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Clinical Manifestations.

Kaela A Franco1, Joel Ramirez2,3, Fuqiang Gao2

  • 1Dr. Sandra Black Centre for Brain Resilience and Recovery, Sunnybrook Research Institute, Toronto, ON, Canada.

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

Hippocampal atrophy in neurodegenerative diseases is linked to increased apathy, aberrant behaviors, and poorer sleep quality. These findings highlight the hippocampus's role in emotional regulation and sleep, suggesting compensatory mechanisms in response to brain atrophy.

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Area of Science:

  • Neuroscience
  • Neurology
  • Sleep Medicine

Background:

  • Neurodegenerative diseases causing dementia are associated with hippocampal atrophy, leading to cognitive decline and emotional dysregulation.
  • The hippocampus is vital for memory consolidation and emotional regulation, particularly episodic emotional memories.
  • Behavioral symptoms (apathy, aberrant behaviors) and sleep quality are key concerns in dementia, assessed by the Neuropsychiatric Inventory (NPI) and Pittsburgh Sleep Quality Index (PSQI).

Purpose of the Study:

  • To investigate the correlations between hippocampal volumes and scores on the Neuropsychiatric Inventory (NPI) and Pittsburgh Sleep Quality Index (PSQI) in patients with neurodegenerative diseases.
  • To understand the relationship between hippocampal atrophy and behavioral symptoms like apathy and aberrant behaviors.
  • To explore the association between hippocampal volume and subjective sleep quality.

Main Methods:

  • Retrospective data analysis from the Sunnybrook Dementia Study (SDS) and Ontario Neurodegenerative Disease Research Initiative (ONDRI).
  • Standardized neuroimaging pipeline (HippMapp3r) to measure hippocampal atrophy; whole brain atrophy (BPF) and white matter hyperintensity volumes (WMH) were also assessed.
  • Linear regression and correlation analyses were used to examine associations, controlling for age, sex, education, BPF, and WMH.

Main Results:

  • In the SDS cohort, hippocampal volume was negatively correlated with NPI-Aberrant scores (p=0.029) and NPI-Apathy scores (p=0.007).
  • In the ONDRI cohort, hippocampal volume correlated with poorer sleep quality (PSQI) in Alzheimer's disease/mild cognitive impairment (ADMCI) and cerebrovascular disease (CVD) groups (p<0.0001 and p=0.002, respectively).
  • Smaller hippocampal volumes were associated with longer sleep duration in the ADMCI group (p<0.0001).

Conclusions:

  • Hippocampal atrophy in neurodegenerative diseases may contribute to increased apathy, aberrant behaviors, and altered sleep patterns.
  • Diminished hippocampal volumes might impair emotional regulation and trigger compensatory sleep quality mechanisms.
  • Future research should incorporate objective sleep measures and comprehensive behavioral assessments to further elucidate these relationships.