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Clinical Manifestations.

David López-Martos1,2, Mahnaz Shekari1, Gemma Salvadó1,3

  • 1Barcelonaβeta Brain Research Center (BBRC), Pasqual Maragall Foundation, Barcelona, Spain.

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

Amyloid accumulation is linked to specific brain changes in attention, cognitive control, and working memory in individuals at risk for Alzheimer's disease (AD). These findings highlight distinct patterns of cognitive decline preceding AD onset.

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Area of Science:

  • Neuroscience
  • Neurology
  • Cognitive Science

Background:

  • Subtle cognitive decline, particularly in Executive Function (EF), may precede clinical Alzheimer's disease (AD) onset.
  • The relationship between pathological Amyloid (Aβ) accumulation and longitudinal changes in EF remains unclear.
  • Investigating Aβ PET imaging and EF changes in cognitively unimpaired (CU) individuals at risk for AD is crucial.

Purpose of the Study:

  • To investigate longitudinal Aβ accumulation patterns in relation to EF changes in CU individuals at risk for AD.
  • To explore voxel-wise associations between Aβ PET imaging and longitudinal changes in attention, cognitive control, and working memory.
  • To understand the brain regions affected by Aβ accumulation in preclinical AD.

Main Methods:

  • 187 CU individuals from the ALFA+ cohort underwent CSF sampling, longitudinal Aβ PET scans, and neuropsychological assessments.
  • Aβ-positivity was determined by CSF Aβ42/40 ratio; EF changes were assessed using standardized indices for attention, cognitive control, and working memory.
  • Whole-brain voxel-wise linear regression models analyzed change-on-change associations between Aβ accumulation and EF changes.

Main Results:

  • 40.64% of participants were Aβ-positive.
  • Attention decline correlated with parietal and mid-cingulate cortex Aβ accumulation.
  • Cognitive control decline linked to frontal lobe Aβ accumulation; working memory decline associated with parietal and temporal lobe Aβ accumulation.

Conclusions:

  • Distinct regional Aβ accumulation patterns are associated with subtle cognitive decline in attention, cognitive control, and working memory in CU individuals.
  • These findings provide insights into brain regions affected by AD-related EF decline.
  • Tailored neuropsychological assessments are important for monitoring cognitive changes in preclinical AD.