Naturalistic Measurement of Sleep in Older Adults with Amnestic Mild Cognitive Impairment: Anxiety Symptoms Do Not Explain Sleep Disturbance

Author(s): Marina G. Cavuoto* , Glynda J. Kinsella , Ben Ong , Kerryn E. Pike , Christian L. Nicholas .

Journal Name: Current Alzheimer Research

Volume 16 , Issue 3 , 2019

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Background: Sleep disturbance is prevalent in Alzheimer’s disease (AD). In amnestic mild cognitive impairment (aMCI), the preclinical stage of AD, deterioration in sleep quality has also been reported. Consensus is lacking, however, regarding what aspects of sleep are characteristically affected, whether the setting of the sleep recordings impacts these findings, and whether anxiety may account for the differences.

Objective: The current study aimed to address these knowledge gaps by obtaining comprehensive sleep measurement in aMCI within a naturalistic environment using in-home sleep recordings.

Methods: 17 healthy older adults and twelve participants with aMCI wore an actiwatch for two weeks to objectively record habitual sleeping patterns and completed two nights of in-home polysomnography.

Results: In aMCI, habitual sleep disturbances were evident on actigraphy including greater wake after sleep onset (p = .012, d = 0.99), fragmentation (p = .010, d = 1.03), and time in bed (p = .046, d = .76). Although not statistically significant, there was a large group effect on polysomnography with aMCI demonstrating less slow-wave-sleep than controls (p >.05, d = .0.83). Anxiety did not mediate the relationship between the group and sleep in this small study.

Conclusions: The results indicate that people with aMCI have poorer quality sleep than healthy controls, as indicated by greater sleep disruption and less slow-wave sleep, even in naturalistic settings. Additionally, anxiety symptoms do not mediate the relationship. Therefore, this research supports the view that sleep disturbance is likely to be indicative of neuropathological changes in aMCI rather than being attributed to psychological factors.

Keywords: Sleep, Alzheimer disease, mild cognitive impairment, cognitive dysfunction, sleep disturbances, polysomnography, neuropsychology, actigraphy.

Prinz PN, Vitaliano PP, Vitiello MV, Bokan J, Raskind M, Peskind E, et al. Sleep, EEG and mental function changes in senile dementia of the Alzheimer’s type. Neurobiol Aging 3(4): 361-70. (1982)
Vitiello MV, Prinz PN, Williams DE, Frommlet MS, Ries RK. Sleep disturbances in patients with mild-stage Alzheimer’s disease. J Gerontol 45(4): M131-8. (1990)
Liguori C, Romigi A, Nuccetelli M, Zannino S, Sancesario G, Martorana A, et al. Orexinergic system dysregulation, sleep impairment, and cognitive decline in Alzheimer disease. JAMA Neurol 71(12): 1498-505. (2014)
Ju YE, Lucey BP, Holtzman DM. Sleep and Alzheimer disease pathology--a bidirectional relationship. Nat Rev Neurol 10(2): 115-9. (2014)
Mander BA, Winer JR, Jagust WJ, Walker MP. Sleep: A novel mechanistic pathway, biomarker, and treatment target in the pathology of Alzheimer’s disease? Trends Neurosci 39(8): 552-66. (2016)
Liu RY, Zhou JN, van Heerikhuize J, Hofman MA, Swaab DF. Decreased melatonin levels in postmortem cerebrospinal fluid in relation to aging, Alzheimer’s disease, and apolipoprotein E-ε4/4 genotype. J Clin Endocrinol Metab 84(1): 323-7. (1999)
Musiek ES, Xiong DD, Holtzman DM. Sleep, circadian rhythms, and the pathogenesis of Alzheimer disease. Exp Mol Med 47: e148. (2015)
Stern AL, Naidoo N. Wake-active neurons across aging and neurodegeneration: A potential role for sleep disturbances in promoting disease. Springerplus 4(25): 25. (2015)
Kang JE, Lim MM, Bateman RJ, Lee JJ, Smyth LP, Cirrito JR, et al. Amyloid-beta dynamics are regulated by orexin and the sleep-wake cycle. Science 326(5955): 1005-7. (2009)
Qiu H, Zhong R, Liu H, Zhang F, Li S, Le W. Chronic sleep deprivation exacerbates learning-memory disability and Alzheimer’s disease-like pathologies in AbetaPP(swe)/PS1(DeltaE9) mice. J Alzheimers Dis 50(3): 669-85. (2016)
Rothman SM, Herdener N, Frankola KA, Mughal MR, Mattson MP. Chronic mild sleep restriction accentuates contextual memory impairments, and accumulations of cortical Abeta and pTau in a mouse model of Alzheimer’s disease. Brain Res 1529: 200-8. (2013)
Xie L, Kang H, Xu Q, Chen MJ, Liao Y, Thiyagarajan M, et al. Sleep drives metabolite clearance from the adult brain. Science 342(6156): 373-7. (2013)
Shokri-Kojori E, Wang GJ, Wiers CE, Demiral SB, Guo M, Kim SW, et al. beta-Amyloid accumulation in the human brain after one night of sleep deprivation. Proc Natl Acad Sci USA 115(17): 4483-8. (2018)
Busche MA, Kekus M, Adelsberger H, Noda T, Forstl H, Nelken I, et al. Rescue of long-range circuit dysfunction in Alzheimer’s disease models. Nat Neurosci 18(11): 1623-30. (2015)
Naismith SL, Mowszowski L. Sleep disturbance in mild cognitive impairment: a systematic review of recent findings. Curr Opin Psychiatry 31(2): 153-9. (2018)
Hayes TL, Riley T, Mattek N, Pavel M, Kaye JA. Sleep habits in mild cognitive impairment. Alzheimer Dis Assoc Disord 28(2): 145-50. (2014)
Hita-Yanez E, Atienza M, Cantero JL. Polysomnographic and subjective sleep markers of mild cognitive impairment. Sleep 36(9): 1327-34. (2013)
Hita-Yanez E, Atienza M, Gil-Neciga E, Cantero JL. Disturbed sleep patterns in elders with Mild Cognitive Impairment: the role of memory decline and ApoE 4 genotype. Curr Alzheimer Res 9(3): 290-7. (2012)
Liguori C, Nuccetelli M, Izzi F, Sancesario G, Romigi A, Martorana A, et al. Rapid eye movement sleep disruption and sleep fragmentation are associated with increased orexin-A cerebrospinal-fluid levels in mild cognitive impairment due to Alzheimer’s disease. Neurobiol Aging 40: 120-6. (2016)
Maestri M, Carnicelli L, Tognoni G, Di Coscio E, Giorgi FS, Volpi L, et al. Non-rapid eye movement sleep instability in mild cognitive impairment: a pilot study. Sleep Med 16(9): 1139-45. (2015)
Naismith SL, Hickie IB, Terpening Z, Rajaratnam SM, Hodges JR, Bolitho S, et al. Circadian misalignment and sleep disruption in mild cognitive impairment. J Alzheimers Dis 38(4): 857-66. (2014)
Spira AP, Yager C, Brandt J, Smith GS, Zhou Y, Mathur A, et al. Objectively Measured Sleep and beta-amyloid burden in older Adults: A pilot study. SAGE Open Med 2. (2014)
Westerberg CE, Lundgren EM, Florczak SM, Mesulam MM, Weintraub S, Zee PC, et al. Sleep influences the severity of memory disruption in amnestic mild cognitive impairment: results from sleep self-assessment and continuous activity monitoring. Alzheimer Dis Assoc Disord 24(4): 325-33. (2010)
Westerberg CE, Mander BA, Florczak SM, Weintraub S, Mesulam MM, Zee PC, et al. Concurrent impairments in sleep and memory in amnestic mild cognitive impairment. J Intern Neuropsychol 18(3): 490-500. (2012)
Gorgoni M, Lauri G, Truglia I, Cordone S, Sarasso S, Scarpelli S, et al. Parietal fast sleep spindle density decrease in Alzheimer’s disease and amnesic mild cognitive impairment. Neural Plast 2016: 8376108. (2016)
Newell J, Mairesse O, Verbanck P, Neu D. Is a one-night stay in the lab really enough to conclude? First-night effect and night-to-night variability in polysomnographic recordings among different clinical population samples. Psychiatry Res 200(2-3): 795-801. (2012)
Riedel BW, Winfield CF, Lichstein KL. First night effect and reverse first night effect in older adults with primary insomnia: does anxiety play a role? Sleep Med 2(2): 125-33. (2001)
Apostolova LG, Cummings JL. Neuropsychiatric manifestations in mild cognitive impairment: a systematic review of the literature. Dement Geriatr Cogn Disord 25(2): 115-26. (2008)
Gallagher D, Fischer CE, Iaboni A. Neuropsychiatric symptoms in mild cognitive impairment. Can J Psychiatry 62(3): 161-9. (2017)
Kingshott RN, Douglas NJ. The effect of in-laboratory polysomnography on sleep and objective daytime sleepiness. Sleep 23(8): 1109-13. (2000)
Wams EJ, Wilcock GK, Foster RG, Wulff K. Sleep-wake patterns and cognition of older adults with amnestic mild cognitive impairment (aMCI): a comparison with cognitively healthy adults and moderate Alzheimer’s disease patients. Curr Alzheimer Res 14(10): 1030-41. (2017)
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 25(4): 475-85. (2016)
Cavuoto MG, Ong B, Pike KE, Nicholas CL, Bei B, Kinsella GJ. Better objective sleep quality in older adults with high subjective memory decline. J Alzheimers Dis 53(3): 943-53. (2016)
Cavuoto MG, Ong B, Pike KE, Nicholas CL, Kinsella GJ. Naturalistic prospective memory in older adults: predictors of performance on a habitual task. Neuropsychol Rehabil 27(5): 744-58. (2017)
American Psychiatric Association.. Diagnostic and Statistical Manual of Mental Disorders(4th ed, Text Revision) Washington, DC: American Psychiatric Publishing, Inc. (2000)
Albert MS, DeKosky ST, Dickson D, Dubois B, Feldman HH, Fox NC, et al. The diagnosis of mild cognitive impairment due to Alzheimer’s disease: recommendations from the National Institute on Aging-Alzheimer’s Association workgroups on diagnostic guidelines for Alzheimer’s disease. Alzheimers Dement 7(3): 270-9. (2011)
Wechsler D. Advanced Clinical Solutions for the WAIS-IV and WMS-IVSan Antonio: Pearson. (2009).
Brandt J, Benedict RHB. Hopkins Verbal Learning Test-Revised: Professional ManualLutz, FL: Psychological Assessment Resources. (2001).
Wechsler D. Wechsler Memory Scale - 4th edition (WMS-IV) San Antonio: Harcourt Assessment . (2009).
Lawton MP, Brody EM. Assessment of older people: self-maintaining and instrumental activities of daily living. Gerontologist 9(3): 179-86. (1969)
Folstein MF, Folstein SE, McHugh PR. “Mini-mental state”. A practical method for grading the cognitive state of patients for the clinician. J Psychiatr Res 12(3): 189-98. (1975)
Morris JC. The Clinical Dementia Rating (CDR): current version and scoring rules. Neurology 43(11): 2412-4. (1993)
dos Santos Moraes WA, Poyares DR, Guilleminault C, Ramos LR, Bertolucci PHF, Tufik S. The effect of donepezil on sleep and REM sleep EEG in patients with Alzheimer disease: a double-blind placebo-controlled study. Sleep 29(2): 199-205. (2006)
Lovibond SH, Lovibond PF. Manual for the Depression Anxiety Stress Scales (DASS)Sydney, NSW: Psychology Foundation Monograph. (1993)
Crawford JR, Henry JD. The Depression Anxiety Stress Scales (DASS): normative data and latent structure in a large non-clinical sample. Br J Clin Psychol 42(2): 111-31. (2003)
Tabachnick B, Fidell LS. Using multivariate statisticsfifth edition ed Needham Heights, MA: Allyn & Bacon Boston. (2007)
Hedges LV. Distribution theory for Glass’s estimator of effect size and related estimators. J Educ Stat 6(2): 107-28. (1981)
Cohen J. Statistical power analysis for the behavioral sciences2nd ed Hillsdale, NJ: Lawrence Erlbaum Associates. (1988)
Cohen J. A power primer. Psychol Bull 112(1): 155-9. (1992)
Field A. Discovering statistics using SPSS London: Sage publications. (2005)
Mackinnon DP, Lockwood CM, Williams J. Confidence limits for the indirect effect: distribution of the product and resampling methods. Multivariate Behav Res 39(1): 99. (2004)
Preacher KJ, Hayes AF. Asymptotic and resampling strategies for assessing and comparing indirect effects in multiple mediator models. Behav Res Methods 40(3): 879-91. (2008)
Petersen RC, Lopez O, Armstrong MJ, Getchius TSD, Ganguli M, Gloss D, et al. Practice guideline update summary: Mild cognitive impairment: report of the guideline development, dissemination, and implementation subcommittee of the American Academy of Neurology. Neurology 90(3): 126-35. (2018)
Markesbery WR, Schmitt FA, Kryscio RJ, Davis DG, Smith CD, Wekstein DR. Neuropathologic substrate of mild cognitive impairment. Arch Neurol 63(1): 38-46. (2006)
Song F, Hooper L, Loke Y. Publication bias: what is it? How do we measure it? How do we avoid it? Open Access J Clin Trials 2013(5): 71-81. (2013)
Maxwell SE, Lau MY, Howard GS. Is psychology suffering from a replication crisis? What does “failure to replicate” really mean? Am Psychol 70(6): 487-98. (2015)
Naismith SL, Rogers NL, Lewis SJ, Diamond K, Terpening Z, Norrie L, et al. Sleep disturbance in mild cognitive impairment: differential effects of current and remitted depression. Acta Neuropsychiatr 23(4): 167-72. (2011)
Westwood AJ, Beiser A, Jain N, Himali JJ, DeCarli C, Auerbach SH, et al. Prolonged sleep duration as a marker of early neurodegeneration predicting incident dementia. Neurology 88(12): 1172-9. (2017)
Diamond K, Mowszowski L, Cockayne N, Norrie L, Paradise M, Hermens DF, et al. Randomized controlled trial of a healthy brain ageing cognitive training program: Effects on memory, mood, and sleep. J Alzheimers Dis 44(4): 1181-91. (2015)

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Year: 2019
Page: [233 - 242]
Pages: 10
DOI: 10.2174/1567205016666190301104645
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