Content uploaded by Eun Namgung
Author content
All content in this area was uploaded by Eun Namgung on Aug 03, 2021
Content may be subject to copyright.
Effects of Korean red ginseng on human gray matter volume and cognitive function: A voxel‐based morphometry study
Abstract
Objective
We aimed to investigate the effects of Korean red ginseng (KRG) supplementation on gray matter volume of the human brain which could be related to cognitive enhancing effects of KRG.
Methods
In this randomized, double‐blind, placebo‐controlled study, 51 healthy individuals were assigned to receive either KRG (1000 mg/day, n = 26) or placebo (n = 25) for 8 weeks. Gray matter volume of the whole brain was measured using voxel‐based morphometry based on high‐resolution T1‐weighted magnetic resonance images acquired at baseline and week 8. The standardized composite cognitive scores of executive function, attention, and memory were also evaluated at baseline and week 8. Changes in gray matter volume as well as the composite cognitive scores were compared between the KRG and placebo groups.
Results
Following 8 weeks of KRG supplementation, the gray matter volume of the left parahippocampal gyrus increased significantly in the KRG group, relative to the placebo group (p for interaction < 0.001). The KRG group also showed greater magnitude of enhancement in the composite cognitive scores relative to the placebo group (p for interaction = 0.03).
Conclusions
Gray matter volume increase in the parahippocampus may be a key neural change as induced by KRG supplementation, which could be associated with cognitive enhancement.
... Namgung et al. [33] examined the effects of non-standardized Korean red ginseng total extract on brain volume changes and cognitive improvement in healthy adults aged 18-65 years (8 weeks, 1 g/day). They were divided into two groups: 19 placebo and 18 total ginseng extract intake group. ...
... After 8 weeks, they measured the volume changes in the gray matter area of the left parahippocampal gyrus, which plays an important role in memory encoding and retrieval. They found a significant increase in the ginseng total extract intake group compared with the placebo group (z = 2.20, p < 0.03) [33]. Next, they assessed improvements in cognition-related domains such as executive function, attention, and memory between the two groups. ...
... Although there was no significant difference between the placebo and ginseng intake groups in each cognition-related domain such as executive functions, attention and memory, the cognitive domain composite scores of three domains exhibited significant intergroup differences. This indicates that long-term ginseng intake affects brain volume, which is closely related to cognitive function, and that an increase in parahippocampal brain volume may contribute to enhanced cognitive function [33]. ...
Ginseng is a traditional herbal medicine used for prevention and treatment of various diseases as a tonic. Recent scientific cohort studies on life prolongation with ginseng consumption support this record, as those who consumed ginseng for more than 5 years had reduced mortality and cognitive decline compared to those who did not. Clinical studies have also shown that acute or long-term intake of ginseng total extract improves acute working memory performance or cognitive function in healthy individuals and those with subjective memory impairment (SMI), mild cognitive impairment (MCI), or early Alzheimer's disease (AD) dementia who are taking AD medication(s). Ginseng contains various components ranging from classical ginsenosides and polysaccharides to more recently described gintonin. However, it is unclear which ginseng component(s) might be the main candidate that contribute to memory or cognitive improvements or prevent cognitive decline in older individuals. This review describes recent clinical contributors to ginseng components in clinical tests and introduces emerging evidence that ginseng components could be novel candidates for cognitive improvement in older individuals, as ginseng components improve SMI cognition and exhibits add-on effects when co-administered with early AD dementia drugs. The mechanism behind the beneficial effects of ginseng components and how it improves cognition are presented. Additionally, this review shows how ginseng components can contribute to SMI, MCI, or early AD dementia when used as a supplementary food and/or medicine, and proposes a novel combination therapy of current AD medicines with ginseng component(s).
... Moreover, participants in the Ginseng group made fewer errors in a visual memory learning task (PAL subtest) after the intervention. While some studies failed to demonstrate the beneficial effects of red ginseng on performance in cognitive tasks measuring attentional abilities and concentration [29,30], others were able to detect improvements in working memory [29,31], long-term visual memory tasks [30,32], or executive functions [32], which we partially confirmed here on a very high number of participants. Altogether, those results suggest that Red Panax ginseng may exert beneficial effects on certain cognitive functions, particularly those related to spatial planning abilities and visual memory. ...
... Moreover, participants in the Ginseng group made fewer errors in a visual memory learning task (PAL subtest) after the intervention. While some studies failed to demonstrate the beneficial effects of red ginseng on performance in cognitive tasks measuring attentional abilities and concentration [29,30], others were able to detect improvements in working memory [29,31], long-term visual memory tasks [30,32], or executive functions [32], which we partially confirmed here on a very high number of participants. Altogether, those results suggest that Red Panax ginseng may exert beneficial effects on certain cognitive functions, particularly those related to spatial planning abilities and visual memory. ...
Background/objectives: Chronic stress is a pervasive issue affecting individuals worldwide, with profound implications for mental and physical well-being. Panax ginseng, a widely used herbal supplement renowned for its adaptogenic properties, is hypothesized to alleviate some stress effects. This study aims to evaluate the impact of hydroponically grown Red Panax ginseng root powder with a high level of rare ginsenosides supplementation on perceived stress levels, as well as on the emotional and cognitive abilities of moderately stressed participants. Methods: A randomized, double-blind, controlled study was conducted with 149 participants. They were randomly assigned to either the Ginseng supplementation group (N = 72; 200 mg/day, including 24 mg of ginsenosides) or the Placebo group (N = 77). The intervention lasted for 3 weeks. The perceived stress level was measured at baseline (D0) and at the end of the intervention (D21) using a validated scale (PSS) alongside assessments of emotional (BDI and PANAS) and cognitive abilities (CANTAB subtests). Results: Significantly larger decreases in the PSS and negative affect score (PANAS) were observed following intervention in the Ginseng group compared with the Placebo group. Compared to the Placebo group, participants in the Ginseng group showed faster response latencies during a spatial planning task (OTSC subtest). In addition, there was a marginally larger decrease in the BDI score in the Ginseng group. Conclusions: These results confirm the emotional and cognitive benefits of Red Panax ginseng in moderately stressed adults and pave the way for further exploration of its use as a promising approach to improving psychological well-being.
... The ROCF, a commonly used neuropsychological test, examines the integrity of visual memory and visuospatial constructional ability [31,32]. The CVLT serves as another widely accepted neuropsychological assessment, measuring verbal memory and episodic learning [32,33]. ...
... In this study, our emphasis was specifically placed on memory function as the primary cognitive domain of interest, a focus motivated by the fact that memory is one of the earliest cognitive domains impacted by T2DM [33,34]. It is imperative, however, to acknowledge that cognitive dysfunction associated with T2DM may encompass various domains, including executive function, processing speed, and motor function, particularly as the disease advances [4,52]. ...
Cognitive dysfunction, a significant complication of type 2 diabetes mellitus (T2DM), can potentially manifest even from the early stages of the disease. Despite evidence of global brain atrophy and related cognitive dysfunction in early-stage T2DM patients, specific regions vulnerable to these changes have not yet been identified. The study enrolled patients with T2DM of less than five years’ duration and without chronic complications (T2DM group, n=100) and demographically similar healthy controls (control group, n=50). High-resolution T1-weighted magnetic resonance imaging data were subjected to independent component analysis to identify structurally significant components indicative of morphometric networks. Within these networks, the groups’ gray matter volumes were compared, and distinctions in memory performance were assessed. In the T2DM group, the relationship between changes in gray matter volume within these networks and declines in memory performance was examined. Among the identified morphometric networks, the T2DM group exhibited reduced gray matter volumes in both the precuneus (Bonferroni-corrected p=0.003) and insular-opercular (Bonferroni-corrected p=0.024) networks relative to the control group. Patients with T2DM demonstrated significantly lower memory performance than the control group (p=0.001). In the T2DM group, reductions in gray matter volume in both the precuneus (r=0.316, p=0.001) and insular-opercular (r=0.199, p=0.047) networks were correlated with diminished memory performance. Our findings indicate that structural alterations in the precuneus and insular-opercular networks, along with memory dysfunction, can manifest within the first 5 years following a diagnosis of T2DM.
... Additionally, ginseng supplementation improved the cognitive function measured in this study compared with that in the placebo group. The described improvement was significant in subjects who received ginseng but not in those who received placebo [14]. An increase in gray matter volume in the parahippocampus may be a significant neural change resulting from ginseng supplementation, potentially contributing to cognitive enhancement. ...
Background: Ginseng has been used in traditional Chinese medicine for thousands of years as a cure for various diseases. The term “ginseng” is a popular name for herbal drugs that are based on the roots of several distinct species of plants, mainly Korean or Asian ginseng (Panax ginseng C.A. Meyer) and American ginseng (Panax quinquefolius). In this study, we aimed to analyze the health benefits of ginseng. Materials and methods: We analyzed publications found in PubMed and Google Scholar. Articles were selected on the basis of keywords such as “ginseng’’, “Panax ginseng”, “ginsenosides”, and “health benefits”. For the final analysis, the eligible articles were published from 2010--2024. Results: All of the research findings regarding the benefits of ginseng on cognitive function are consistent with their results. Ginseng supplementation has a positive effect on cognition in humans. Seniors are the group of patients who benefit the most from ginseng. Additionally, studies have suggested positive effects on obesity, coronary disease and diabetes. Conclusions: Panax ginseng supplementation can be recommended for patients, as it seems to be relatively safe for them and has several positive effects on health. Further studies are needed to investigate the influence on human health better.
... Research has indicated that ginseng use can help alleviate the cognitive decline. Healthy adults who consumed 1 g/day of KRG for 8 weeks showed an increase in gray matter volume of the left parahippocampal gyrus and improved combined cognitive function, including execution, attention, and memory, compared to the control group (mean age = 40 years, female 76 %) [50]. It is currently unclear if long-term consumption of ginseng can compensate for cognitive deficits caused by low estrogen levels in late life following menopause. ...
Korean Red Ginseng (KRG) has long been used not only as a food supplement but also as a treatment for various diseases. Ginseng originated in South Korea, which later spread to China and Japan, has a wide range of pharmacological activities including immune, endocrine, cardiovascular, and central nervous system effects. KRG is produced by repetitions of steaming and drying of ginseng to extend preservation. During this steaming process, the components of ginseng undergo physio-chemical changes forming a variety of potential active constituents including ginsenoside-Rg3, a unique compound in KRG. Pandemic Coronavirus disease 2019 (COVID-19), has affected both men and women differentially. In particular, women were more vulnerable to COVID-related distress which in turn could aggravate menopause-related disturbances. Complementary and alternative medicinal plants could have aided middle-aged women for several menopause-related symptoms during and post COVID-19 pandemic. This review aimed to explore the beneficial effects of KRG on menopausal symptoms and gynecological cancer.
... Korean Red Ginseng (KRG) is known for its multifaceted health benefits, including antioxidant, anti-inflammatory, and immunestimulating properties [1]. While the majority of research focuses on KRG's impact on the cerebrum, its effects on the cerebellum are not well-documented [2,3]. The challenge lies in selectively assessing the cerebellum's functionality, as current tools cannot isolate it from the cerebral motor region. ...
This study presents a preliminary exploration into the effect of Korean Red Ginseng (KRG) on the cerebellum in individuals with cerebellar atrophy. Over a three month-long period, nine subjects received a 4.5g of KRG daily, with assessments including the ARS, ADAS-Cog, and FDG-PET/CT scans. Results revealed a notable improvement in ataxia and cognitive function without a significant correlation between them. PET/CT scans and SUVR analyses supported these findings, showing an increase in cerebellar glucose uptake after KRG intake. These outcomes suggest a potential pleiotropic effect of KRG on cerebellar function.
Ginseng is a kind of traditional Chinese medicine. It is widely believed that ginseng can improve cognitive function, but its clinical efficacy is still controversial. This study aimed to systematically evaluate the effects of ginseng on cognitive function improvement. This is a systematic review and meta‐analysis of the randomized controlled trials (RCTs). Searching PubMed, Web of Science, the Cochrane Library, and Medline databases to collect RCTs of ginseng on the effects of human cognitive function. The time range is from the establishment of the database to December 2023. The main intervention in the trials was ginseng preparation. The Cochrane risk‐of‐bias tool 2.0 (RoB2.0) and Jadad scale were used to assess the risk of bias and evaluate the quality of the included articles. After data extraction, meta‐analysis was performed using Stata 17.0 software. A total of 15 RCTs were included, and 671 patients were analyzed. The subjects included healthy people, patients of cognitive impairment, schizophrenia, hospitalized, and Alzheimer's disease. The intervention measures were mainly ginseng preparations. The meta‐analysis results indicated that ginseng has a significant effect on memory improvement (SMD = 0.19, 95%CI: 0.02–0.36, p < 0.05), especially at high doses (SMD = 0.33, 95%CI: 0.04–0.61, p < 0.05). Ginseng did not have a positive effect on overall cognition, attention, and executive function (SMD = 0.06, 95%CI: −0.64–0.77, p = 0.86; SMD = 0.06, 95%CI: −0.12 to 0.23, p = 0.54; SMD = −0.03, 95%CI: −0.28 to 0.21, p = 0.79). Ginseng has some positive effects on cognitive improvement, especially on memory improvement. But in the future, more high‐quality studies are needed to determine the effects of ginseng on cognitive function.
Trial Registration: Prospero: CRD42024514231
We aimed to examine the association between the use of specific types of dietary supplements and frailty using cross-sectional, nationally representative survey data. Adults aged ≥50 years in the Korea National Health and Nutrition Examination Survey 2018-2020 were included. We calculated a 46-item frailty index to assess frailty. In total, 27,384 older adults were included (mean age: 62.47 years; median frailty index: 0.12). Among them, 72% used at least one dietary supplement. The prevalence of dietary supplement use was higher among women than among men and in participants with higher socioeconomic status. Compared to non-users, users of dietary supplements had a healthier diet and nutrient intake, and lower levels of frailty. After adjusting for socioeconomic and dietary factors, users of vitamin C, red ginseng or calcium were found to be significantly less frail. Our findings indicate promising results concerning dietary supplement intake in managing frailty among older Korean adults.
Brain plasticity refers to the brain's ability to modify its structure, accompanied by its functional changes. It is influenced by learning, experiences, and dietary factors, even in later life. Accumulated researches have indicated that ginseng may protect the brain and enhance its function in pathological conditions. There is a compelling need for a more comprehensive understanding of ginseng's role in the physiological condition because many individuals without specific diseases seek to improve their health by incorporating ginseng into their routines. This review aims to deepen our understanding of how ginseng affects brain plasticity of people undergoing normal aging process. We provided a summary of studies that reported the impact of ginseng on brain plasticity and related factors in human clinical studies. Furthermore, we explored researches focused on the molecular mechanisms underpinning the influence of ginseng on brain plasticity and factors contributing to brain plasticity. Evidences indicate that ginseng has the potential to enhance brain plasticity in the context of normal aging by mediating both central and peripheral systems, thereby expecting to improve age-related declines in brain function. Moreover, given modern western diet can damage neuroplasticity in the long term, ginseng can be a beneficial supplement for better brain health.
Background
Ginsenoside is the major bioactive component of ginseng, which has been proven to be a neuroprotective drug. The aim of this study was to evaluate the therapeutic effect of ginsenoside in a diabetic Goto-Kakizaki (GK) rat model.
Material/Methods
Twenty GK rats were randomly divided into a diabetic model (DM) group (n=10) and a ginsenoside + DM group (n=10); Wistar rats with the same age and body weight were used as the control (CON) group (n=10). Food and water intake, body weight, and blood fasting plasma glucose were measured. The Morris water maze test was used to detect learning and memory functions of the rats. Superoxide dismutase (SOD), malondialdehyde (MDA), and inflammatory cytokines (TNF-α, IL-1β, and IL-6) in the hippocampus were analyzed after ginsenoside treatment.
Results
The blood glucose, body weight, Morris correlation index, SOD, MDA, and other test results were increased in the diabetic rats. Ginsenoside ameliorated diabetic cognitive decline.
Conclusions
The possible mechanism was related to inhibiting brain oxidative/nitrosative damage and affecting the expression of the cytokines IL-1β, IL-6, and TNF-α.
Longevity in medicine can be defined as a long life without mental or physical deficits. This can be prevented by Alzheimer’s disease (AD). Current conventional AD treatments only alleviate the symptoms without reversing AD progression. Recent studies demonstrated that Panax ginseng extract improves AD symptoms in AD patients and the two main components of ginseng might contribute to AD amelioration. Ginsenosides show various AD-related neuroprotective effects. Gintonin is a newly identified ginseng constituent that contains lysophosphatidic acids (LPAs), and attenuates AD-related brain neuropathies. Ginsenosides decrease amyloid β-protein (Aβ) formation by inhibiting β- and γ-secretase activity or by activating the non-amyloidogenic pathway, inhibit acetylcholinesterase activity and Aβ-induced neurotoxicity, and decrease Aβ-induced production of reactive oxygen species and neuroinflammatory reactions. Oral administration of ginsenosides increases the expression levels of enzymes involved in acetylcholine synthesis in the brain and alleviates Aβ-induced cholinergic deficits in AD models. Similarly, gintonin inhibits Aβ-induced neurotoxicity and activates the non-amyloidogenic pathway to reduce Aβ formation and increase acetylcholine and choline acetyltransferase expression in the brain through LPA receptors. Oral administration of gintonin attenuates brain amyloid plaque deposits, boosting hippocampal cholinergic systems, neurogenesis and thereby ameliorating learning and memory impairments. It also improves cognitive functions in AD patient. Ginsenosides and gintonin attenuate AD-related neuropathology through multiple routes. This review focuses researches demonstrating that ginseng constituents could be a candidate as an adjuvant for AD treatment. However, clinical investigations including efficacy and tolerability analyses may be necessary for the clinical acceptance of ginseng components in combination with conventional AD drugs.
The efficacy and safety of Tremella fuciformis (TF) as a nutritional supplement were assessed in individuals with subjective cognitive impairment (SCI). Seventy-five individuals with SCI were enrolled in an 8-week, randomized, double-blind, placebo-controlled trial of TF (600 mg/day, n = 30 or 1200 mg/day, n = 30) or placebo (n = 15). The primary outcome measure was changes in total scores of the subjective memory complaint questionnaire. The secondary outcome measures were changes in performance on short-term memory and executive functions, which were assessed using standardized cognitive tests. In addition, voxel-based morphometry was performed to examine the effects of TF on changes in gray matter volume. The individuals in the TF group showed greater improvements in the total scores on the subjective memory complaint questionnaire compared with those in the placebo group. There were also significantly greater improvements in short-term memory and executive functions in the TF group relative to the placebo group. Exploratory analysis demonstrated that there were significant group-by-visit interactions on the left precuneus, right supramarginal gyrus, right middle frontal gyrus, and right postcentral gyrus at corrected P < .05. Overall frequency of adverse events did not differ among high-dose TF (40.4%), low-dose TF (35.1%), and placebo groups (41.4%). The current findings suggest that TF could be safely administered to relieve subjective memory complaints and enhance cognition in individuals with SCI.
The role of astrocytes in brain plasticity has not been extensively studied compared with that of neurons. Here we adopted integrative translational and reverse-translational approaches to explore the role of an astrocyte-specific major water channel in the brain, aquaporin-4 (AQP4), in brain plasticity and learning. We initially identified the most prevalent genetic variant of AQP4 (single nucleotide polymorphism of rs162008 with C or T variation, which has a minor allele frequency of 0.21) from a human database (n=60 706) and examined its functionality in modulating the expression level of AQP4 in an in vitro luciferase reporter assay. In the following experiments, AQP4 knock-down in mice not only impaired hippocampal volumetric plasticity after exposure to enriched environment but also caused loss of long-term potentiation after theta-burst stimulation. In humans, there was a cross-sectional association of rs162008 with gray matter (GM) volume variation in cortices, including the vicinity of the Perisylvian heteromodal language area (Sample 1, n=650). GM volume variation in these brain regions was positively associated with the semantic verbal fluency. In a prospective follow-up study (Sample 2, n=45), the effects of an intensive 5-week foreign language (English) learning experience on regional GM volume increase were modulated by this AQP4 variant, which was also associated with verbal learning capacity change. We then delineated in mice mechanisms that included AQP4-dependent transient astrocytic volume changes and astrocytic structural elaboration. We believe our study provides the first integrative evidence for a gliogenetic basis that involves AQP4, underlying language-associated brain plasticity.
Increased expression of brain-derived neurotrophic factor (BDNF) has been associated with memory-enhancing and neuroprotective properties of some drugs under chronic cerebral hypoperfusion (CCH) condition. Ginsenoside Rd (GSRd), one of the main active ingredients in Panax ginseng, is widely used for brain protection. However, it is poorly understood whether epigenetic mechanisms implied in the BDNF modulation after GSRd treatment for CCH remain elusive. Here, we investigated the neuroprotective effects of GSRd and the involved mechanisms. We demonstrated that GSRd administration ameliorated CCH-induced impairment of learning and memory behaviors, evidenced by decreased escape latency and increased number of crossing the platform in Morris water maze test. This improvement was associated with promoted neuron survival and increased BDNF expression in the hippocampus and prefrontal cortex of CCH mice. GSRd improved neuron survival and decreased neuron apoptosis and the level of caspase-3 under oxygen-glucose deprivation/reoxygenation (OGD/R) by upregulation of BDNF as well as in vitro. The levels of acetylated histone H3 (Ac-H3) and histone deacetylase (histone deacetylase 2 (HDAC2)) were altered under OGD/R in a time-dependent manner, and GSRd reestablished the balance between Ac-H3 and HDAC2 which resulted in upregulation of BDNF and increased neuron survival. MS-275, an inhibitor of class I HDACs, abolished the levels of Ac-H3 at the bdnf promoters and enhanced upregulation of BDNF after GSRd administration, suggesting a synergistic effect between GSRd and MS-275. All the data suggested that GSRd provided neuroprotection by epigenetic modulation which accounted for the regulation of BDNF in CCH mice.
Background:
Ginseng has been used to improve brain function and increase longevity. However, little is known about the ingredients of ginseng and molecular mechanisms of its anti-brain aging effects. Gintonin is a novel exogenous ginseng-derived lysophosphatidic acid (LPA) receptor ligand; LPA and LPA1 receptors are involved in adult hippocampal neurogenesis. D-galactose (D-gal) is used to induce brain -aging in animal models because long-term treatment with D-gal facilitates hippocampal aging in experimental adult animals by decreasing hippocampal neurogenesis and inducing learning and memory dysfunction.
Objective:
To investigate the protective effects of gintonin on D-gal-induced hippocampal senescence, impairment of long-term potentiation (LTP), and memory dysfunction.
Methods:
Brain hippocampal aging was induced by D-gal administration (150 mg/kg/day, s.c.; 10 weeks). From the 7th week, gintonin (50 or 100 mg/kg/day, per os) was co-administered with D-gal for 4 weeks. We performed histological analyses, LTP measurements, and object location test.
Results:
Co-administration of gintonin ameliorated D-gal-induced reductions in hippocampal Ki67-immunoreactive proliferating cells, doublecortin-immunoreactive neuroblasts, 5-bromo-2'-deoxyuridine-incorporating NeuN-immunoreactive mature neurons, and LPA1 receptor expression. Co-administration of gintonin in D-gal-treated mice increased the expression of phosphorylated cyclic adenosine monophosphate response element binding protein in the hippocampal dentate gyrus. In addition, co-administration of gintonin in D-gal-treated mice enhanced LTP and restored the cognitive functions compared with those in mice treated with D-gal only.
Conclusion:
These results show that gintonin administration restores D-gal-induced memory deficits by enhancing hippocampal LPA1 receptor expression, LTP, and neurogenesis. Finally, the present study shows that gintonin exerts anti-brain aging effects that are responsible for alleviating brain aging-related dysfunction.
The previous study indicated sesquiterpenoids from the root of Panax ginseng (SPG) exhibited significant antidepressant-like effect, which might be mediated by the modification of the dopaminergic, GABAergic and glutamatergic systems. This study was to investigate SPG’s antidepressant effects and mechanisms on lipopolysaccharide (LPS)-induced depression-like behavior. In the tail suspension test (TST) and forced swimming test (FST), SPG (0.25 and 1 mg/kg, i.g.) and fluoxetine (20 mg/kg, i.p.) effectively reduced the immobility time. SPG treatment significantly reduced serum levels of IL-6 and TNF-α, and increased suppressed SOD activity in hippocampus. In addition, SPG effectively up-regulated the brain-derived neurotrophic factor (BDNF), tropomyosin-related kinase B (TrkB) and sirtuin type 1 (Sirt 1) expression in the hippocampus, down-regulated the inhibitor of kappa B-alpha (IκB-α) and nuclear factor-kappa B (NF-κB) phosphorylation. These results suggested that SPG exhibited antidepressant-like effect through the BDNF/TrkB and Sirt 1/NF-κB signaling pathways.
This randomized, double-blind, placebo-controlled trial examined whether the administration of ganglioside, an active ingredient of deer bone extract, can improve working memory performance by increasing gray matter volume and functional connectivity in the default mode network (DMN) in individuals with subjective cognitive impairment. Seventy-five individuals with subjective cognitive impairment were chosen to receive either ganglioside (330[Formula: see text][Formula: see text]g/day or 660[Formula: see text][Formula: see text]g/day) or a placebo for 8 weeks. Changes in working memory performance with treatment of either ganglioside or placebo were assessed as cognitive outcome measures. Using voxel-based morphometry and functional connectivity analyses, changes in gray matter volume and functional connectivity in the DMN were also assessed as brain outcome measures. Improvement in working memory performance was greater in the ganglioside group than in the placebo group. The ganglioside group, relative to the placebo group, showed greater increases in gray matter volume and functional connectivity in the DMN. A significant relationship between increased functional connectivity of the precuneus and improved working memory performance was observed in the ganglioside group. The current findings suggest that ganglioside has cognitive-enhancing effects in individuals with subjective cognitive impairment. Ganglioside-induced increases in gray matter volume and functional connectivity in the DMN may partly be responsible for the potential nootropic effects of ganglioside. The clinical trial was registered with ClinicalTrials.gov (identifier: NCT02379481).