Effects of Konjac glucosylceramides on cognitive function in cognitively unimpaired older adults with subjective cognitive concerns: a randomized, double-blind, controlled pilot study

Abstract

Objectives Diet-derived bioactive lipids may help maintain cognitive resilience during the preclinical stage of Alzheimer’s disease (AD). Konjac-derived glucosylceramide (kGlcCer), traditionally used for skin barrier support, has previously been shown to reduce brain amyloid accumulation in individuals with lower baseline amyloid burden. However, earlier studies used cognitive tests with limited sensitivity. The objective of this study was to investigate whether daily intake of kGlcCer improves cognitive performance and influences amyloid-related biomarkers in cognitively unimpaired older adults with subjective cognitive concerns. Design A 24-week randomized, double-blind, placebo-controlled, parallel-group trial. Participants Forty cognitively unimpaired older adults aged 60–80 years who reported subjective decline in memory or cognitive function were enrolled and randomly assigned to study groups. Intervention Participants received placebo or kGlcCer at doses of 1.8, 3.6, or 5.4 mg/day for 24 weeks. Measurements Cognitive outcomes were assessed using the Wechsler Memory Scale–Revised (WMS-R) Logical Memory I/II, Wechsler Adult Intelligence Scale–Fourth Edition (WAIS-IV) Coding, and Standard Verbal Paired-Associate Learning Test (S-PA). Brain amyloid accumulation was estimated using plasma amyloid-β (Aβ) composite biomarker levels. Results In this exploratory pilot trial, kGlcCer intake was associated with changes in several cognitive measures, although consistent between-group superiority was not observed across all outcomes. The medium-dose group showed significantly greater improvement in WAIS-IV Coding performance compared with the placebo group. Although significant within-group improvements were observed in several measures in the high-dose group such as immediate and delayed verbal memory assessed by WMS-R Logical Memory I/II, as well as in unrelated word-pair learning on the S-PA, consistent placebo-adjusted between-group differences were not observed across these outcomes. Stratified analysis further revealed kGlcCer intake may be associated with favorable changes in amyloid-related biomarkers in high-dose participants with low baseline amyloid burden. No safety concerns related to kGlcCer intake were observed during the study period. Conclusion These exploratory findings suggest that kGlcCer may be associated with changes in selected cognitive domains and amyloid-related biomarkers. However, the present pilot study was not powered to establish efficacy, and larger adequately powered randomized trials are required. Study ID UMIN000051463, date of registration: 07-03-2023.