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Clinical Manifestations.

Melina Stark1,2, Elizabeth Kuhn2, Michael Wagner1,2

  • 1Department for Old Age Psychiatry and Cognitive Disorders, University Hospital Bonn, Bonn, Germany.

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

Subjective cognitive decline (SCD) and minor neuropsychological deficits (MNPD) predict Alzheimer's Disease risk. Combining SCD and MNPD identifies individuals at highest risk, optimizing clinical trial recruitment for early-stage AD.

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Area of Science:

  • Neuroscience
  • Clinical Neurology
  • Biostatistics

Background:

  • Recruiting high-risk individuals is vital for early-stage Alzheimer's Disease (AD) clinical trials.
  • Subjective cognitive decline (SCD) and minor neuropsychological deficits (MNPD) indicate increased cognitive decline risk.
  • The combined prognostic value of SCD and MNPD requires further investigation.

Purpose of the Study:

  • To investigate the combined prognostic value of SCD and MNPD in predicting cognitive decline and AD pathology.
  • To assess the utility of SCD and MNPD in stratifying risk for clinical trial participants.
  • To determine the impact of combining SCD and MNPD on required clinical trial sample sizes.

Main Methods:

  • Pooled data from three large cohorts (N=13,192) of cognitively unimpaired individuals.
  • Defined MNPD as median neuropsychological test performance of z≤-0.5.
  • Used Cox and logistic regression to assess associations of SCD/MNPD with MCI, dementia, and biomarker positivity, adjusting for covariates.

Main Results:

  • SCD+/MNPD+ individuals showed the highest risk for progression to MCI (HR=6.23) and dementia.
  • SCD+/MNPD+ and SCD+/MNPD- groups had increased risk of amyloid positivity.
  • SCD+/MNPD+ individuals had increased risk of tau positivity (OR=2.10).
  • Focusing on SCD+/MNPD+ individuals could reduce clinical trial sample size by approximately two-thirds.

Conclusions:

  • SCD and MNPD possess complementary prognostic value in preclinical AD.
  • Individuals with both SCD and MNPD (SCD+/MNPD+) are at particularly high risk for AD pathology and cognitive decline.
  • Incorporating SCD and MNPD assessment is recommended for optimizing clinical trial recruitment in preclinical AD.