Ong B, Pike KE, Nicholas CL, Bei B, Kinsella GJ. Objective but not subjective sleep predicts memory in community-dwelling older adults. J Sleep Res. 2016;25(4):475-485.

14. Ferrie JE, Shipley MJ, Akbaraly TN, Marmot MG, Kivimäki M, Singh-Manoux A. Change in sleep duration and cognitive function: findings from the Whitehall II Study. Sleep. 2011;34(5):565-573.

15. Virta JJ, Heikkilä K, Perola M, et al. Midlife sleep characteristics associated with late life cognitive function. Sleep. 2013;36(10):1533-1541.

16. Osorio RS, Pirraglia E, Agüera-Ortiz LF, et al. Greater risk of Alzheimer’s disease in older adults with insomnia. J Am Geriatr Soc. 2011;59(3):559-562.

17. Yaffe K, Laffan AM, Harrison SL, et al. Sleep-disordered breathing, hypoxia, and risk of mild cognitive impairment and dementia in older women. JAMA. 2011;306(6):613-619.

18. Sharma RA, Varga AW, Bubu OM, et al. Obstructive sleep apnea severity affects amyloid burden in cognitively normal elderly: a longitudinal study. Am J Respir Crit Care Med. 2018;197(7):933-943.

19. Ohara T, Honda T, Hata J, et al. Association between daily sleep duration and risk of dementia and mortality in a Japanese community. J Am Geriatr Soc. 2018;66(10):1911-1918.

20. Brown BM, Rainey-Smith SR, Bucks RS, Weinborn M, Martins RN. Exploring the bi-directional relationship between sleep and beta-amyloid. Curr Opin Psychiatry. 2016;29(6):397-401.

21. Ju YE, McLeland JS, Toedebusch CD, et al. Sleep quality and preclinical Alzheimer disease. JAMA Neurol. 2013;70(5):587-593.

22. Spira AP, Gamaldo AA, An Y, et al. Self-reported sleep and β-amyloid deposition in community-dwelling older adults. JAMA Neurol. 2013;70(12):1537-1543.

23. 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(8):971-977.

24. Shokri-Kojori E, Wang G-J, Wiers CE, et al. β-Amyloid accumulation in the human brain after one night of sleep deprivation. Proc Natl Acad Sci U S A. 2018;115(17):4483-4488

25. Ogawa Y, Kanbayashi T, Saito Y, et al. Total sleep deprivation elevates blood pressure through arterial baroreflex resetting: a study with microneurographic technique. Sleep. 2003;26(8):986-989.

26. Covassin N, Bukartyk J, Sahakyan K, et al. Experimental sleep restriction increases nocturnal blood pressure and attenuates blood pressure dipping in healthy individuals. J Am Coll Cardiol. 2015;65(10 Suppl):61352-61353.

27. Spiegel K, Knutson K, Leproult R, Tasali E, Van Cauter E. Sleep loss: a novel risk factor for insulin resistance and type 2 diabetes. J Appl Physiol (1985). 2005;99(5):2008-2019.

28. Donga E, van Dijk M, van Dijk JG, et al. A single night of partial sleep deprivation induces insulin resistance in multiple metabolic pathways in healthy subjects. J Clin Endocrinol Metab. 2010;95(6):2963-2968.

29. Van Cauter E, Spiegel K, Tasali E, Leproult R. Metabolic consequences of sleep and sleep loss. Sleep Med. 2008;9(Suppl 1):S23-S28.

30. Buxton OM, Pavlova M, Reid EW, Wang W, Simonson DC, Adler GK. Sleep restriction for 1 week reduces insulin sensitivity in healthy men. Diabetes. 2010;59(9):2126-2133.

31. Spiegel K, Leproult R, Van Cauter E. Impact of sleep debt on metabolic and endocrine function. Lancet. 1999;354(9188):1435-1439.

32. Meier-Ewert HK, Ridker PM, Rifai N, et al. Effect of sleep loss on C-reactive protein, an inflammatory marker of cardiovascular risk. J Am Coll Cardiol. 2004;43(4):678-683.

33. van Leeuwen WM, Lehto M, Karisola P, et al. Sleep restriction increases the risk of developing cardiovascular diseases by augmenting proinflammatory responses through IL-17 and CRP. PLoS One. 2009;4(2):e4589.

34. Spaeth AM, Dinges DF, Goel N. Effects of experimental sleep restriction on weight gain, caloric intake, and meal timing in healthy adults. Sleep. 2013;36(7):981-990.

35. O’Keeffe M, Roberts AL, Kelleman M, Roychoudhury A, St-Onge MP. No effects of short-term sleep restriction, in a controlled feeding setting, on lipid profiles in normal-weight adults. J Sleep Res. 2013;22(6):717-720.

36. Aho V, Ollila HM, Kronholm E, et al. Prolonged sleep restriction induces changes in pathways involved in cholesterol metabolism and inflammatory responses. Sci Rep. 2016;6:24828.

37. Gottlieb DJ, Punjabi NM, Newman AB, et al. Association of sleep time with diabetes mellitus and impaired glucose tolerance. Arch Intern Med. 2005;165(8):863-867.

38. Gangwisch JE, Heymsfield SB, Boden-Albala B, et al. Sleep duration as a risk factor for diabetes incidence in a large U.S. sample. Sleep. 2007;30(12):1667-1673.

39. Xu Q, Song Y, Hollenbeck A, Blair A, Schatzkin A, Chen H. Day napping and short night sleeping are associated with higher risk of diabetes in older adults. Diabetes Care. 2009;33(1):78-83.

40. Leng Y, Cappuccio FP, Surtees PG, Luben R, Brayne C, Khaw KT. Daytime napping, sleep duration and increased 8-year risk of type 2 diabetes in a British population. Nutr Metab Cardiovasc Dis. 2016;26(11):996-1003.

41. Nakajima K, Suwa K, Toyama K. Age-dependent changes in the association between sleep duration and impaired glucose metabolism. World J Diabetes. 2017;8(8):397-406.

42. Buxton OM, Marcelli E. Short and long sleep are positively associated with obesity, diabetes, hypertension, and cardiovascular disease among adults in the United States. Soc Sci Med. 2010;71(5):1027-1036.

43. Patel SR, Blackwell T, Redline S, et al. The association between sleep duration and obesity in older adults. Int J Obes (Lond). 2008;32(12):1825-1834.

44. Theorell-Haglöw J, Lindberg E. Sleep duration and obesity in adults: what are the connections? Curr Obes Rep. 2016;5(3):333-343.

45. van den Berg JF, Knvistingh Neven A, Tulen JH, et al. Actigraphic sleep duration and fragmentation are related to obesity in the elderly: the Rotterdam Study. Int J Obes (Lond). 2008;32(7):1083-1090.

46. Chandola T, Ferrie JE, Perski A, Akbaraly T, Marmot MG. The effect of short sleep duration on coronary heart disease risk is greatest among those with sleep disturbance: a prospective study from the Whitehall II cohort. Sleep. 2010;33(6):739-744.

47. Ayas NT, White DP, Manson JE, et al. A prospective study of sleep duration and coronary heart disease in women. Arch Intern Med. 2003;163(2):205-209.

48. 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(12):1484-1492.

49. Hoevenaar-Blom MP, Spijkerman AM, Kromhout D, Verschuren WM. Sufficient sleep duration contributes to lower cardiovascular disease risk in addition to four traditional lifestyle factors: the MORGEN study. Eur J Prev Cardiol. 2014;21(11):1367-1375.

50. Buxton OM, Marcelli E. Short and long sleep are positively associated with obesity, diabetes, hypertension, and cardiovascular disease among adults in the United States. Soc Sci Med. 2010;71(5):1027-1036.

51. Kim J, Jo I. Age-dependent association between sleep duration and hypertension in the adult Korean population. Am J Hypertens. 2010;23(12):1286-1291.

52. Gottlieb DJ, Redline S, Nieto FJ, et al. Association of usual sleep duration with hypertension: the Sleep Heart Health Study. Sleep. 2006;29(8):1009-1014.

53. van den Berg JF, Tulen JH, Neven AK, et al. Sleep duration and hypertension are not associated in the elderly. Hypertension. 2007;50(3):585-589.

54. Lopez-Garcia E, Faubel R, Guallar-Castillon P, Leon-Muñoz L, Banegas JR, Rodriguez-Artalejo F. Self-reported sleep duration and hypertension in older Spanish adults. J Am Geriatr Soc. 2009;57(4):663-668.

55. Stranges S, Dorn JM, Cappuccio FP, et al. A population-based study of reduced sleep duration and hypertension: the strongest association may be in premenopausal women. J Hypertens. 2010;28(5):896-902.

56. Lima-Costa MF, Peixoto SV, Rocha FL. Usual sleep duration is not associated with hypertension in Brazilian elderly: the Bambui Health Aging Study (BHAS). Sleep Med. 2008;9:806-807.

57. da Silva AA, de Mello RG, Schaan CW, Fuchs FD, Redline S, Fuchs SC. Sleep duration and mortality in the elderly: a systematic review with meta-analysis. BMJ Open. 2016;6(2):e008119.

58. Rissling MB, Gray KE, Ulmer CS, et al. Sleep disturbance, diabetes, and cardiovascular disease in postmenopausal veteran women. Gerontologist. 2016;56(Suppl 1):S54-S66.

59. Chair SY, Wang Q, Cheng HY, et al. Relationship between sleep quality and cardiovascular disease risk in Chinese post-menopausal women. BMC Womens Health. 2017;17(1):79.

60. Strand LB, Tsai MK, Gunnell D, Janszky I, Wen CP, Chang SS. Self-reported sleep duration and coronary heart disease mortality: a large cohort study of 400,000 Taiwanese adults. Int J Cardiol. 2016;207:246-251.

61. Kuo HK, Yang CC, Yu YH, Tsai KT, Chen CY. Gender-specific association between self-reported sleep duration and falls in high-functioning older adults. J Gerontol A Biol Sci Med Sci. 2010;65(2):190-196.

62. Mesas AE, López-García E, Rodríguez-Artalejo F. Self-reported sleep duration and falls in older adults. J Sleep Res. 2011;20(1 Pt 1):21-27.

63. Kim SY, Kim SG, Sim S, Park B, Choi HG. Excessive sleep and lack of sleep are associated with slips and falls in the adult Korean population: a population-based cross-sectional study. Medicine (Baltimore). 2016;95(4):e2397.

64. Helbig AK, Döring A, Heier M, et al. Association between sleep disturbances and falls among the elderly: results from the German cooperative Health Research in the region of Augsburg-age study. Sleep Med. 2013;14(12):1356-1363.

65. Noh JW, Kim KB, Lee JH, Lee Y, Lee BH, Kwon YD. Association between sleep duration and injury from falling among older adults: a cross-sectional analysis of Korean community health survey data. Yonsei Med J. 2017;58(6):1222-1228.

66. Stone KL, Blackwell TL, Ancoli-Israel S, et al. Sleep disturbances and risk of falls in older community-dwelling men: the outcomes of sleep disorders in older men (MrOS sleep) study. J Am Geriatr Soc. 2014;62(2):299-305.

67. Latimer Hill E, Cumming RG, Lewis R, Carrington S, Le Couteur DG. Sleep disturbances and falls in older people. J Gerontol A Biol Sci Med Sci. 2007;62:62-66.

68. Stone KL, Ancoli-Israel S, Blackwell T, et al. Actigraphy-measured sleep characteristics and risk of falls in older women. Arch Intern Med. 2008;168(16):1768-1775.

69. Maglione JE, Ancoli-Israel S, Peters KW, et al. Subjective and objective sleep disturbance and longitudinal risk of depression in a cohort of older women. Sleep. 2014;37(7):1179-1187.

70. Jackowska M, Poole L. Sleep problems, short sleep and a combination of both increase the risk of depressive symptoms in older people: a 6-year follow-up investigation from the English Longitudinal Study of Ageing. Sleep Med. 2017;37:60-65.

71. Bao YP, Han Y, Ma J, et al. Cooccurrence and bidirectional prediction of sleep disturbances and depression in older adults: meta-analysis and systematic review. Neurosci Biobehav Rev. 2017;75:257-273.

72. Bernert RA, Turvey CL, Conwell Y, Joiner TE Jr. Association of poor subjective sleep quality with risk for death by suicide during a 10-year period: a longitudinal, population-based study of late life. JAMA Psychiatry. 2014;71(10):1129-1137.

73. Naismith SL, Pye J, Terpening Z, Lewis S, Bartlett D. “Sleep Well, Think Well” group program for mild cognitive impairment: a randomized controlled pilot study [published online September 24, 2018]. Behav Sleep Med. doi: 10.1080/15402002.2018.1518223.

74. Manber R, Edinger JD, Gress JL, San Pedro-Salcedo MG, Kuo TF, Kalista T. Cognitive behavioral therapy for insomnia enhances depression outcome in patients with comorbid major depressive disorder and insomnia. Sleep. 2008;31(4):489-495.

75. McCrae CS, Curtis AF, Williams JM, et al. Efficacy of brief behavioral treatment for insomnia in older adults: examination of sleep, mood, and cognitive outcomes. Sleep Med. 2018;51:153-166.