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Clinical Manifestations.

Diane M Jacobs1,2, Tyler R Bell3,4, Nathan Whitsel4

  • 1Department of Neurosciences, University of California San Diego, La Jolla, CA, USA.

Alzheimer'S & Dementia : the Journal of the Alzheimer'S Association
|December 26, 2025
PubMed
Summary
This summary is machine-generated.

Subtle cognitive declines in visual short-term memory binding (VSTMB) are linked to reduced locus coeruleus (LC) integrity in older adults with subjective cognitive decline (SCD). This suggests LC integrity is crucial for maintaining cognitive efficiency, even before traditional Alzheimer's disease markers appear.

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Area of Science:

  • Neuroscience
  • Cognitive Psychology
  • Gerontology

Background:

  • Visual short-term memory binding (VSTMB) is vital for cortical connectivity and an early Alzheimer's disease (AD) indicator.
  • Impairments in VSTMB are observed in subjective cognitive decline (SCD) individuals with normal neuropsychological test results.
  • Reduced integrity of the rostral-middle locus coeruleus (LC), implicated in early AD tau accumulation, is linked to SCD.

Purpose of the Study:

  • To investigate the association between VSTMB, subjective cognitive decline (SCD), and locus coeruleus (LC) integrity in cognitively unimpaired older adults.
  • To determine if VSTMB performance, particularly shape-color binding (SCB), is related to LC integrity and self-reported cognitive decline.
  • To explore the role of LC integrity in maintaining cognitive efficiency in the context of early preclinical AD indicators.

Main Methods:

  • Utilized data from the Vietnam Era Twin Study of Aging (N=350) including VSTMB tasks (shape-color binding vs. shape-only), LC-sensitive MRI scans, and Everyday Cognition (ECog) scales.
  • Analyzed VSTMB accuracy using mixed models, regressing performance on LC integrity (LC-CNR) and ECog ratings, controlling for cognitive and psychological factors.
  • Included sensitivity analyses adjusting for global neuropsychological performance to ensure robustness of findings.

Main Results:

  • VSTMB accuracy was lower in the shape-color binding (SCB) condition compared to shape-only (SO), especially at higher set sizes.
  • Higher participant-rated SCD correlated with decreased SCB accuracy relative to SO accuracy.
  • Lower rostral-middle LC integrity (LC-CNR) was associated with poorer SCB accuracy relative to SO accuracy, independent of global cognitive function.

Conclusions:

  • Subtle cognitive efficiency losses in VSTMB are associated with SCD and reduced LC integrity in cognitively unimpaired older adults.
  • LC integrity may be crucial for maintaining cognitive efficiency, potentially compensating for early decline until compensatory capacity is exceeded.
  • Findings highlight the link between LC integrity, SCD, and VSTMB, suggesting potential early preclinical AD markers beyond standard neuropsychological tests.