Sleep Disturbances, Cognitive Status, and Biomarkers of Dementia.

BACKGROUND While sleep disturbances appear to be risk factors in Alzheimer's disease (AD) progression, information such as the prevalence across dementia severity and the influence on the trajectory of cognitive decline is unclear. OBJECTIVE We evaluate the hypotheses that the prevalence of insomnia differs by cognitive impairment, that sleep disturbances track with AD biomarkers, and that longitudinal changes in sleep disorders affect cognition. METHODS We used the National Alzheimer's Coordinating Center Database to determine the prevalence of clinician-identified insomnia and nighttime behaviors in normal, mild cognitive impairment (MCI), and demented individuals. We evaluated mean Montreal Cognitive Assessment (MoCA) scores, hippocampal volumes (HV), and CSF phosphorylated tau:amyloid-β ratios at first visit using analysis of variance with age as a covariate. In longitudinal evaluations, we assessed changes in MoCA scores and HV in insomnia and nighttime behaviors between the first and last visits. RESULTS Prevalence of insomnia was 14%, 16%, and 11% for normal, MCI, and dementia groups. Prevalence of nighttime behaviors was 14%, 21%, and 29% respectively. Insomnia patients had higher MoCA scores, larger HV, and lower pTauBeta than individuals without insomnia, indicating less neurodegeneration. In contrast, nighttime behaviors were associated with worse cognition, smaller HV, and higher pTauBeta. Similar findings were seen between longitudinal associations of sleep disorders and cognition and HV. CONCLUSION Our findings suggest that insomnia is unreliably recognized in patients with cognitive impairment. Nighttime behaviors may better indicate the presence of sleep disturbances and have diagnostic specificity in AD over insomnia.

[1]  Corinne E. Fischer,et al.  Neuropsychiatric Inventory-Questionnaire Assessed Nighttime Behaviors in Cognitively Asymptomatic Patients with Pathologically Confirmed Alzheimer's Disease Predict More Rapid Cognitive Deterioration. , 2022, Journal of Alzheimer's disease : JAD.

[2]  L. Ritterband,et al.  Feasibility and Preliminary Efficacy of an Internet-Delivered Intervention for Insomnia in Individuals with Mild Cognitive Impairment. , 2021, Journal of Alzheimer's disease : JAD.

[3]  S. Naismith,et al.  Sleep-Dependent Memory in Older People With and Without MCI: The Relevance of Sleep Microarchitecture, OSA, Hippocampal Subfields, and Episodic Memory. , 2021, Cerebral cortex.

[4]  N. Rezaei,et al.  The effect of insomnia on development of Alzheimer’s disease , 2020, Journal of neuroinflammation.

[5]  Klaus P. Ebmeier,et al.  Self-reported sleep relates to hippocampal atrophy across the adult lifespan: results from the Lifebrain consortium , 2019, Sleep.

[6]  M. Marsiske,et al.  Optimal cutoffs for the Montreal Cognitive Assessment vary by race and ethnicity , 2018, Alzheimer's & dementia.

[7]  C. Hung,et al.  Risk of dementia in patients with primary insomnia: a nationwide population-based case-control study , 2018, BMC Psychiatry.

[8]  Emmanuel Mignot,et al.  Slow wave sleep disruption increases cerebrospinal fluid amyloid-&bgr; levels , 2017, Brain : a journal of neurology.

[9]  Z. Nasreddine,et al.  Multicenter Validation of an MMSE‐MoCA Conversion Table , 2017, Journal of the American Geriatrics Society.

[10]  W. Jagust,et al.  Sleep: A Novel Mechanistic Pathway, Biomarker, and Treatment Target in the Pathology of Alzheimer's Disease? , 2016, Trends in Neurosciences.

[11]  D. Kansagara,et al.  Management of Chronic Insomnia Disorder in Adults: A Clinical Practice Guideline From the American College of Physicians. , 2016, Annals of internal medicine.

[12]  T. Lai,et al.  The prevalence of neuropsychiatric symptoms in Alzheimer's disease: Systematic review and meta-analysis. , 2016, Journal of affective disorders.

[13]  Daniel J. R. Christensen,et al.  Sleep Drives Metabolite Clearance from the Adult Brain , 2013, Science.

[14]  Philip Scheltens,et al.  Discrepancy between subjective and objective sleep disturbances in early- and moderate-stage Alzheimer disease. , 2012, The American journal of geriatric psychiatry : official journal of the American Association for Geriatric Psychiatry.

[15]  E. Walker,et al.  Diagnostic and Statistical Manual of Mental Disorders , 2013 .

[16]  R. Petersen,et al.  Cerebrospinal fluid biomarker signature in Alzheimer's disease neuroimaging initiative subjects , 2009, Annals of neurology.

[17]  Nathaniel Mercaldo,et al.  The Alzheimer's Disease Centers' Uniform Data Set (UDS): The Neuropsychologic Test Battery , 2009, Alzheimer disease and associated disorders.

[18]  Joylee Wu,et al.  The National Alzheimer's Coordinating Center (NACC) Database: The Uniform Data Set , 2007, Alzheimer disease and associated disorders.

[19]  J. Morris,et al.  The Uniform Data Set (UDS): Clinical and Cognitive Variables and Descriptive Data From Alzheimer Disease Centers , 2006, Alzheimer disease and associated disorders.

[20]  Sonia Ancoli-Israel,et al.  Prevalence and Comorbidity of Insomnia and Effect on Functioning in Elderly Populations , 2005, Journal of the American Geriatrics Society.

[21]  D. Coakley,et al.  Sleep disturbance in mild to moderate Alzheimer's disease. , 2005, Sleep medicine.

[22]  Woodrow D. Deitrich,et al.  The National Alzheimer's Coordinating Center (NACC) Database: An Alzheimer Disease Database , 2004, Alzheimer disease and associated disorders.

[23]  C. Morin,et al.  Validation of the Insomnia Severity Index as an outcome measure for insomnia research. , 2001, Sleep medicine.

[24]  J. Cummings,et al.  Validation of the NPI-Q, a brief clinical form of the Neuropsychiatric Inventory. , 2000, The Journal of neuropsychiatry and clinical neurosciences.

[25]  C. Jack,et al.  Rate of medial temporal lobe atrophy in typical aging and Alzheimer's disease , 1998, Neurology.

[26]  Corinne E. Fischer,et al.  Association between Sleep Disturbances and Medial Temporal Lobe Volume in Older Adults with Mild Cognitive Impairment Free of Lifetime History of Depression. , 2019, Journal of Alzheimer's disease : JAD.

[27]  Wendy F. Cohn,et al.  Effect of a Web-Based Cognitive Behavior Therapy for Insomnia Intervention With 1-Year Follow-up: A Randomized Clinical Trial , 2017, JAMA psychiatry.