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Clinical Manifestations.

Neus Falgàs Martínez1, Andrea Val-Guardiola2, Marta Peña3

  • 1Neurology Service, Hospital Clínic de Barcelona and Institut D'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain.

Alzheimer'S & Dementia : the Journal of the Alzheimer'S Association
|December 24, 2025
PubMed
Summary
This summary is machine-generated.

Early-onset Alzheimer's disease (EOAD) patients exhibit poorer sleep quality and reduced locus coeruleus (LC) volume compared to late-onset Alzheimer's disease (LOAD). This suggests subcortical degeneration may drive sleep disturbances in EOAD.

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Area of Science:

  • Neuroscience
  • Neurology
  • Sleep Medicine

Background:

  • Atypical Alzheimer's disease (AD) variants, including early-onset AD (EOAD), present with distinct neuropsychiatric and sleep disturbances.
  • Emerging evidence suggests neuromodulatory subcortical system (NSS) degeneration may underlie these differences.
  • This study investigated sleep patterns and NSS volumes in EOAD versus late-onset AD (LOAD).

Purpose of the Study:

  • To compare sleep-wake patterns and subcortical nucleus volumes between early-onset AD (EOAD) and late-onset AD (LOAD) participants.
  • To explore the relationship between age at onset, atypical AD features, and potential subcortical degeneration.
  • To elucidate the mechanisms driving distinct behavioral and sleep profiles in EOAD.

Main Methods:

  • 113 biomarker-confirmed AD participants (37 EOAD, 76 LOAD) in early stages underwent MRI for subcortical nucleus volume quantification.
  • A subset of 66 participants completed sleep questionnaires (PSQI, ESS) and two weeks of actigraphy.
  • Sleep-wake patterns and circadian rhythms were analyzed using MotionWare software.

Main Results:

  • Actigraphy revealed significantly shorter total sleep time and more fragmented sleep patterns in EOAD compared to LOAD.
  • Subjective sleep assessments (PSQI, ESS) were similar between EOAD and LOAD groups.
  • Locus coeruleus (LC) volume was significantly smaller in EOAD than in LOAD, while other subcortical nuclei showed larger volumes in EOAD.

Conclusions:

  • Objective sleep measures indicate greater sleep disruption in EOAD than LOAD, despite similar subjective reports.
  • Reduced locus coeruleus (LC) volume is a unique finding in EOAD compared to LOAD.
  • These findings underscore the importance of investigating subcortical degeneration in the context of sleep disturbances in early-onset Alzheimer's disease.