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Clinical Manifestations.

Yeshin Kim1, Yaakov Stern2, Na-Young Yeo3

  • 1College of Medicine, Kangwon National University, Chuncheon, Gangwon-do, Korea, Republic of (South).

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

Cognitive reserve (CR) based on phosphorylated tau (pTau) may slow Alzheimer's disease (AD) progression. Individuals with higher pTau-derived CR exhibited slower cognitive decline and a significantly reduced risk of disease stage advancement.

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Area of Science:

  • Neuroscience
  • Biomarkers
  • Neurodegenerative Diseases

Background:

  • Alzheimer's disease (AD) is characterized by amyloid-beta (Aβ) plaques and tau hyperphosphorylation (pTau), leading to neurodegeneration and cognitive decline.
  • Individual variability in clinical outcomes despite similar AD pathology suggests the influence of Cognitive Reserve (CR).
  • Understanding CR at the biomarker level is critical as AD diagnosis increasingly relies on biomarkers like pTau.

Purpose of the Study:

  • To investigate the impact of pTau-derived CR on AD progression.
  • To determine if higher CR is associated with a lower risk of disease progression in AD patients.

Main Methods:

  • Included 695 amyloid-positive participants (Cognitively Unimpaired, Mild Cognitive Impairment, Dementia) with CSF Aβ1-42 and pTau analysis.
  • Measured CR based on pTau (CR_pTau) as the difference between predicted and observed cognitive function (ADAS13).
  • Utilized mixed-effects models and survival analysis to compare disease progression and risk between low-CR_pTau and high-CR_pTau groups.

Main Results:

  • The high CR_pTau group demonstrated significantly slower cognitive decline across all disease stages compared to the low CR_pTau group (p < 0.001).
  • Participants with high CR_pTau had a 45% lower risk of disease stage progression and a 28% lower risk of CDR-SB progression (p < 0.001).
  • A higher proportion of dementia patients were observed in the low CR_pTau group at baseline.

Conclusions:

  • pTau-derived CR significantly influences the rate of AD progression.
  • Higher CR, as indicated by pTau levels, is associated with slower cognitive decline and reduced risk of progression in Alzheimer's disease.
  • These findings highlight the potential of using pTau-based CR as a prognostic biomarker in AD management.