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Background <p>Alzheimer’s disease (AD) and mild cognitive impairment (MCI) show considerable heterogeneity in treatment response, underscoring the need for individualized therapeutic approaches. Ginkgo biloba extract is commonly used in cognitive disorders, but its efficacy in amyloid biomarker-confirmed populations remains unclear. To evaluate the association between Ginkgo biloba extract exposure and 12-month cognitive and functional change patterns in amyloid PET–positive MCI/AD, and to assess whether baseline plasma MDS-OAβ (amyloid oligomerization tendency) is associated with cognitive trajectory subgroup membership.</p> Methods <p>In this 12-month retrospective study, 165 drug-naïve amyloid PET–positive patients (83 with documented Ginkgo biloba extract use in routine care and 82 without documented Ginkgo use) were assessed for changes in Korean Mini-Mental State Examination (K-MMSE-2), Clinical Dementia Rating–Sum of Boxes (CDR-SB), Korean Instrumental Activities of Daily Living (K-IADL), and plasma MDS-OAβ levels. K-means clustering was used to define three cognitive trajectory subgroups, and exploratory one-vs-rest adjusted logistic regression analyses were performed to examine baseline variables associated with trajectory group membership.</p> Results <p>Three cognitive trajectories were identified: Improver (<i>n</i> = 36), Stabler (<i>n</i> = 113), and Decliner (<i>n</i> = 16). Compared with patients without documented Ginkgo use, patients with documented Ginkgo exposure showed significantly greater cognitive gains (ΔK-MMSE-2 + 1.42 vs. − 0.30, <i>p</i> = 0.012), less IADL decline (<i>p</i> &lt; 0.001), and greater reductions in MDS-OAβ levels (<i>p</i> &lt; 0.001). Baseline plasma MDS-OAβ did not significantly differ among the trajectory groups and was not interpreted as a robust independent predictor of trajectory membership. Ginkgo use differed significantly across trajectory groups and was least frequent in the Decliner group.</p> Conclusions <p>In this amyloid PET–positive MCI/AD cohort, Ginkgo biloba extract exposure was associated with more favorable 12-month cognitive, functional, and plasma MDS-OAβ changes. However, baseline MDS-OAβ should be regarded as an exploratory biomarker rather than a validated predictor of improvement or Ginkgo-related benefit.</p>

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Associations of Ginkgo biloba extract exposure with 12-month cognitive trajectories in amyloid PET–positive mild cognitive impairment and Alzheimer’s disease: a pooled retrospective cohort study

  • 期刊论文

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  • 发表日期：

    2026年7月20日

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  • YoungSoon Yang,
  • Yong Tae Kwak

摘要

Background

Alzheimer’s disease (AD) and mild cognitive impairment (MCI) show considerable heterogeneity in treatment response, underscoring the need for individualized therapeutic approaches. Ginkgo biloba extract is commonly used in cognitive disorders, but its efficacy in amyloid biomarker-confirmed populations remains unclear. To evaluate the association between Ginkgo biloba extract exposure and 12-month cognitive and functional change patterns in amyloid PET–positive MCI/AD, and to assess whether baseline plasma MDS-OAβ (amyloid oligomerization tendency) is associated with cognitive trajectory subgroup membership.

Methods

In this 12-month retrospective study, 165 drug-naïve amyloid PET–positive patients (83 with documented Ginkgo biloba extract use in routine care and 82 without documented Ginkgo use) were assessed for changes in Korean Mini-Mental State Examination (K-MMSE-2), Clinical Dementia Rating–Sum of Boxes (CDR-SB), Korean Instrumental Activities of Daily Living (K-IADL), and plasma MDS-OAβ levels. K-means clustering was used to define three cognitive trajectory subgroups, and exploratory one-vs-rest adjusted logistic regression analyses were performed to examine baseline variables associated with trajectory group membership.

Results

Three cognitive trajectories were identified: Improver (n = 36), Stabler (n = 113), and Decliner (n = 16). Compared with patients without documented Ginkgo use, patients with documented Ginkgo exposure showed significantly greater cognitive gains (ΔK-MMSE-2 + 1.42 vs. − 0.30, p = 0.012), less IADL decline (p < 0.001), and greater reductions in MDS-OAβ levels (p < 0.001). Baseline plasma MDS-OAβ did not significantly differ among the trajectory groups and was not interpreted as a robust independent predictor of trajectory membership. Ginkgo use differed significantly across trajectory groups and was least frequent in the Decliner group.

Conclusions

In this amyloid PET–positive MCI/AD cohort, Ginkgo biloba extract exposure was associated with more favorable 12-month cognitive, functional, and plasma MDS-OAβ changes. However, baseline MDS-OAβ should be regarded as an exploratory biomarker rather than a validated predictor of improvement or Ginkgo-related benefit.