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Correlations between sleep disturbance and brain structures associated with neurodegeneration in the National Alzheimer's Coordinating Center Uniform Data Set

Published:August 12, 2022DOI:https://doi.org/10.1016/j.jocn.2022.07.012

      Highlights

      • Sleep disturbance was associated with greater volumes in the lateral ventricles and greater total white matter hyperintensities.
      • Sleep disturbance was associated with lower mean volumes in 12 hippocampal, frontal, parietal, and temporal lobe regions.
      • Males, Hispanic participants, and those with less formal education were more likely to report sleep disruption.
      • A dementia diagnosis moderated the relationship between sleep disturbance and right and left lateral ventricular volumes.

      Abstract

      This study aimed to 1) determine the association between sleep disturbance and brain structure volumes, 2) the moderation effect of apolipoprotein ε4 genotype on sleep disturbance and brain structures, and 3) the moderation effect of sleep disturbance on cognitive status and regional brain volumes.
      Using the National Alzheimer’s Coordinating Center Uniform Data Set (n = 1,533), multiple linear regressions were used to evaluate the association between sleep disturbance and brain volumes. Sleep disturbance was measured using one question from the NPI-Q.
      After controlling for intracranial volume, age, sex, years of education, race, ethnicity, and applying the FDR correction, total cerebrospinal fluid volume, left lateral ventricle volume, total lateral ventricle volume, and total third ventricle volume demonstrated significantly higher means for those with sleep disturbance. Total brain volume, total white and gray matter volume, total cerebrum brain volume (including gray but not white matter), left hippocampus volume, total hippocampal volume, the left, right, and total frontal lobe cortical gray matter volume, and the left, right, and total temporal lobe cortical gray matter volume demonstrated significantly lower mean volumes for those with sleep disturbance. Sleep disturbance moderated the association between cognitive status and lateral ventricular volumes. These findings suggest that disrupted sleep is associated with atrophy across multiple brain regions and ventricular hydrocephalus ex vacuo.

      Keywords

      Abbreviations:

      AD (Alzheimer's Disease), APOE e4 (apolipoprotein e4)
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      References:

        • Mendelsohn A.R.
        • Larrick J.W.
        Sleep Facilitates Clearance of Metabolites from the Brain: Glymphatic Function in Aging and Neurodegenerative Diseases.
        Rejuvenation Res. 2013; 16: 518-523
        • Demiral Ş.B.
        • et al.
        Apparent diffusion coefficient changes in human brain during sleep - Does it inform on the existence of a glymphatic system?.
        NeuroImage. 2019; 185: 263-273
        • Kang J.-E.
        • et al.
        Amyloid-beta dynamics are regulated by orexin and the sleep-wake cycle.
        Science. 2009; 326: 1005-1007
      1. Brown, B. M. et al. The Relationship between Sleep Quality and Brain Amyloid Burden. Sleep 39, 1063–1068 (2016).

        • Spira A.P.
        • et al.
        Self-reported Sleep and β-Amyloid Deposition in Community-Dwelling Older Adults.
        JAMA Neurol. 2013; 70: 1537-1543
        • Winer J.R.
        • Mander B.A.
        • Kumar S.
        • Reed M.
        • Baker S.L.
        • Jagust W.J.
        • et al.
        Sleep Disturbance Forecasts β-Amyloid Accumulation across Subsequent Years.
        Curr Biol. 2020; 30: 4291-4298.e3
        • Shokri-Kojori E.
        • et al.
        β-Amyloid accumulation in the human brain after one night of sleep deprivation.
        Proc Natl Acad Sci. 2018; 115: 4483-4488
        • Shi L.
        • et al.
        Sleep disturbances increase the risk of dementia: A systematic review and meta-analysis.
        Sleep Med Rev. 2018; 40: 4-16
        • Burke S.L.
        • Maramaldi P.
        • Cadet T.
        • Kukull W.
        Associations between depression, sleep disturbance, and apolipoprotein E in the development of Alzheimer’s disease: dementia.
        Int Psychogeriatr. 2016; 28: 1409-1424
        • Burke S.L.
        • Hu T.
        • Spadola C.E.
        • Burgess A.
        • Li T.
        • Cadet T.
        Treatment of Sleep Disturbance May Reduce the Risk of Future Probable Alzheimer’s Disease.
        J Aging Health. 2019; 31: 322-342
        • Sprecher K.E.
        • Koscik R.L.
        • Carlsson C.M.
        • Zetterberg H.
        • Blennow K.
        • Okonkwo O.C.
        • et al.
        Poor sleep is associated with CSF biomarkers of amyloid pathology in cognitively normal adults.
        Neurology. 2017; 89: 445-453
        • Fjell A.M.
        • McEvoy L.
        • Holland D.
        • Dale A.M.
        • Walhovd K.B.
        What is normal in normal aging? Effects of aging, amyloid and Alzheimer’s disease on the cerebral cortex and the hippocampus.
        Prog Neurobiol. 2014; 117: 20-40
        • Gan L.
        • et al.
        Neurogenic Responses to Amyloid-Beta Plaques in the Brain of Alzheimer’s Disease-Like Transgenic (pPDGF-APPSw, Ind) Mice.
        Neurobiol Dis. 2008; 29: 71-80
      2. Reimann D. et al. Chronic insomnia and MRI-measured hippocampal volumes: a pilot study. Sleep 30, 955–958 (2007).

        • Novati A.
        • Hulshof H.J.
        • Koolhaas J.M.
        • Lucassen P.J.
        • Meerlo P.
        Chronic sleep restriction causes a decrease in hippocampal volume in adolescent rats, which is not explained by changes in glucocorticoid levels or neurogenesis.
        Neuroscience. 2011; 190: 145-155
        • Cross N.E.
        • et al.
        Sleep quality in healthy older people: Relationship with 1H magnetic resonance spectroscopy markers of glial and neuronal integrity.
        Behav Neurosci. 2013; 127: 803-810
      3. Spiegelhalder K. et al. Insomnia does not appear to be associated with substantial structural brain changes. Sleep 36, 731–737 (2013).

        • Winkelman J.W.
        • et al.
        Original Article: Lack of hippocampal volume differences in primary insomnia and good sleeper controls: An MRI volumetric study at 3Tesla.
        Sleep Med. 2010; 11: 576-582
        • Sexton C.E.
        • Storsve A.B.
        • Walhovd K.B.
        • Johansen-Berg H.
        • Fjell A.M.
        Poor sleep quality is associated with increased cortical atrophy in community-dwelling adults.
        Neurology. 2014; 83: 967-973
        • Branger P.
        • et al.
        Relationships between sleep quality and brain volume, metabolism, and amyloid deposition in late adulthood.
        Neurobiol Aging. 2016; 41: 107-114
        • Sprecher K.E.
        • et al.
        Regular article: Amyloid burden is associated with self-reported sleep in nondemented late middle-aged adults.
        Neurobiol Aging. 2015; 36: 2568-2576
        • Corder E.H.
        • et al.
        Gene dose of apolipoprotein E type 4 allele and the risk of Alzheimer9s disease in late onset families.
        Science. 1993; 261: 921-923
        • Wang C.
        • Holtzman D.M.
        Bidirectional relationship between sleep and Alzheimer’s disease: role of amyloid, tau, and other factors.
        Neuropsychopharmacology. 2020; 45: 104-120
        • Lim A.S.P.
        • et al.
        Modification of the Relationship of the Apolipoprotein E ε4 Allele to the Risk of Alzheimer Disease and Neurofibrillary Tangle Density by Sleep.
        JAMA Neurol. 2013; 70: 1544-1551
        • Mander B.A.
        Disturbed Sleep in Preclinical Cognitive Impairment: Cause and Effect?.
        Sleep. 2013; 36: 1275-1276
        • Caselli R.J.
        Obstructive Sleep Apnea, Apolipoprotein E e4, and Mild Cognitive Impairment.
        Sleep Med. 2008; 9: 816-817
      4. Virta JJ. et al. Midlife Sleep Characteristics Associated with Late Life Cognitive Function. Sleep 36, 1533–1541 (2013).

        • Besser L.
        • et al.
        Version 3 of the National Alzheimer’s Coordinating Center’s Uniform Data Set.
        Alzheimer Dis Assoc Disord. 2018; 32: 351
        • Cummings J.
        The Neuropsychiatric Inventory Questionnaire.
        Background and Administration. 1994;
        • Grandner M.A.
        • et al.
        Who Gets the Best Sleep? Ethnic and Socioeconomic Factors Related to Sleep Complaints.
        Sleep Med. 2010; 11: 470-478
        • Alfini A.J.
        • Tzuang M.
        • Owusu J.T.
        • Spira A.P.
        Later-life sleep, cognition, and neuroimaging research: an update for 2020.
        Curr Opin Behav Sci. 2020; 33: 72-77
        • Cheng C.-Y.
        • Tsai C.-F.
        • Wang S.-J.
        • Hsu C.-Y.
        • Fuh J.-L.
        Sleep Disturbance Correlates With White Matter Hyperintensity in Patients With Subcortical Ischemic Vascular Dementia.
        J Geriatr Psychiatry Neurol. 2013; 26: 158-164
        • Sexton C.E.
        • et al.
        Associations between self-reported sleep quality and white matter in community-dwelling older adults: A prospective cohort study.
        Hum Brain Mapp. 2017; 38: 5465-5473
      5. Yaffe K. et al. Sleep Duration and White Matter Quality in Middle-Aged Adults. Sleep 39, 1743–1747 (2016).

        • Ramos A.R.
        • et al.
        Sleep duration is associated with white matter hyperintensity volume in older adults: the Northern Manhattan Study.
        J Sleep Res. 2014; 23: 524-530
        • Prins N.D.
        • Scheltens P.
        White matter hyperintensities, cognitive impairment and dementia: an update.
        Nat Rev Neurol. 2015; 11: 157-165
        • Del Brutto O.H.
        • Mera R.M.
        • Zambrano M.
        • Castillo P.R.
        The association between poor sleep quality and global cortical atrophy is related to age. Results from the Atahualpa Project.
        Sleep Sci. 2016; 9: 147-150
      6. Sterniczuk R, Theou O, Rusak B, Rockwood K. Sleep Disturbance is Associated with Incident Dementia and Mortality. http://www.ingentaconnect.com/content/ben/car/2013/00000010/00000007/art00010 (2013).

      7. Lo JC, Loh KK, Zheng H, Sim SKY, Chee MWL. Sleep Duration and Age-Related Changes in Brain Structure and Cognitive Performance. Sleep 37, 821–821 (2014).

        • Frisoni G.B.
        • Fox N.C.
        • Jack C.R.
        • Scheltens P.
        • Thompson P.M.
        The clinical use of structural MRI in Alzheimer disease.
        Nat Rev Neurol. 2010; 6: 67-77
        • Sheline Y.I.
        Neuroimaging studies of mood disorder effects on the brain.
        Biol Psychiatry. 2003; 54: 338-352
        • Sayo A.
        • Jennings R.G.
        • Van Horn J.D.
        Study factors influencing ventricular enlargement in schizophrenia: a 20 year follow-up meta-analysis.
        NeuroImage. 2012; 59: 154-167
      8. Lim ASP. et al. Regional Neocortical Gray Matter Structure and Sleep Fragmentation in Older Adults. Sleep 39, 227–235 (2016).

        • Liu Y.-R.
        • et al.
        Sleep-related brain atrophy and disrupted functional connectivity in older adults.
        Behav Brain Res. 2018; 347: 292-299
        • Altena E.
        • Vrenken H.
        • Van Der Werf Y.D.
        • van den Heuvel O.A.
        • Van Someren E.J.W.
        Reduced Orbitofrontal and Parietal Gray Matter in Chronic Insomnia: A Voxel-Based Morphometric Study.
        Biol Psychiatry. 2010; 67: 182-185
        • Joo E.Y.
        • Kim H.
        • Suh S.
        • Hong S.B.
        Hippocampal Substructural Vulnerability to Sleep Disturbance and Cognitive Impairment in Patients with Chronic Primary Insomnia: Magnetic Resonance Imaging Morphometry.
        Sleep. 2014; 37: 1189-1198
        • Kreutzmann J.C.
        • Havekes R.
        • Abel T.
        • Meerlo P.
        Sleep deprivation and hippocampal vulnerability: changes in neuronal plasticity, neurogenesis and cognitive function.
        Neuroscience. 2015; 309: 173-190
        • Noh H.J.
        • et al.
        The Relationship between Hippocampal Volume and Cognition in Patients with Chronic Primary Insomnia.
        J Clin Neurol. 2012; 8: 130-138
        • Sabeti S.
        • Al-Darsani Z.
        • Mander B.A.
        • Corrada M.M.
        • Kawas C.H.
        Sleep, hippocampal volume, and cognition in adults over 90 years old.
        Aging Clin Exp Res. 2018; 30: 1307-1318
        • Koo D.L.
        • Shin J.-H.
        • Lim J.-S.
        • Seong J.-K.
        • Joo E.Y.
        Changes in subcortical shape and cognitive function in patients with chronic insomnia.
        Sleep Med. 2017; 35: 23-26
        • Li M.
        • et al.
        Altered gray matter volume in primary insomnia patients: a DARTEL-VBM study.
        Brain Imaging Behav. 2018; 12: 1759-1767
        • Yu S.
        • Feng F.
        • Zhang Q.i.
        • Shen Z.
        • Wang Z.
        • Hu Y.
        • et al.
        Gray matter hypertrophy in primary insomnia: a surface-based morphometric study.
        Brain Imaging Behav. 2020; 14: 1309-1317
        • Chao L.L.
        • Mohlenhoff B.S.
        • Weiner M.W.
        • Neylan T.C.
        Associations between subjective sleep quality and brain volume in Gulf War veterans.
        Sleep. 2014; 37: 445-452
      9. Spira AP. et al. Sleep Duration and Subsequent Cortical Thinning in Cognitively Normal Older Adults. Sleep 39, 1121–1128 (2016).

        • Cho K.
        Chronic ‘jet lag’ produces temporal lobe atrophy and spatial cognitive deficits.
        Nat Neurosci. 2001; 4: 567-568
        • Van Someren E.J.W.
        • et al.
        Medial temporal lobe atrophy relates more strongly to sleep-wake rhythm fragmentation than to age or any other known risk.
        Neurobiol Learn Mem. 2019; 160: 132-138
        • Kahya M.
        • et al.
        The Relationship Between Apolipoprotein ε4 Carrier Status and Sleep Characteristics in Cognitively Normal Older Adults.
        J Geriatr Psychiatry Neurol. 2017; 30: 273-279
        • Drogos L.L.
        • Gill S.J.
        • Tyndall A.V.
        • Raneri J.K.
        • Parboosingh J.S.
        • Naef A.
        • et al.
        Evidence of association between sleep quality and APOE ε4 in healthy older adults: A pilot study.
        Neurology. 2016; 87: 1836-1842
        • Kornblith E.
        • Bahorik A.
        • Boscardin W.J.
        • Xia F.
        • Barnes D.E.
        • Yaffe K.
        Association of Race and Ethnicity With Incidence of Dementia Among Older Adults.
        JAMA. 2022; 327: 1488
        • Mayeda E.R.
        • Glymour M.M.
        • Quesenberry C.P.
        • Whitmer R.A.
        Inequalities in dementia incidence between six racial and ethnic groups over 14 years.
        Alzheimers Dement. 2016; 12: 216-224
        • Fargo K.N.
        • Carrillo M.C.
        • Weiner M.W.
        • Potter W.Z.
        • Khachaturian Z.
        The crisis in recruitment for clinical trials in Alzheimer’s and dementia: An action plan for solutions.
        Alzheimers Dement. 2016; 12: 1113-1115
        • Slopen N.
        • Lewis T.T.
        • Williams D.R.
        Discrimination and sleep: a systematic review.
        Sleep Med. 2016; 18: 88-95
        • Dang-Vu T.T.
        Structural Brain Modifications in Primary Insomnia: Myth or Reality?.
        Sleep. 2013; 36: 965-966