Excessive Sleepiness and Longer Nighttime in Bed Increase the Risk of Cognitive Decline in Frail Elderly Subjects: The MAPT-Sleep Study

Audrey Gabelle, Laure-Anne Gutierrez, Isabelle Jaussent, Sophie Navucet, Caroline Grasselli, Karim Bennys, Cécilia Marelli, Renaud David, Sandrine Andrieu, Claudine Berr, Bruno Vellas, Yves Dauvilliers, Audrey Gabelle, Laure-Anne Gutierrez, Isabelle Jaussent, Sophie Navucet, Caroline Grasselli, Karim Bennys, Cécilia Marelli, Renaud David, Sandrine Andrieu, Claudine Berr, Bruno Vellas, Yves Dauvilliers

Abstract

Objective: To identify self-reported sleep-wake disturbances that increase the risk of cognitive decline over 1-year follow-up in frail participants. Background: Risk factors for cognitive impairment need to be better identified especially at earliest stages of the pathogenesis. Sleep-wake disturbances may be critical factors to consider and were thus being assessed in this at-risk population for cognitive decline. Methods: Frail elderly participants aged ≥70 years were selected from a subsample of the Multi-domain Alzheimer Preventive Trial (MAPT) for a sleep assessment (MAPT-sleep study) at 18-month follow-up (M18). Sleep-wake disturbances were evaluated using a clinical interview (duration of daytime and nighttime sleep, time in bed, number of naps, and presence of clinically-defined sleep disorders) and numerous validated questionnaires [Epworth Sleepiness Scale for excessive daytime sleepiness (EDS), Insomnia Severity Scale and Berlin Questionnaire]. Cognitive decline was defined as a difference between the MMSE and cognitive composite scores at M24 and M36 that was ranked in the lowest decile. Multivariate logistic regression models adjusted for several potential confounding factors were performed. Results: Among the 479 frail participants, 63 developed MMSE-cognitive decline and 50 cognitive composite score decrease between M24 and M36. Subjects with EDS had an increased risk of MMSE decline (OR = 2.46; 95% CI [1.28; 4.71], p = 0.007). A longer time spent in bed during night was associated with cognitive composite score decline (OR = 1.32 [1.03; 1.71], p = 0.03). These associations persisted when controlling for potential confounders. Patients with MMSE score decline and EDS had more naps, clinically-defined REM-sleep Behavior Disorder, fatigue and insomnia symptoms, while patients with cognitive composite score decline with longer time in bed had increased 24-h total sleep time duration but with higher wake time after onset. Conclusions: The risk of cognitive decline is higher in frailty subjects with EDS and longer nighttime in bed. Early detection of sleep-wake disturbances might help identifying frail subjects at risk of cognitive decline to further propose sleep health strategies to prevent cognitive impairment. http://www.clinicaltrials.gov NCT00672685; Date of registration May, 2nd 2008.

Keywords: Alzheimer disease; amyloid; cognitive decline; excessive daytime sleepiness; frailty and cognitive impairment; sleep.

Figures

Figure 1
Figure 1
Study flow chart.

References

    1. Benito-Leon J., Bermejo-Pareja F., Vega S., Louis E. D. (2009). Total daily sleep duration and the risk of dementia: a prospective population-based study. Eur. J. Neurol. 16, 990–997. 10.1111/j.1468-1331.2009.02618.x
    1. Benito-Leon J., Louis E. D., Bermejo-Pareja F. (2013). Cognitive decline in short and long sleepers: a prospective population-based study (NEDICES). J. Psychiatr. Res. 47, 1998–2003. 10.1016/j.jpsychires.2013.09.007
    1. Blachier M., Dauvilliers Y., Jaussent I., Helmer C., Ritchie K., Jouven X., et al. . (2012). Excessive daytime sleepiness and vascular events: the Three City Study. Ann. Neurol. 71, 661–667. 10.1002/ana.22656
    1. Branger P., Arenaza-Urquijo E. M., Tomadesso C., Mezenge F., Andre C., de Flores R., et al. . (2016). Relationships between sleep quality and brain volume, metabolism, and amyloid deposition in late adulthood. Neurobiol. Aging 41, 107–114. 10.1016/j.neurobiolaging.2016.02.009
    1. Cedernaes J., Osorio R. S., Varga A. W., Kam K., Schiöth H. B., Benedict C. (2017). Candidate mechanisms underlying the association between sleep-wake disruptions and Alzheimer's disease. Sleep Med. Rev. 31, 102–111. 10.1016/j.smrv.2016.02.002
    1. Dauvilliers Y. A., Lehmann S., Jaussent I., Gabelle A. (2014). Hypocretin and brain beta-amyloid peptide interactions in cognitive disorders and narcolepsy. Front. Aging Neurosci. 6:119. 10.3389/fnagi.2014.00119
    1. Devore E. E., Grodstein F., Duffy J. F., Stampfer M. J., Czeisler C. A., Schernhammer E. S. (2014). Sleep duration in midlife and later life in relation to cognition. J. Am. Geriatr. Soc. 62, 1073–1081. 10.1111/jgs.12790
    1. Donohue M. C., Sperling R. A., Salmon D. P., Rentz D. M., Raman R., Thomas R. G., et al. . (2014). The preclinical Alzheimer cognitive composite: measuring amyloid-related decline. JAMA Neurol. 71, 961–970. 10.1001/jamaneurol.2014.803
    1. Drogos L. L., Gill S. J., Tyndall A. V., Raneri J. K., Parboosingh J. S., Naef A., et al. . (2016). Evidence of association between sleep quality and APOE epsilon4 in healthy older adults: a pilot study. Neurology 87, 1836–1842. 10.1212/WNL.0000000000003255
    1. Emamian F., Khazaie H., Tahmasian M., Leschziner G. D., Morrell M. J., Hsiung G. Y., et al. . (2016). The association between obstructive sleep apnea and Alzheimer's disease: a meta-analysis perspective. Front. Aging Neurosci. 8:78. 10.3389/fnagi.2016.00078
    1. Fernandez-Mendoza J., Vgontzas A. N., Kritikou I., Calhoun S. L., Liao D., Bixler E. O. (2015). Natural history of excessive daytime sleepiness: role of obesity, weight loss, depression, and sleep propensity. Sleep 38, 351–360. 10.5665/sleep.4488
    1. Foley D., Monjan A., Masaki K., Ross W., Havlik R., White L., et al. . (2001). Daytime sleepiness is associated with 3-year incident dementia and cognitive decline in older Japanese-American men. J. Am. Geriatr. Soc. 49, 1628–1632. 10.1111/j.1532-5415.2001.49271.x
    1. Jaussent I., Bouyer J., Ancelin M. L., Akbaraly T., Peres K., Ritchie K., et al. . (2011). Insomnia and daytime sleepiness are risk factors for depressive symptoms in the elderly. Sleep 34, 1103–1110. 10.5665/SLEEP.1170
    1. Jaussent I., Bouyer J., Ancelin M. L., Berr C., Foubert-Samier A., Ritchie K., et al. . (2012). Excessive sleepiness is predictive of cognitive decline in the elderly. Sleep 35, 1201–1207. 10.5665/sleep.2070
    1. Jaussent I., Empana J. P., Ancelin M. L., Besset A., Helmer C., Tzourio C., et al. . (2013). Insomnia, daytime sleepiness and cardio-cerebrovascular diseases in the elderly: a 6-year prospective study. PLoS ONE 8:e56048. 10.1371/journal.pone.0056048
    1. Johar H., Kawan R., Emeny R. T., Ladwig K. H. (2016). Impaired sleep predicts cognitive decline in old people: findings from the prospective KORA age study. Sleep 39, 217–226. 10.5665/sleep.5352
    1. Keage H. A., Banks S., Yang K. L., Morgan K., Brayne C., Matthews F. E. (2012). What sleep characteristics predict cognitive decline in the elderly? Sleep Med. 13, 886–892. 10.1016/j.sleep.2012.02.003
    1. Loerbroks A., Debling D., Amelang M., Sturmer T. (2010). Nocturnal sleep duration and cognitive impairment in a population-based study of older adults. Int. J. Geriatr. Psychiatry 25, 100–109. 10.1002/gps.2305
    1. Lucey B. P., Holtzman D. M. (2015). How amyloid, sleep and memory connect. Nat. Neurosci. 18, 933–934. 10.1038/nn.4048
    1. Merlino G., Piani A., Gigli G. L., Cancelli I., Rinaldi A., Baroselli A., et al. . (2010). Daytime sleepiness is associated with dementia and cognitive decline in older Italian adults: a population-based study. Sleep Med. 11, 372–377. 10.1016/j.sleep.2009.07.018
    1. Niu J., Han H., Wang Y., Wang L., Gao X., Liao S. (2016). Sleep quality and cognitive decline in a community of older adults in Daqing City, China. Sleep Med. 17, 69–74. 10.1016/j.sleep.2015.07.033
    1. Ohayon M. M., Vecchierini M. F. (2002). Daytime sleepiness and cognitive impairment in the elderly population. Arch. Intern. Med. 162, 201–208. 10.1001/archinte.162.2.201
    1. Osorio R. S., Ayappa I., Mantua J., Gumb T., Varga A., Mooney A. M., et al. . (2014). Interaction between sleep-disordered breathing and apolipoprotein E genotype on cerebrospinal fluid biomarkers for Alzheimer's disease in cognitively normal elderly individuals. Neurobiol. Aging 35, 1318–1324. 10.1016/j.neurobiolaging.2013.12.030
    1. Ramos A. R., Gardener H., Rundek T., Elkind M. S., Boden-Albala B., Dong C., et al. . (2016). Sleep disturbances and cognitive decline in the Northern Manhattan Study. Neurology 87, 1511–1516. 10.1212/WNL.0000000000003168
    1. Roh J. H., Jiang H., Finn M. B., Stewart F. R., Mahan T. E., Cirrito J. R., et al. . (2014). Potential role of orexin and sleep modulation in the pathogenesis of Alzheimer's disease. J. Exp. Med. 211, 2487–2496. 10.1084/jem.20141788
    1. Slater G., Steier J. (2012). Excessive daytime sleepiness in sleep disorders. J. Thorac. Dis. 4, 608–616. 10.3978/j.issn.2072-1439.2012.10.07
    1. Slats D., Claassen J. A., Verbeek M. M., Overeem S. (2013). Reciprocal interactions between sleep, circadian rhythms and Alzheimer's disease: focus on the role of hypocretin and melatonin. Ageing Res. Rev. 12, 188–200. 10.1016/j.arr.2012.04.003
    1. Spira A. P., Gamaldo A. A., An Y., Wu M. N., Simonsick E. M., Bilgel M., et al. . (2013). Self-reported sleep and beta-amyloid deposition in community-dwelling older adults. JAMA Neurol. 70, 1537–1543. 10.1001/jamaneurol.2013.4258
    1. Sprecher K. E., Bendlin B. B., Racine A. M., Okonkwo O. C., Christian B. T., Koscik R. L., et al. . (2015). Amyloid burden is associated with self-reported sleep in nondemented late middle-aged adults. Neurobiol. Aging 36, 2568–2576. 10.1016/j.neurobiolaging.2015.05.004
    1. Sterniczuk R., Theou O., Rusak B., Rockwood K. (2013). Sleep disturbance is associated with incident dementia and mortality. Curr. Alzheimer Res. 10, 767–775. 10.2174/15672050113109990134
    1. Tworoger S. S., Lee S., Schernhammer E. S., Grodstein F. (2006). The association of self-reported sleep duration, difficulty sleeping, and snoring with cognitive function in older women. Alzheimer Dis. Assoc. Disord. 20, 41–48. 10.1097/01.wad.0000201850.52707.80
    1. Varga A. W., Wohlleber M. E., Gimenez S., Romero S., Alonso J. F., Ducca E. L., et al. . (2016). Reduced slow-wave sleep is associated with high cerebrospinal fluid abeta42 levels in cognitively normal elderly. Sleep 39, 2041–2048. 10.5665/sleep.6240
    1. Vellas B., Carrie I., Gillette-Guyonnet S., Touchon J., Dantoine T., Dartigues J. F., et al. . (2014). Mapt study: a multidomain approach for preventing Alzheimer's disease: design and baseline data. J. Prev. Alzheimers Dis. 1, 13–22.
    1. Virta J. J., Heikkila K., Perola M., Koskenvuo M., Raiha I., Rinne J. O., et al. . (2013). Midlife sleep characteristics associated with late life cognitive function. Sleep 36, 1533–1541, 1541A. 10.5665/sleep.3052
    1. Waller K. L., Mortensen E. L., Avlund K., Osler M., Fagerlund B., Lauritzen M., et al. . (2016). Subjective sleep quality and daytime sleepiness in late midlife and their association with age-related changes in cognition. Sleep Med. 17, 165–173. 10.1016/j.sleep.2015.01.004
    1. Xie L., Kang H., Xu Q., Chen M. J., Liao Y., Thiyagarajan M., et al. . (2013). Sleep drives metabolite clearance from the adult brain. Science 342, 373–377. 10.1126/science.1241224
    1. Yaffe K., Blackwell T., Barnes D. E., Ancoli-Israel S., Stone K. L. (2007). Preclinical cognitive decline and subsequent sleep disturbance in older women. Neurology 69, 237–242. 10.1212/01.wnl.0000265814.69163.da
    1. Yaffe K., Falvey C. M., Hoang T. (2014). Connections between sleep and cognition in older adults. Lancet Neurol. 13, 1017–1028. 10.1016/S1474-4422(14)70172-3

Source: PubMed

Patrocinadores e Colaboradores

Condições médicas

Intervenções de drogas

3
Se inscrever