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Associations between depression, sleep disturbance, and apolipoprotein E in the development of Alzheimer's disease: dementia

Published online by Cambridge University Press:  29 March 2016

Shanna L. Burke ,
Peter Maramaldi Open the ORCID record for Peter Maramaldi [Opens in a new window] ,
Tamara Cadet  and
Walter Kukull Open the ORCID record for Walter Kukull [Opens in a new window]
Shanna L. Burke*
Affiliation:
Florida International University, Robert Stempel College of Public Health and Social Work, School of Social Work, Miami, FL, USA
Peter Maramaldi
Affiliation:
Simmons College School of Social Work, Boston, MA, USA Oral Health Policy and Epidemiology, Harvard School of Dental Medicine, Boston, MA, USA Department of Social and Behavioral Sciences, Harvard T.H. Chan School of Public Health, Boston, MA, USA
Tamara Cadet
Affiliation:
Simmons College School of Social Work, Boston, MA, USA Oral Health Policy and Epidemiology, Harvard School of Dental Medicine, Boston, MA, USA
Walter Kukull
Affiliation:
National Alzheimer's Coordinating Center (NACC), University of Washington School of Public Health, Department of Epidemiology, Seattle, WA, USA
*
Correspondence should be addressed to: Shanna L. Burke, PhD, MSW, LICSW, Florida International University, Robert Stempel College of Public Health and Social Work, School of Social Work, Modesto A. Maidique Campus, 11200 S.W. 8th Street, AHC5 564, Miami, Florida 33199, USA. Phone: +305-348-7462. Email: [email protected].
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Abstract

Background:

Alzheimer's disease (AD) is a neurodegenerative brain disease that causes cognitive impairment and dementia. Within the US, AD is the most common form of dementia in the elderly, affecting 1 in 10 people over the age of 65. Sleep disturbance has been called a “public health epidemic” and, like depression, is a prodromal symptom of AD but may also contribute to the risk of developing AD. It was hypothesized that sleep disturbance, depression, and the apolipoprotein E (APOE) genotype increase the likelihood of AD.

Methods:

Utilizing data from the National Alzheimer's Coordinating Center, information from evaluations of 11,453 cognitively asymptomatic participants was analyzed. Survival analysis was used to explore the independent relationships between depression, sleep disturbance, and APOE genotypes with eventual AD diagnosis. Cox proportional hazard models were utilized to explore the main effects and synergistic effects of psychosocial factors as moderated by APOE genotypes.

Results:

This study reinforced the association between APOE and AD. The hazard of developing AD was eight times higher for those with recent depression and the Ɛ4 homozygote (HR = 8.15 [3.70–17.95]). Among Ɛ4 carriers with clinician-verified depression, the hazard was ten times that of the reference group (HR = 10.11 [4.43–23.09]). The hazard for Ɛ4 carriers reporting sleep disturbance was almost 7 times greater than the reference group (HR = 6.79 [2.38–19.37]).

Conclusion:

Findings suggest that sleep disturbance, depression, and APOE Ɛ4 genotype are associated with AD during follow-up evaluations among a group of initially cognitively asymptomatic participants. This study contributes to the literature base exploring an increased hazard or risk of AD due to potential modifiable risk factors as well as genetic biomarkers, such as APOE.

Keywords

Alzheimer's diseasedementiadepressionsleep disturbanceapolipoprotein E
Type
Paper of the Month
Information
International Psychogeriatrics , Volume 28 , Issue 9 , September 2016 , pp. 1409 - 1424
Copyright
Copyright © International Psychogeriatric Association 2016 

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References

Aboud, O., Mrak, R. E., Boop, F. and Griffin, S. T. (2012). Apolipoprotein epsilon 3 alleles are associated with indicators of neuronal resilience. BMC Medicine, 10, 35–44. doi:10.1186/1741-7015-10-35.CrossRefGoogle ScholarPubMed
Alzheimer's Association (2015). Alzheimer's disease facts and figures. Alzheimer's & Dementia, 11, 332–384. doi: http://dx.doi.org/10.1016/j.jalz.2015.02.003.CrossRefGoogle Scholar
American Psychiatric Association (1994). Diagnostic and Statistical Manual of Mental Disorders, 4th edn. Washington, DC: American Psychiatric Publishing.Google Scholar
American Psychiatric Association (2013). Diagnostic and Statistical Manual of Mental Disorders, 5th edn. Arlington, VA: American Psychiatric Publishing.Google Scholar
Anderson, K. N. and Bradley, A. J. (2013). Sleep disturbance in mental health problems and neurodegenerative disease. Nature & Science of Sleep, 561–575. doi: 10.2147/NSS.S34842.Google ScholarPubMed
Arnone, D. et al. (2013). State dependent changes in hippocampal grey matter. Molecular Psychiatry, 18, 1265–1272.CrossRefGoogle ScholarPubMed
Ballard, C. Massey, H., Lamb, H. and Morris, C. (1997). Apolipoprotein E: non-cognitive symptoms and cognitive decline in late onset Alzheimer's disease. Journal of Neurology, Neurosurgery & Psychiatry, 63, 273–273. doi: 10.1136/jnnp.63.2.273b CrossRefGoogle ScholarPubMed
Barnes, D. and Yaffe, K. (2011). The projected effect of risk factor reduction on Alzheimer's disease prevalence. Lancet Neurology, 10, 819–828. doi: 10.1016/S1474-4422(11)70145-4.CrossRefGoogle ScholarPubMed
Bateman, R. et al. (2012). Clinical and biomarker changes in dominantly inherited Alzheimer's disease. New England Journal of Medicine, 367, 795–804.CrossRefGoogle ScholarPubMed
Belsky, D. W., Moffitt, T. E. and Caspi, A. (2013). Genetics in population health science: strategies and opportunities. American Journal of Public Health, 103 (S1), S73–S83.CrossRefGoogle ScholarPubMed
Brainerd, C. J., Reyna, V. F., Petersen, R. C., Smith, G. E. and Taub, E. S. (2011). Is the apolipoprotein e genotype a biomarker for mild cognitive impairment? Findings from a nationally representative study. Neuropsychology, 25, 679–689. doi: 10.1037/a0024483.CrossRefGoogle ScholarPubMed
Brainerd, C. J. et al. (2013). The apolipoprotein E genotype predicts longitudinal transitions to mild cognitive impairment but not to Alzheimer's dementia: findings from a nationally representative study. Neuropsychology, 27, 86–94. doi: 10.1037/a0030855.CrossRefGoogle Scholar
Buckley, J. D. (1984). Additive and multiplicative models for relative survival rates. Biometrics, 40, 51–62.CrossRefGoogle ScholarPubMed
Cantillon, M., Barker, W., Harwood, D., Mullan, M. and Duara, R. (1996). Phenotype of depression in Alzheimer's disease (AD) with APOE genotype. Biological Psychiatry, 39, 661.CrossRefGoogle Scholar
Caraci, F., Copani, A., Nicoletti, F. and Drago, F. (2010). Depression and Alzheimer's disease: neurobiological links and common pharmacological targets. European Journal of Pharmacology, 626, 64–71.CrossRefGoogle ScholarPubMed
Centers for Disease Control and Prevention (2013, March). Underlying mortality data provided by national center for health statistics. Retrieved October 27, 2013, from http://www.cdc.gov/nchs/data/databriefs/db116.pdf.Google Scholar
Chui, H. C., Zheng, L., Reed, B. R., Vinters, H. V. and Mack, W. J. (2012). Vascular risk factors and Alzheimer's disease: are these risk factors for plaques and tangles or for concomitant vascular pathology that increases the likelihood of dementia? An evidence-based review. Alzheimer's Research and Therapy, 4, 1–13. doi:10.1186/alzrt98.Google ScholarPubMed
Corder, E. H. et al. (1993). Gene dose of apolipoprotein E type allele and the risk of Alzheimer's disease in late onset families. Science, 261, 921–923.CrossRefGoogle ScholarPubMed
Corder, E. H. et al. (1994). Protective effect of apolipoprotein E type 2 allele for late onset Alzheimer disease. Nature Genetics, 7, 181–184.CrossRefGoogle ScholarPubMed
Cox, D. R. (1972). Regression models and life-tables. Journal of the Royal Statistical Society, Series B, 34, 187–220.Google Scholar
Cummings, J. L. (1997). The neuropsychiatric inventory: assessing psychopathology in dementia patients. Neurology, 48, S10–S16.CrossRefGoogle ScholarPubMed
de-Almada, B. V. P. et al. (2012). Protective effect of the APOE-e3 allele in Alzheimer's disease. Brazilian Journal of Medical and Biological Research, 45, 8–12.CrossRefGoogle ScholarPubMed
de Oliveira, F. F., Ferreira Bertolucci, P. H., Chen, E. S. and Smith, M. C. (2014). Assessment of risk factors for earlier onset of sporadic Alzheimer's disease dementia. Neurology India, 62, 625–630. doi:10.4103/0028-3886.149384.CrossRefGoogle ScholarPubMed
Donix, M., Small, G. W. and Bookheimer, S. Y. (2012). Family history and APOE-4 genetic risk in Alzheimer's disease. Neuropsychological Review, 22, 298–309. doi: 10.1007/s11065-012-9193-2.CrossRefGoogle ScholarPubMed
Efron, B. (1977). The efficiency of Cox's likelihood function for censored data. Journal of the American Statistical Association, 72, 557–565.CrossRefGoogle Scholar
Farrer, L. A. et al. (1997). Effects of age, sex, and ethnicity on the association between apolipoprotein E genotype and Alzheimer disease: a meta-analysis. JAMA, 278, 1349–1356.CrossRefGoogle ScholarPubMed
Fortune, D. A., Lang, R., Cook, S. and Byrd, G. S. (2013). African Americans and Alzheimer's disease: role of health educators in addressing this silent epidemic. American Journal of Health Studies, 28, 92–100.Google Scholar
Ghebranious, N. et al. (2011). A pilot study of gene/gene and gene/environment interactions in Alzheimer disease. Clinical Medicine & Research, 9, 17–25. doi: 10.3I2l/cmr.20I0.894.CrossRefGoogle ScholarPubMed
Gil-Bea, F. J. et al. (2010). HPA axis dysregulation associated to apolipoprotein e4 genotype in Alzheimer's disease. Journal of Alzheimer's Disease, 22, 829–838. doi: 10.3233/JAD-2010-100663.CrossRefGoogle ScholarPubMed
Harwood, D. G., Barker, W. W., Ownby, R. L., Mullan, M. and Duara, R. (2004). No association between subjective memory complaints and apolipoprotein E genotype in cognitively intact elderly. International Journal of Geriatric Psychiatry, 19, 1131–1139. doi:10.1002/gps.1193.CrossRefGoogle ScholarPubMed
Hollingworth, P., Harold, D., Jones, L., Owen, M. J. and Williams, J. (2011). Alzheimer's disease genetics: current knowledge and future challenges. International Journal of Geriatric Psychiatry, 26, 793–802. doi: 10.1002/gps.2628.CrossRefGoogle ScholarPubMed
Hollingworth, P. et al. (2006). Four components describe behavioral symptoms in 1,120 individuals with late-onset Alzheimer's disease. Journal of the American Geriatrics Society, 54, 1348–1354.CrossRefGoogle Scholar
Kaufer, D. I. et al. (2000). Validation of the NPI-Q: a brief clinical form of the neuropsychiatric inventory. The Journal of Neuropsychiatry and Clinical Neurosciences, 12, 233–239.CrossRefGoogle ScholarPubMed
Kleinbaum, D. G. and Klein, M. (2012). Survival Analysis: A Self-Learning Text, 3rd edn. New York: Springer.CrossRefGoogle Scholar
Kumar, A. and Chanana, P. (2014). Sleep reduction: a link to other neurobiological diseases. Sleep and Biological Rhythms, 12, 150–161. doi:10.1111/sbr.12066.CrossRefGoogle Scholar
Lee, H. J. and Dugan, E. (2015). How large is the gap between self-report and assessed mental health and does it impact older adult mental health service utilization?. Journal of Gerontological Social Work, 58, 3–19. doi:10.1080/01634372.2014.919978.CrossRefGoogle Scholar
Lim, A., Yu, L., Kowgier, M., Schneider, J., Buchman, A. and Bennett, D. (2013). Modification of the relationship of the apolipoprotein E ε4 allele to the risk of Alzheimer disease and neurofibrillary tangle density by sleep. JAMA Neurology, 70, 1544–1551. doi:10.1001/jamaneurol.–.4215.CrossRefGoogle Scholar
López-León, S. S. et al. (2008). Meta-analyses of genetic studies on major depressive disorder. Molecular Psychiatry, 13, 772–785. doi:10.1038/sj.mp.4002088.CrossRefGoogle ScholarPubMed
Luciano, M. et al. (2015). Current versus lifetime depression, APOE variation, and their interaction on cognitive performance in younger and older adults. Psychosomatic Medicine, 77, 480–492. doi: 10.1097/PSY.0000000000000190.CrossRefGoogle ScholarPubMed
Lyketsos, C. G. and Olin, J. (2002). Depression in Alzheimer's disease: overview and treatment. Biological Psychiatry, 52, 243–252.CrossRefGoogle ScholarPubMed
Marques, S. F., Oliveira, C. R., Outeiro, T. F. and Pereira, C. F. (2010). Alzheimer's disease: the quest to understand complexity. Journal of Alzheimer's Disease, 21, 373–383. doi:10.3233/JAD2010100303.CrossRefGoogle ScholarPubMed
McKhann, G., Drachman, D., Folstein, M., Katzman, R., Price, D. and Stadlan, E. M. (1984). Clinical diagnosis of Alzheimer's disease: report of the NINCDS-ADRDA Work Group under the auspices of department of health and human services task force on Alzheimer's disease. Neurology, 34, 939–944.CrossRefGoogle ScholarPubMed
McKhann, G. et al. (2011). The diagnosis of dementia due to Alzheimer's disease: recommendations from the national institute on aging-Alzheimer's association workgroups on diagnostic guidelines for Alzheimer's disease. Alzheimer's & Dementia, 7, 263–269. doi:10.1016/j.jalz.2011.03.005.CrossRefGoogle ScholarPubMed
Mendelsohn, A. R. and Larrick, J. W. (2013). Sleep facilitates clearance of metabolites from the brain: glymphatic function in aging and neurodegenerative diseases. Rejuvenation Research, 18, 518–523. doi: 10.1089/rej.2013.1530.CrossRefGoogle Scholar
Meng, X. and D'Arcy, C. (2013). Apolipoprotein E gene, environmental risk factors, and their interactions in dementia among seniors. International Journal of Geriatric Psychiatry, 28, 1005–1014. doi: 10.1002/gps.3918.CrossRefGoogle ScholarPubMed
Morris, J. C. et al. (2006). The uniform data set (UDS): clinical and cognitive variables and descriptive data from Alzheimer's disease centers. Alzheimer Disease and Associated Disorders, 20, 210–216.CrossRefGoogle Scholar
Multhammer, M., Michels, A., Zintl, M., Mendoza, M. C. and Klünemann, H. H. (2014). A large ApoE ε4/ε4 homozygous cohort reveals no association with Parkinson's disease. Acta Neurologica Belgica, 114, 25–31.CrossRefGoogle ScholarPubMed
National Alzheimer's Coordinating Center (2010). The UDS study population. Retrieved from: https://www.alz.washington.edu/WEB/study_pop.html.Google Scholar
Nikodemova, M., Finn, L., Mignot, E., Salzieder, N. and Peppard, P. E. (2013). Association of sleep disordered breathing and cognitive deficit in APOE Ɛ4 carriers. Sleep, 36, 873–880. doi:10.5665/sleep.2714.CrossRefGoogle Scholar
Osorio, R. S. et al. (2014). The interaction between sleep-disordered breathing and apolipoprotein E genotype on cerebrospinal fluid biomarkers for Alzheimer's disease in cognitively normal elderly individuals. Neurobiology of Aging, 35, 1318–1324. doi:10.1016/j.neurobiolaging.2013.12.030.CrossRefGoogle ScholarPubMed
Peavy, G. M. et al. (2007). The effects of prolonged stress and APOE genotype on memory and cortisol in older adults. Biological Psychiatry, 62, 472–478.CrossRefGoogle ScholarPubMed
Pistacchi, M., Gioulis, M., Contin, F., Sanson, F. and Marsala, S. Z. (2014). Sleep disturbance and cognitive disorder: epidemiological analysis in a cohort of 263 patients. Journal of the Neurological Sciences. doi: 10.1007/s10072-014-1870-x.CrossRefGoogle Scholar
Portney, L. G. and Watkins, M. P. (2009). Foundations of Clinical Research: Applications to Practice, 3rd edn. Upper Saddle River, NJ: Pearson Education, Inc.Google Scholar
Qiu, C., Xu, W., Winblad, B. and Fratiglioni, L. (2010). Vascular risk profiles for dementia and Alzheimer's disease in very old people: a population-based longitudinal study. Journal of Alzheimer's Disease, 20, 293–300. doi: 10.3233/JAD-2010-1361.CrossRefGoogle ScholarPubMed
Reitz, C., Tang, M. X., Schupf, N., Manly, J. J., Mayeux, R. and Luchsinger, J. A. (2010). A summary risk score for the prediction of Alzheimer disease in elderly persons. Archives of Neurolology, 67, 835–841. doi: 10.1001/archneurol.2010.136.Google ScholarPubMed
Saunders, A. et al. (1993). Association of apolipoprotein E allele epsilon 4 with late-onset familial and sporadic Alzheimer's disease, Neurology, 43, 1467–1472.CrossRefGoogle ScholarPubMed
Schipper, H. M. (2011). Apolipoprotein E: implications for AD neurobiology, epidemiology and risk assessment. Neurobiology of Aging, 32, 778–790. doi:10.1016/j.neurobiolaging.2009.04.021.CrossRefGoogle ScholarPubMed
Segal, A. Z. (2013). Poor sleep quality may predict preclinical Alzheimer's disease. Neurology Alert, 31, 86–88.Google Scholar
Sheline, Y. I., Gado, M. H. and Kraemer, H. C. (2003) Untreated depression and hippocampal volume loss. American Journal of Psychiatry, 160, 1516–1519.CrossRefGoogle ScholarPubMed
Sperling, R. A. et al. (2011). Toward defining the preclinical stages of Alzheimer's disease: recommendations from the national institute on aging-Alzheimer's association workgroups on diagnostic guidelines for Alzheimer's disease. Alzheimer's & Dementia, 7, 280–292. doi:10.1016/j.jalz.2011.03.003.CrossRefGoogle ScholarPubMed
Spira, A. P. et al. (2013). Self-reported sleep and β-amyloid deposition in community-dwelling older adults. JAMA Neurology, 70, 1537–1543.Google ScholarPubMed
StataCorp (2015). Stata Statistical Software: Release 14. College Station, TX: StataCorp LP.Google Scholar
Talbot, C., Lendon, C., Craddock, N., Shears, S., Morris, J. C. and Goate, A. (1994). Protection against Alzheimer's disease with APOE epsilon 2. Lancet, 343, 1432–1433.CrossRefGoogle ScholarPubMed
Thies, W. and Bleiler, L. (2013). 2013 Alzheimer's disease facts and figures. Alzheimer's & Dementia: The Journal of the Alzheimer's Association, 9, 208–245. doi:10.1016/j.jalz.2013.02.003.Google Scholar
Virta, J. et al. (2013). Midlife sleep characteristics associated with late life cognitive function. Sleep, 36, 1533–1541. doi:10.5665/sleep.3052.CrossRefGoogle ScholarPubMed
Weintraub, S. et al. (2009). The Alzheimer's disease centers’ uniform data set (UDS): the neuropsychological test battery. Alzheimer Disease and Associated Disorders, 23, 91. doi: 10.1097/WAD.0b013e31819c7dd.CrossRefGoogle Scholar
Weldemichael, D. A. and Grossberg, G. T. (2010). Circadian rhythm disturbances in patients with Alzheimer's disease: a review. International Journal of Alzheimer's Disease, 2010, 1–9. doi:10.4061/2010/716453.CrossRefGoogle ScholarPubMed
Xie, L. et al. (2013). Sleep drives metabolite clearance from the adult brain. Science, 342, 373–377. doi:10.1126/science.1241224.CrossRefGoogle ScholarPubMed
Yesavage, J. A. et al. (2004). Sleep/Wake disruption in Alzheimer's disease: APOE status and longitudinal course. Journal of Geriatric Psychiatry & Neurology, 17, 20–24. doi:10.1177/0891988703261994.CrossRefGoogle ScholarPubMed