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Lower novelty-related locus coeruleus function is associated with Aβ-related cognitive decline in clinically healthy individuals

Author

Listed:
  • Prokopis C. Prokopiou

    (Massachusetts General Hospital, Harvard Medical School)

  • Nina Engels-Domínguez

    (Massachusetts General Hospital, Harvard Medical School
    Maastricht University)

  • Kathryn V. Papp

    (Brigham and Women’s Hospital, Harvard Medical School
    Massachusetts General Hospital, Harvard Medical School)

  • Matthew R. Scott

    (Massachusetts General Hospital, Harvard Medical School
    Boston University)

  • Aaron P. Schultz

    (Massachusetts General Hospital, Harvard Medical School
    Massachusetts General Hospital, Harvard Medical School)

  • Christoph Schneider

    (Massachusetts General Hospital, Harvard Medical School)

  • Michelle E. Farrell

    (Massachusetts General Hospital, Harvard Medical School)

  • Rachel F. Buckley

    (Brigham and Women’s Hospital, Harvard Medical School
    Massachusetts General Hospital, Harvard Medical School
    University of Melbourne)

  • Yakeel T. Quiroz

    (Massachusetts General Hospital, Harvard Medical School
    Massachusetts General Hospital, Harvard Medical School)

  • Georges El Fakhri

    (Massachusetts General Hospital, Harvard Medical School)

  • Dorene M. Rentz

    (Brigham and Women’s Hospital, Harvard Medical School
    Massachusetts General Hospital, Harvard Medical School)

  • Reisa A. Sperling

    (Brigham and Women’s Hospital, Harvard Medical School
    Massachusetts General Hospital, Harvard Medical School)

  • Keith A. Johnson

    (Massachusetts General Hospital, Harvard Medical School
    Brigham and Women’s Hospital, Harvard Medical School
    Massachusetts General Hospital, Harvard Medical School)

  • Heidi I. L. Jacobs

    (Massachusetts General Hospital, Harvard Medical School
    Maastricht University)

Abstract

Animal and human imaging research reported that the presence of cortical Alzheimer’s Disease’s (AD) neuropathology, beta-amyloid and neurofibrillary tau, is associated with altered neuronal activity and circuitry failure, together facilitating clinical progression. The locus coeruleus (LC), one of the initial subcortical regions harboring pretangle hyperphosphorylated tau, has widespread connections to the cortex modulating cognition. Here we investigate whether LC’s in-vivo neuronal activity and functional connectivity (FC) are associated with cognitive decline in conjunction with beta-amyloid. We combined functional MRI of a novel versus repeated face-name paradigm, beta-amyloid-PET and longitudinal cognitive data of 128 cognitively unimpaired older individuals. We show that LC activity and LC-FC with amygdala and hippocampus was higher during novelty. We also demonstrated that lower novelty-related LC activity and LC-FC with hippocampus and parahippocampus were associated with steeper beta-amyloid-related cognitive decline. Our results demonstrate the potential of LC’s functional properties as a gauge to identify individuals at-risk for AD-related cognitive decline.

Suggested Citation

  • Prokopis C. Prokopiou & Nina Engels-Domínguez & Kathryn V. Papp & Matthew R. Scott & Aaron P. Schultz & Christoph Schneider & Michelle E. Farrell & Rachel F. Buckley & Yakeel T. Quiroz & Georges El Fa, 2022. "Lower novelty-related locus coeruleus function is associated with Aβ-related cognitive decline in clinically healthy individuals," Nature Communications, Nature, vol. 13(1), pages 1-14, December.
    • Handle: RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-28986-2
    DOI: 10.1038/s41467-022-28986-2
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    References listed on IDEAS

    as
    1. Mar Yebra & Ana Galarza-Vallejo & Vanesa Soto-Leon & Javier J. Gonzalez-Rosa & Archy O. Berker & Sven Bestmann & Antonio Oliviero & Marijn C. W. Kroes & Bryan A. Strange, 2019. "Action boosts episodic memory encoding in humans via engagement of a noradrenergic system," Nature Communications, Nature, vol. 10(1), pages 1-12, December.
    2. Tae-Ho Lee & Steven G. Greening & Taiji Ueno & David Clewett & Allison Ponzio & Michiko Sakaki & Mara Mather, 2018. "Arousal increases neural gain via the locus coeruleus–noradrenaline system in younger adults but not in older adults," Nature Human Behaviour, Nature, vol. 2(5), pages 356-366, May.
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    4. Martin J. Dahl & Mara Mather & Sandra Düzel & Nils C. Bodammer & Ulman Lindenberger & Simone Kühn & Markus Werkle-Bergner, 2019. "Rostral locus coeruleus integrity is associated with better memory performance in older adults," Nature Human Behaviour, Nature, vol. 3(11), pages 1203-1214, November.
    5. Kathy Y. Liu & Rogier A. Kievit & Kamen A. Tsvetanov & Matthew J. Betts & Emrah Düzel & James B. Rowe & Robert Howard & Dorothea Hämmerer, 2020. "Noradrenergic-dependent functions are associated with age-related locus coeruleus signal intensity differences," Nature Communications, Nature, vol. 11(1), pages 1-9, December.
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