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Clinical Manifestations.

Catherine E Munro1,2, Abigail LaCasse3, Jessie Fanglu Fu4,5

  • 1Harvard Medical School, Boston, MA, USA.

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

In cognitively normal older adults, worsening depressive symptoms combined with high amyloid levels predict decline on the digital clock drawing test (DCT). This highlights vulnerability to cognitive changes even in preclinical stages.

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Area of Science:

  • Neuroscience
  • Gerontology
  • Psychiatry

Background:

  • The digital clock drawing test (DCT) assesses executive functioning, information processing, and visuospatial abilities.
  • DCT performance can differentiate mild cognitive impairment from Alzheimer's disease (AD) dementia and is linked to preclinical AD pathology.
  • Amyloid levels may moderate the relationship between depression and cognitive performance.

Purpose of the Study:

  • To investigate if longitudinal changes in depressive symptoms affect DCT scores.
  • To determine if baseline amyloid levels influence the relationship between depressive symptoms and DCT performance over time.

Main Methods:

  • Ninety cognitively normal older adults from the Harvard Aging Brain Study were assessed.
  • The DCT and Geriatric Depression Scale (GDS) were administered annually over a mean follow-up of 5.7 years.
  • PiB-PET scans measured baseline amyloid levels; regression models analyzed the interaction of GDS slope, time, and amyloid on DCT scores.

Main Results:

  • Depressive symptom slope over time did not significantly predict longitudinal DCT scores on its own.
  • A significant three-way interaction revealed that individuals with higher baseline amyloid burden and increasing depressive symptoms showed declining DCT performance.
  • This interaction indicated a decline in DCT performance over time (beta=-8.78, p=0.004) in this subgroup.

Conclusions:

  • In cognitively normal older adults, elevated baseline amyloid and worsening depressive symptoms are associated with accelerated decline on the DCT.
  • These findings suggest that individuals with both high amyloid and worsening depression are particularly vulnerable to preclinical cognitive decline.
  • Monitoring mood disturbances in older adults, especially those with high amyloid burden, is clinically important for early detection of cognitive changes.