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Clinical Manifestations.

Kelly Rombauts1,2,3, Johan Skoog1,2,3, Tobias Skillbäck1,2,3

  • 1Institute of Neuroscience and Physiology, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.

Alzheimer'S & Dementia : the Journal of the Alzheimer'S Association
|December 25, 2025
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Summary
This summary is machine-generated.

Lower Amyloid-β42/40 (Aβ) levels are linked to faster cognitive processing speed decline in older adults. Women showed a slower cognitive decline rate than men, independent of Aβ levels.

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Area of Science:

  • Neurology
  • Gerontology
  • Biochemistry

Background:

  • Early detection of cognitive decline in preclinical Alzheimer's disease is crucial for intervention.
  • The ratio of Amyloid-β42/40 (Aβ) in cerebrospinal fluid (CSF) is a potential biomarker.
  • Longitudinal studies in population-based cohorts are needed to understand Aβ's role in cognitive aging.

Purpose of the Study:

  • To investigate the association between CSF Aβ42/40 levels and cognitive decline over 5-7 years in 70-year-olds.
  • To examine changes in specific cognitive domains and a composite cognitive score.
  • To explore potential sex differences in cognitive decline rates.

Main Methods:

  • Analysis of CSF Aβ42, Aβ40, t-tau, and p-tau from 250 participants (aged 70 at baseline) in the H70 Gothenburg Birth Cohort Study.
  • Cognitive function assessed using 11 neuropsychological tests across six domains, combined into a composite score.
  • Multiple linear regression models adjusted for age, sex, and education to assess Aβ42/40 associations with cognitive change.

Main Results:

  • Lower CSF Aβ42/40 levels correlated with a steeper decline in processing speed (β=0.123).
  • No significant associations were found between Aβ42/40 and changes in other cognitive domains or the composite score.
  • Women exhibited a slower decline in the composite cognitive score compared to men (β=0.248), independent of Aβ42/40.

Conclusions:

  • Reduced CSF Aβ42/40 may precede broader cognitive decline, specifically impacting processing speed.
  • Cognitive decline progresses slower in women than men between ages 70 and 76.
  • CSF Aβ42/40 ratio is a relevant biomarker for early cognitive changes, particularly processing speed decline.