PMID- 28679595
OWN - NLM
STAT- MEDLINE
DCOM- 20170804
LR  - 20211216
IS  - 1526-632X (Electronic)
IS  - 0028-3878 (Print)
IS  - 0028-3878 (Linking)
VI  - 89
IP  - 5
DP  - 2017 Aug 1
TI  - Poor sleep is associated with CSF biomarkers of amyloid pathology in cognitively 
      normal adults.
PG  - 445-453
LID - 10.1212/WNL.0000000000004171 [doi]
AB  - OBJECTIVE: To determine the relationship between sleep quality and CSF markers of 
      Alzheimer disease (AD) pathology in late midlife. METHODS: We investigated the 
      relationship between sleep quality and CSF AD biomarkers in a cohort enriched for 
      parental history of sporadic AD, the Wisconsin Registry for Alzheimer's 
      Prevention. A total of 101 participants (mean age 62.9 +/- 6.2 years, 65.3% female) 
      completed sleep assessments and CSF collection and were cognitively normal. Sleep 
      quality was measured with the Medical Outcomes Study Sleep Scale. CSF was assayed 
      for biomarkers of amyloid metabolism and plaques (beta-amyloid 42 [Abeta42]), tau 
      pathology (phosphorylated tau [p-tau] 181), neuronal/axonal degeneration (total 
      tau [t-tau], neurofilament light [NFL]), neuroinflammation/astroglial activation 
      (monocyte chemoattractant protein-1 [MCP-1], chitinase-3-like protein 1 
      [YKL-40]), and synaptic dysfunction/degeneration (neurogranin). To adjust for 
      individual differences in total amyloid production, Abeta42 was expressed relative 
      to Abeta40. To assess cumulative pathology, CSF biomarkers were expressed in ratio 
      to Abeta42. Relationships among sleep scores and CSF biomarkers were assessed with 
      multiple regression, controlling for age, sex, time between sleep and CSF 
      measurements, and CSF assay batch. RESULTS: Worse subjective sleep quality, more 
      sleep problems, and daytime somnolence were associated with greater AD pathology, 
      indicated by lower CSF Abeta42/Abeta40 and higher t-tau/Abeta42, p-tau/Abeta42, MCP-1/Abeta42, 
      and YKL-40/Abeta42. There were no significant associations between sleep and NFL or 
      neurogranin. CONCLUSIONS: Self-report of poor sleep was associated with greater 
      AD-related pathology in cognitively healthy adults at risk for AD. Effective 
      strategies exist for improving sleep; therefore sleep health may be a tractable 
      target for early intervention to attenuate AD pathogenesis.
CI  - (c) 2017 American Academy of Neurology.
FAU - Sprecher, Kate E
AU  - Sprecher KE
AD  - From the Department of Medicine and Neuroscience Training Program (K.E.S.) and 
      Wisconsin Alzheimer's Disease Research Center (C.M.C., O.C.O., M.A.S., S.A., 
      S.C.J., B.B.B.), University of Wisconsin-Madison; Wisconsin Alzheimer's Institute 
      (R.L.K., C.M.C., O.C.O., M.A.S., S.A., S.C.J., B.B.B.); Geriatric Research 
      Education and Clinical Center (C.M.C., O.C.O., S.A., S.C.J., B.B.B.), Wm. S. 
      Middleton Veterans Hospital, Madison, WI; Institute of Neuroscience and 
      Physiology (H.Z., K.B.), University of Gothenburg; Clinical Neurochemistry 
      Laboratory (H.Z., K.B.), Sahlgrenska University Hospital, Molndal, Sweden; 
      Department of Molecular Neuroscience (H.Z.), UCL Institute of Neurology, Queen 
      Square, London, UK; and Department of Psychiatry and Human Behavior (R.M.B.), 
      University of California, Irvine. ksprecher@wisc.edu.
FAU - Koscik, Rebecca L
AU  - Koscik RL
AD  - From the Department of Medicine and Neuroscience Training Program (K.E.S.) and 
      Wisconsin Alzheimer's Disease Research Center (C.M.C., O.C.O., M.A.S., S.A., 
      S.C.J., B.B.B.), University of Wisconsin-Madison; Wisconsin Alzheimer's Institute 
      (R.L.K., C.M.C., O.C.O., M.A.S., S.A., S.C.J., B.B.B.); Geriatric Research 
      Education and Clinical Center (C.M.C., O.C.O., S.A., S.C.J., B.B.B.), Wm. S. 
      Middleton Veterans Hospital, Madison, WI; Institute of Neuroscience and 
      Physiology (H.Z., K.B.), University of Gothenburg; Clinical Neurochemistry 
      Laboratory (H.Z., K.B.), Sahlgrenska University Hospital, Molndal, Sweden; 
      Department of Molecular Neuroscience (H.Z.), UCL Institute of Neurology, Queen 
      Square, London, UK; and Department of Psychiatry and Human Behavior (R.M.B.), 
      University of California, Irvine.
FAU - Carlsson, Cynthia M
AU  - Carlsson CM
AD  - From the Department of Medicine and Neuroscience Training Program (K.E.S.) and 
      Wisconsin Alzheimer's Disease Research Center (C.M.C., O.C.O., M.A.S., S.A., 
      S.C.J., B.B.B.), University of Wisconsin-Madison; Wisconsin Alzheimer's Institute 
      (R.L.K., C.M.C., O.C.O., M.A.S., S.A., S.C.J., B.B.B.); Geriatric Research 
      Education and Clinical Center (C.M.C., O.C.O., S.A., S.C.J., B.B.B.), Wm. S. 
      Middleton Veterans Hospital, Madison, WI; Institute of Neuroscience and 
      Physiology (H.Z., K.B.), University of Gothenburg; Clinical Neurochemistry 
      Laboratory (H.Z., K.B.), Sahlgrenska University Hospital, Molndal, Sweden; 
      Department of Molecular Neuroscience (H.Z.), UCL Institute of Neurology, Queen 
      Square, London, UK; and Department of Psychiatry and Human Behavior (R.M.B.), 
      University of California, Irvine.
FAU - Zetterberg, Henrik
AU  - Zetterberg H
AD  - From the Department of Medicine and Neuroscience Training Program (K.E.S.) and 
      Wisconsin Alzheimer's Disease Research Center (C.M.C., O.C.O., M.A.S., S.A., 
      S.C.J., B.B.B.), University of Wisconsin-Madison; Wisconsin Alzheimer's Institute 
      (R.L.K., C.M.C., O.C.O., M.A.S., S.A., S.C.J., B.B.B.); Geriatric Research 
      Education and Clinical Center (C.M.C., O.C.O., S.A., S.C.J., B.B.B.), Wm. S. 
      Middleton Veterans Hospital, Madison, WI; Institute of Neuroscience and 
      Physiology (H.Z., K.B.), University of Gothenburg; Clinical Neurochemistry 
      Laboratory (H.Z., K.B.), Sahlgrenska University Hospital, Molndal, Sweden; 
      Department of Molecular Neuroscience (H.Z.), UCL Institute of Neurology, Queen 
      Square, London, UK; and Department of Psychiatry and Human Behavior (R.M.B.), 
      University of California, Irvine.
FAU - Blennow, Kaj
AU  - Blennow K
AD  - From the Department of Medicine and Neuroscience Training Program (K.E.S.) and 
      Wisconsin Alzheimer's Disease Research Center (C.M.C., O.C.O., M.A.S., S.A., 
      S.C.J., B.B.B.), University of Wisconsin-Madison; Wisconsin Alzheimer's Institute 
      (R.L.K., C.M.C., O.C.O., M.A.S., S.A., S.C.J., B.B.B.); Geriatric Research 
      Education and Clinical Center (C.M.C., O.C.O., S.A., S.C.J., B.B.B.), Wm. S. 
      Middleton Veterans Hospital, Madison, WI; Institute of Neuroscience and 
      Physiology (H.Z., K.B.), University of Gothenburg; Clinical Neurochemistry 
      Laboratory (H.Z., K.B.), Sahlgrenska University Hospital, Molndal, Sweden; 
      Department of Molecular Neuroscience (H.Z.), UCL Institute of Neurology, Queen 
      Square, London, UK; and Department of Psychiatry and Human Behavior (R.M.B.), 
      University of California, Irvine.
FAU - Okonkwo, Ozioma C
AU  - Okonkwo OC
AD  - From the Department of Medicine and Neuroscience Training Program (K.E.S.) and 
      Wisconsin Alzheimer's Disease Research Center (C.M.C., O.C.O., M.A.S., S.A., 
      S.C.J., B.B.B.), University of Wisconsin-Madison; Wisconsin Alzheimer's Institute 
      (R.L.K., C.M.C., O.C.O., M.A.S., S.A., S.C.J., B.B.B.); Geriatric Research 
      Education and Clinical Center (C.M.C., O.C.O., S.A., S.C.J., B.B.B.), Wm. S. 
      Middleton Veterans Hospital, Madison, WI; Institute of Neuroscience and 
      Physiology (H.Z., K.B.), University of Gothenburg; Clinical Neurochemistry 
      Laboratory (H.Z., K.B.), Sahlgrenska University Hospital, Molndal, Sweden; 
      Department of Molecular Neuroscience (H.Z.), UCL Institute of Neurology, Queen 
      Square, London, UK; and Department of Psychiatry and Human Behavior (R.M.B.), 
      University of California, Irvine.
FAU - Sager, Mark A
AU  - Sager MA
AD  - From the Department of Medicine and Neuroscience Training Program (K.E.S.) and 
      Wisconsin Alzheimer's Disease Research Center (C.M.C., O.C.O., M.A.S., S.A., 
      S.C.J., B.B.B.), University of Wisconsin-Madison; Wisconsin Alzheimer's Institute 
      (R.L.K., C.M.C., O.C.O., M.A.S., S.A., S.C.J., B.B.B.); Geriatric Research 
      Education and Clinical Center (C.M.C., O.C.O., S.A., S.C.J., B.B.B.), Wm. S. 
      Middleton Veterans Hospital, Madison, WI; Institute of Neuroscience and 
      Physiology (H.Z., K.B.), University of Gothenburg; Clinical Neurochemistry 
      Laboratory (H.Z., K.B.), Sahlgrenska University Hospital, Molndal, Sweden; 
      Department of Molecular Neuroscience (H.Z.), UCL Institute of Neurology, Queen 
      Square, London, UK; and Department of Psychiatry and Human Behavior (R.M.B.), 
      University of California, Irvine.
FAU - Asthana, Sanjay
AU  - Asthana S
AD  - From the Department of Medicine and Neuroscience Training Program (K.E.S.) and 
      Wisconsin Alzheimer's Disease Research Center (C.M.C., O.C.O., M.A.S., S.A., 
      S.C.J., B.B.B.), University of Wisconsin-Madison; Wisconsin Alzheimer's Institute 
      (R.L.K., C.M.C., O.C.O., M.A.S., S.A., S.C.J., B.B.B.); Geriatric Research 
      Education and Clinical Center (C.M.C., O.C.O., S.A., S.C.J., B.B.B.), Wm. S. 
      Middleton Veterans Hospital, Madison, WI; Institute of Neuroscience and 
      Physiology (H.Z., K.B.), University of Gothenburg; Clinical Neurochemistry 
      Laboratory (H.Z., K.B.), Sahlgrenska University Hospital, Molndal, Sweden; 
      Department of Molecular Neuroscience (H.Z.), UCL Institute of Neurology, Queen 
      Square, London, UK; and Department of Psychiatry and Human Behavior (R.M.B.), 
      University of California, Irvine.
FAU - Johnson, Sterling C
AU  - Johnson SC
AD  - From the Department of Medicine and Neuroscience Training Program (K.E.S.) and 
      Wisconsin Alzheimer's Disease Research Center (C.M.C., O.C.O., M.A.S., S.A., 
      S.C.J., B.B.B.), University of Wisconsin-Madison; Wisconsin Alzheimer's Institute 
      (R.L.K., C.M.C., O.C.O., M.A.S., S.A., S.C.J., B.B.B.); Geriatric Research 
      Education and Clinical Center (C.M.C., O.C.O., S.A., S.C.J., B.B.B.), Wm. S. 
      Middleton Veterans Hospital, Madison, WI; Institute of Neuroscience and 
      Physiology (H.Z., K.B.), University of Gothenburg; Clinical Neurochemistry 
      Laboratory (H.Z., K.B.), Sahlgrenska University Hospital, Molndal, Sweden; 
      Department of Molecular Neuroscience (H.Z.), UCL Institute of Neurology, Queen 
      Square, London, UK; and Department of Psychiatry and Human Behavior (R.M.B.), 
      University of California, Irvine.
FAU - Benca, Ruth M
AU  - Benca RM
AD  - From the Department of Medicine and Neuroscience Training Program (K.E.S.) and 
      Wisconsin Alzheimer's Disease Research Center (C.M.C., O.C.O., M.A.S., S.A., 
      S.C.J., B.B.B.), University of Wisconsin-Madison; Wisconsin Alzheimer's Institute 
      (R.L.K., C.M.C., O.C.O., M.A.S., S.A., S.C.J., B.B.B.); Geriatric Research 
      Education and Clinical Center (C.M.C., O.C.O., S.A., S.C.J., B.B.B.), Wm. S. 
      Middleton Veterans Hospital, Madison, WI; Institute of Neuroscience and 
      Physiology (H.Z., K.B.), University of Gothenburg; Clinical Neurochemistry 
      Laboratory (H.Z., K.B.), Sahlgrenska University Hospital, Molndal, Sweden; 
      Department of Molecular Neuroscience (H.Z.), UCL Institute of Neurology, Queen 
      Square, London, UK; and Department of Psychiatry and Human Behavior (R.M.B.), 
      University of California, Irvine.
FAU - Bendlin, Barbara B
AU  - Bendlin BB
AD  - From the Department of Medicine and Neuroscience Training Program (K.E.S.) and 
      Wisconsin Alzheimer's Disease Research Center (C.M.C., O.C.O., M.A.S., S.A., 
      S.C.J., B.B.B.), University of Wisconsin-Madison; Wisconsin Alzheimer's Institute 
      (R.L.K., C.M.C., O.C.O., M.A.S., S.A., S.C.J., B.B.B.); Geriatric Research 
      Education and Clinical Center (C.M.C., O.C.O., S.A., S.C.J., B.B.B.), Wm. S. 
      Middleton Veterans Hospital, Madison, WI; Institute of Neuroscience and 
      Physiology (H.Z., K.B.), University of Gothenburg; Clinical Neurochemistry 
      Laboratory (H.Z., K.B.), Sahlgrenska University Hospital, Molndal, Sweden; 
      Department of Molecular Neuroscience (H.Z.), UCL Institute of Neurology, Queen 
      Square, London, UK; and Department of Psychiatry and Human Behavior (R.M.B.), 
      University of California, Irvine.
LA  - eng
GR  - R01 AG037639/AG/NIA NIH HHS/United States
GR  - UL1 TR000427/TR/NCATS NIH HHS/United States
GR  - F31 AG048732/AG/NIA NIH HHS/United States
GR  - R01 AG021155/AG/NIA NIH HHS/United States
GR  - R56 AG037639/AG/NIA NIH HHS/United States
GR  - P50 AG033514/AG/NIA NIH HHS/United States
GR  - R01 AG027161/AG/NIA NIH HHS/United States
GR  - R56 AG052698/AG/NIA NIH HHS/United States
PT  - Journal Article
DEP - 20170705
PL  - United States
TA  - Neurology
JT  - Neurology
JID - 0401060
RN  - 0 (Amyloid beta-Peptides)
RN  - 0 (Biomarkers)
RN  - 0 (CCL2 protein, human)
RN  - 0 (CHI3L1 protein, human)
RN  - 0 (Chemokine CCL2)
RN  - 0 (Chitinase-3-Like Protein 1)
RN  - 0 (MAPT protein, human)
RN  - 0 (NGDN protein, human)
RN  - 0 (Neurofilament Proteins)
RN  - 0 (Nuclear Proteins)
RN  - 0 (Peptide Fragments)
RN  - 0 (RNA-Binding Proteins)
RN  - 0 (amyloid beta-protein (1-40))
RN  - 0 (amyloid beta-protein (1-42))
RN  - 0 (neurofilament protein L)
RN  - 0 (tau Proteins)
SB  - IM
CIN - Neurology. 89(5):419. PMID: 28679599
MH  - Amyloid beta-Peptides/cerebrospinal fluid
MH  - Biomarkers/cerebrospinal fluid
MH  - Chemokine CCL2/cerebrospinal fluid
MH  - Chitinase-3-Like Protein 1/cerebrospinal fluid
MH  - Female
MH  - Humans
MH  - Longitudinal Studies
MH  - Male
MH  - Mental Status Schedule
MH  - Middle Aged
MH  - Neurofilament Proteins/cerebrospinal fluid
MH  - Nuclear Proteins/cerebrospinal fluid
MH  - Peptide Fragments/cerebrospinal fluid
MH  - Phosphorylation
MH  - RNA-Binding Proteins
MH  - Self Report
MH  - Sleep/*physiology
MH  - Sleep Wake Disorders/*cerebrospinal fluid/psychology
MH  - tau Proteins/cerebrospinal fluid
PMC - PMC5539733
EDAT- 2017/07/07 06:00
MHDA- 2017/08/05 06:00
PMCR- 2018/02/01
CRDT- 2017/07/07 06:00
PHST- 2016/08/28 00:00 [received]
PHST- 2017/04/14 00:00 [accepted]
PHST- 2017/07/07 06:00 [pubmed]
PHST- 2017/08/05 06:00 [medline]
PHST- 2017/07/07 06:00 [entrez]
PHST- 2018/02/01 00:00 [pmc-release]
AID - WNL.0000000000004171 [pii]
AID - NEUROLOGY2016762302 [pii]
AID - 10.1212/WNL.0000000000004171 [doi]
PST - ppublish
SO  - Neurology. 2017 Aug 1;89(5):445-453. doi: 10.1212/WNL.0000000000004171. Epub 2017 
      Jul 5.