Efficacy and Safety of Choline Alphoscerate for Amnestic Mild Cognitive Impairment: A Randomized Double-Blind Placebo-Controlled Trial

Efficacy and Safety of Choline Alphoscerate for Amnestic Mild Cognitive Impairment: A Randomized Double-Blind Placebo-Controlled Trial | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article Efficacy and Safety of Choline Alphoscerate for Amnestic Mild Cognitive Impairment: A Randomized Double-Blind Placebo-Controlled Trial Jong-Wook Jeon, Su-Young Lee, Seung Hoon Lee, Chang-Woo Han, Geum Duck Park, and 3 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-3488308/v1 This work is licensed under a CC BY 4.0 License Status: Published Journal Publication published 19 Sep, 2024 Read the published version in BMC Geriatrics → Version 1 posted 10 You are reading this latest preprint version Abstract Background Effective interventions for overall healthy subjects with mild cognitive impairment are currently limited. Choline alphoscerate (alpha glyceryl phosphorylcholine, αGPC) is a choline-containing phospholipid used to treat cognitive function impairments in specific neurological conditions. This study aimed to investigate the efficacy and safety of αGPC in individuals diagnosed with mild cognitive impairment. Methods In this multicenter, randomized, placebo-controlled trial, 100 study subjects with mild cognitive impairment underwent double-blind a 727 mg SHCog™ soft capsule (equivalent to 600 mg aGPC) or placebo treatment for 12 weeks. The primary efficacy outcome included changes from baseline on the Alzheimer’s Disease Assessment Scale–cognitive subscale (ADAS-Cog). Safety assessments included regular monitoring of adverse events, and clinical laboratory tests were conducted at baseline and the end of the trial. Results After 12 weeks of αGPC treatment, the ADAS-Cog score decreased by 2.34 points, which was significantly greater than the change observed in the placebo group. No serious AEs were reported, and no study subjects discontinued the intervention because of AEs. There was no significant difference in incidence rate of AEs between the αGPC group and the placebo group. Conclusion This study suggests that αGPC is a safe and effective intervention for improving cognitive function in study subjects with mild cognitive impairment. Trial registration: Clinical Research Information Service; Osong (Chungcheongbuk-do): Korea Centers for Disease Control and Prevention, Ministry of Health and Welfare (Republic of Korea); KCT0008797; A 12-week, multicenter, randomized, double-blind, placebo-controlled human application study to evaluate the efficacy and safety of SH_CAPK08 on cognitive function improvement in mild cognitive decline. mild cognitive impairment choline alphoscerate SHCog™ cognitive function memory language Figures Figure 1 Figure 2 1. Background Dementia is a major global health challenge that imposes substantial societal burdens and costs. According to a report by the World Health Organization in 2021 [ 1 ], the number of people living with dementia was estimated to be approximately 50 million and is anticipated to triple by 2050. Mild cognitive impairment (MCI) is considered a transitional state between normal cognitive aging and dementia [ 2 , 3 ]. MCI is characterized by a noticeable cognitive decline with limited disruption of instrumental activities of daily living but does not meet the criteria for dementia [ 3 ]. In particular, amnestic MCI (aMCI), which features prominent memory impairment, has a higher rate of progression to Alzheimer’s disease (AD) dementia [ 4 ]. The progression rate from MCI to dementia over a short time is 20–40%, with longer-term progression spanning 60–100% over 5–10 years [ 4 , 5 ]. Identifying effective interventions for MCI is important to delay or prevent dementia and improve the quality of life of affected individuals. Numerous pharmacological choices, such as cholinesterase inhibitors and dietary supplements, along with non-pharmacological interventions, such as exercise and cognitive training, have been proposed as potential treatments for MCI [ 6 , 7 , 8 ]. However, clinical trials have yielded inconsistent outcomes, often showing minimal or negligible effects. With respect to cholinesterase inhibitors, the treatment of choice for AD dementia, a previous study demonstrated cognitive improvement of approximately a 1.0-point decrease in the Alzheimer’s Disease Assessment Scale–cognitive subscale (ADAS-cog) score in patients with MCI. However, adverse effects (AEs) in the treatment group were more than double that in the placebo group, and compliance was low (55% of participants who received donepezil) [ 9 ]. In a large-scale randomized control trial (RCT), where the primary outcome measure was the progression rate to AD, no significant difference was observed between the donepezil group and the placebo group, although AEs were significantly more prevalent in the donepezil group [ 10 ]. Because of these reason, regular exercise is the only recommended management option for patients with MCI according to the practical guidelines of the American Academy of Neurology [ 6 ]. Choline alphoscerate (alpha-glyceryl-phosphorylcholine, αGPC) is a choline-containing phospholipid that is often used as a dietary supplement. Choline passes through the blood-brain barrier, which results in increased choline levels. Choline is a precursor of acetylcholine, an essential neurotransmitter for memory and learning. In animal experiments, choline plays a pivotal role in brain development, particularly in hippocampal maturation [ 11 ]. Previous clinical studies have shown that αGPC is effective in managing cognitive decline of vascular origin and in AD dementia [ 12 , 13 , 14 , 15 ]. Further, clinical evidence suggests that choline-enriched multi-nutrient dietary intervention may have a beneficial impact in managing MCI due to AD [ 16 ]. These studies suggest that αGPC may be an effective management intervention for MCI. Therefore, it is important to conduct clinical trials to examine the effects of αGPC on MCI and determine its potential as a viable treatment option. To this end, we conducted a 12-week multicenter, randomized, double-blind, placebo-controlled trial. 2. Methods 2.1 Settings This 12-week, multicenter, randomized, double-blind, placebo-controlled, parallel-group trial was conducted at two hospital sites in the Republic of Korea. The study protocol (versionV1.0, June 24th, 2021) complied with the Declaration of Helsinki and was approved by the Institutional Review Board of the conducting institutions (Yongin Severance Hospital; 9-2021-0085, Myongji Hospital; 2021-07-035). The study is registered in the Clinical Research Information Service. Osong (Chungcheongbuk-do): Korea Centers for Disease Control and Prevention, Ministry of Health and Welfare (Republic of Korea); 2010; 14/09/2023; KCT0008797; A 12-week, multicenter, randomized, double-blind, placebo-controlled human application study to evaluate the efficacy and safety of SHCog™ on cognitive function improvement in mild cognitive decline. 2.2 Study Subject One hundred study subjects were recruited through advertisements. Overall healthy subjects who experienced cognitive decline were tested for aMCI by a certified clinician using neurocognitive tests. Exclusion of dementia were carried out through evaluation by psychiatrists. The inclusion criteria were participants aged between 55 and 85 years old and a decline of 1.0 standard deviation or more in either memory scores (Word List Memory of Word List Recall or Word List Recognition) on the Korean version of the neuropsychological assessment developed by the Consortium to Establish a Registry for Alzheimer’s Disease, or on the Seoul Verbal Learning Test (SVLT) of the Seoul neuropsychological screening battery. The exclusion criteria were as follows: 1) patients with concurrent neurodegenerative conditions, such as AD or Parkinson's disease; 2) current mental disorders (e.g., major depressive disorder, schizophrenia, alcohol use disorder)according to DSM-5 criteria; 3) patients who had taken medications known to affect cognitive function within 4 weeks before the initial visit (all types of psychotropics including antidepressants, nootropics, supplements for brain function) 4) ongoing treatment for severe immune, respiratory, gastrointestinal/hepatic/biliary, renal/urinary, neurological, musculoskeletal, and infectious diseases or malignancies; 5) a history of head trauma with loss of consciousness within 6 months before the initial visit; 6) a history of cardiovascular disease within 6 months before the initial visit; 7) vitamin E supplementation exceeding 400 IU per day or anticipated inability to reduce the dosage; 8) use of estrogen replacement therapy (excluding local applications) within 2 months before the initial visit; 9) use of dietary supplement related to cognitive improvement within 2 months before the initial visit; 10) thyroid disease with thyroid-stimulating hormone (TSH) levels below 0.1 µIU/mL or above 10 µIU/mL; 11) creatinine levels exceeding twice the normal upper limit; 12) aspartate transaminase (AST) or alanine aminotransferase (ALT) levels exceeding three times the normal upper limit; 13) uncontrolled hypertension and diabetes; 14) sensitivity or allergy to the ingredients of the investigational product; 15) pregnancy, breastfeeding, or planning to get pregnant during the study period; 16) participation in any other interventional clinical trial (including clinical trials other than the current study) within 3 months before the initial visit, or planned participation in any other clinical trial (including clinical trials other than the current study) after the start of the current study. All enrolled subjects were provided written informed consent after receiving a complete description of the study protocol. 2.3 Randomization and blinding A block randomization method was used for randomization. To ensure balanced randomization between the αGPC group and the placebo group, the ratio of participants in each group was set to 1:1. The randomization table was generated using the SAS software randomization program, which applied a permutation of random numbers to the sequential test subject numbers, starting from number one. Drug labeling was performed according to the randomization table, and the labeled drugs were supplied to the institutions before the start of the trial. To maintain blinding, the assignment details (information about blinding) for each group were securely managed by the trial coordinator. Except in cases where it was necessary because of significant adverse drug reactions, the blinding codes were not disclosed until the end of the trial. The investigators administered the randomly assigned drug corresponding to the allocated blinding code to the eligible participants during the treatment phase human application phase of the trial. To maintain blinding, reserves (specific to each unique code) were used in cases of shortage or damage to the drugs. Throughout the study, there were no occurrences of unblinding during the trial period. 2.4 Raw Material SHCog™ is a branded α-GPC (HS Bio, Republic of Korea), prepared from Soybean lecithin and is highly viscose, as it absorbs moisture up to 14 ~ 18.5%. Materials used for the manufacturing process and residual solvent standards comply with food regulations of Korea. The raw materials were stored at room temperature until test product is prepared as a soft capsule format. 2.5 Interventions Enrolled subjects were administered αGPC or placebo once daily with adequate water for a duration of 12 weeks. Based on the choline dosage recommended by the National Academies Press, and considering previous studies, a single dose of the drug was determined to contain 727 mg of SHCog™, which is equivalent to 600 mg of aGPC (HSBio, Republic of Korea). Enrolled subjects were allowed to continue taking medications and dietary supplements that were deemed unlikely to affect the interpretation of the results. However, the following medications were prohibited during the trial because of their potential to influence the interpretation of the results: 1) medications that affect cognitive function (e.g., antipsychotics, tricyclic antidepressant, neurodegenerative disease drugs, nootropics) 2) vitamin E supplementation exceeding 400 IU per day, 3) estrogen replacement therapy (excluding local applications), and 4) dietary supplements associated with cognitive improvement. 2.6 Outcome assessments The primary outcome was a change in the total score Alzheimer’s Disease Assessment Scale–cognitive subscale (ADAS-cog score). The Alzheimer Disease Assessment Scale (ADAS) consists of cognitive and noncognitive sections. ADAS-Cog, which is cognitive section of ADAS, aims to assess various cognitive domains in dementia patients, including memory, language abilities, and executive function, among others [ 17 , 18 ]. We additionally assess concentration abilities through an item in noncognitive section. The secondary outcome assessment included the Korean version of the Montreal Cognitive Assessment (MoCA-K) [ 19 ], the Visual Continuous Performance Test (Visual C.P.T) [ 20 ], the Korean-Color Word Stroop Test (K-CWST) [ 21 ], Seoul-Instrumental Activities of Daily Living (S-IADL) [ 22 ], Subjective Cognitive Decline Questionnaire (SCD-Q) [ 23 ], and the Korean version of the Short Form Geriatric Depression Scale (SGDS-K) [ 24 ]. These outcomes were assessed at baseline and 12 weeks after baseline. 2.7 Safety assessment Safety assessments included monitoring of AEs, clinical laboratory tests (hematological/blood chemistry and urinalysis), vital signs (blood pressure and pulse rate), and physical measurements (body weight). These assessments were conducted at screening (2 weeks before baseline), baseline, 6 weeks after baseline, and 12 weeks after baseline. 2.8 Sample size and power analysis A sample size of 35 per treatment group was estimated to assess the effectiveness of αGPC, compared with that of placebo, using primary efficacy variables (ADAS-cog score), with 80% power at a significance level of 0.05. To account for a potential dropout rate of 30%, we enrolled 50 participants in each group, resulting in a total enrollment of 100 individuals across both treatment groups. 2.9 Statistical Analysis Outcome analysis was carried out based on an intention-to-treat (ITT) dataset, defined as the subset of participants who received at least one dose of medication after randomization. The statistical analysis was conducted using SAS® software (Version 9.4, SAS Institute, Cary, North Carolina, USA). To evaluate efficacy variables, including the ADAS-cog score, MoCA-K, visual C.P.T, K-CWST, S-IADL, SCD-Q, and SGDS-K, intra-group comparisons of pre- and post-intake changes were performed using paired t-test. The difference in extent of changes between the αGPC group and the placebo group at each time point was assessed using two sample t-test or Wilcoxon rank-sum test. Demographics and results of biological tests (Laboratory examination, measuring vital signs and body weight) were analyzed using a two-sample t-test or the Wilcoxon rank-sum test. Chi-square or Fisher's exact test was used to analyze categorical data. 3. Results 3.1. Baseline characteristics One hundred subjects were enrolled in this study, of whom 52 received αGPC and 48 received placebo (Fig. 1 ). All 100 subjects were included in the ITT population, whereas 74 subjects (74%) were included in the per-protocol population. For the primary and secondary outcomes, 42 subjects in the αGPC group and 32 subjects in the placebo group were analyzed. Table 1 summarizes baseline characteristics of study participants. The αGPC and placebo groups showed similar distributions in terms of sex, age, education level, smoking and alcohol status, exercise habits, and stress severity. The results of all neuropsychiatric tests are presented in Table 2 . Table 1 Baseline demographic and clinical characteristics of the participants. αGPC (N = 42) Placebo (N = 32) P -value Mean (SD) or N (%) Mean (SD) or N (%) Sex Male 12 (28.57) 8 (25.00) 0.732 Female 30 (71.43) 24 (75.00) Age (years) 70.52 (9.05) 71.75 (8.43) 50–59 7 (16.67) 4 (12.50) 0.555 60–69 11 (26.19) 8 (25.00) 70–79 16 (38.10) 15 (46.88) ≥ 80 8 (19.05) 5 (15.63) Education level No education 3 (7.14) 3 (9.38) 0.866 Elementary school graduate 10 (23.81) 6 (18.75) Middle school graduate 6 (14.29) 3 (9.38) High school graduate 18 (42.86) 13 (40.63) College or University graduate 4 (9.52) 5 (15.63) University postgraduate 1 (2.38) 2 (6.25) Smoking status Never smoker 34 (80.95) 28 (87.50) 0.513 Quit (≥ 1 year) 6 (14.29) 2 (6.25) Quit (< 1 year) 1 (2.38) 0 (0.00) Current smoker 1 (2.38) 2 (6.25) Alcohol intake No 34 (80.95) 25 (78.13) 0.764 Yes 8 (19.05) 7 (21.88) Exercise No 10 (23.81) 1 (3.13) 0.118 1–2 times/week 6 (14.29) 8 (25.00) 3–4 times/week 10 (23.81) 9 (28.13) 5–6 times/week 9 (21.43) 10 (31.25) Daily 7 (16.67) 4 (12.50) Stress severity None 4 (9.52) 6 (18.75) 0.501 Mild 29 (69.05) 20 (62.50) Moderate 8 (19.05) 4 (12.50) Severe 1 (2.38) 2 (6.25) αGPC Choline alphoscerate Table 2 Major results of neuropsychiatric tests before and after 12 weeks of choline alphoscerate (αGPC) and placebo administration αGPC group (N = 42) Placebo group (N = 32) P-value Mean (SD) Mean (SD) Baseline Week 12 Change Baseline Week 12 Change ADAS-cog Total score 10.40 (4.33) 8.06 (4.28) -2.34 (3.26) 9.14 (3.33) 8.17 (3.00) -0.97 (2.32) 0.048 ‡ Memory domain 7.79 (3.43) 6.04 (3.64) -1.75 (2.63) 6.67 (2.20) 6.01 (2.25) -0.66 (1.67) 0.034 ‡ Total score + concentration domain of ADAS-noncog 10.45 (4.30) 8.06 (4.28) -2.39 (3.25) 9.20 (3.39) 8.26 (2.98) -0.94 (2.37) 0.037 ‡ MoCA-K Total score 21.24 (3.74) 22.95 (4.23) 1.71 (2.65) 21.88 (3.75) 22.25 (4.39) 0.38 (2.61) 0.105 § Visuospatial/Executive 3.98 (1.14) 4.21 (0.92) 0.24 (1.03) 4.00 (1.05) 4.09 (0.96) 0.09 (0.89) 0.716 § Attention 4.71 (1.35) 5.00 (1.15) 0.29 (1.27) 5.25 (0.92) 4.94 (1.22) -0.31 (1.35) 0.074 § Language 2.33 (0.82) 2.45 (0.59) 0.12 (0.74) 2.19 (0.82) 2.31 (0.78) 0.13 (0.77) 0.882 § Abstraction 1.00 (0.77) 1.10 (0.82) 0.10 (0.62) 0.97 (0.82) 0.81 (0.78) -0.16 (0.77) 0.102 § Delayed recall 0.86 (0.95) 1.64 (1.65) 0.79 (1.41) 1.00 (1.41) 1.81 (1.73) 0.81 (1.42) 0.844 § Orientation 5.74 (0.54) 5.71 (0.83) -0.02 (0.64) 5.75 (0.62) 5.66 (0.83) -0.09 (0.59) 0.585 § Naming 2.38 (0.94) 2.60 (0.77) 0.21 (0.42) 2.56 (0.76) 2.47 (0.80) -0.09 (0.39) 0.003 § K-CWST Time of word naming (s) 15.35 (3.72) 14.16 (2.79) -1.19 (3.10) 15.21 (5.42) 13.55 (3.20) -1.66 (3.58) 0.548 § Time of color naming (s) 27.64 (12.22) 26.19 (11.99) -1.45 (9.18) 24.57 (12.80) 24.30 (9.49) -0.27 (6.19) 0.048 § Time of congruent word naming (s) 15.33 (3.76) 14.93 (4.23) -0.41 (3.34) 14.96 (5.09) 14.20 (4.42) -0.76 (3.64) 0.832 § Time of incongruent word naming (s) 20.72 (12.43) 20.17 (13.09) -0.55 (7.16) 17.43 (8.75) 17.40 (7.89) -0.03 (5.77) 0.635 § Time of incongruent color naming (s) 72.26 (45.20) 65.90 (47.57) -6.36 (24.36) 60.09 (31.07) 56.37 (30.15) -3.73 (13.47) 0.604 § Error of word naming (n) 0.60 (3.70) 0.00 (0.00) -0.60 (3.70) 0.00 (0.00) 0.03 (0.18) 0.03 (0.18) 0.100 § Error of color naming (n) 0.86 (1.84) 0.67 (1.96) -0.19 (1.52) 0.59 (1.27) 0.47 (0.88) -0.13 (0.87) 0.879 § Error of congruent word naming (n) 0.05 (0.22) 0.07 (0.34) 0.02 (0.41) 0.16 (0.72) 0.06 (0.25) -0.09 (0.78) 0.976 § Error of incongruent word naming (n) 0.19 (0.59) 0.19 (0.63) 0.00 (0.66) 0.16 (0.57) 0.19 (0.47) 0.03 (0.47) 0.603 § Error of incongruent color naming (n) 2.29 (3.13) 1.79 (2.68) -0.50 (1.67) 1.03 (1.64) 0.59 (1.04) -0.44 (1.01) 0.678 § Changes between the baseline and week 12 scores were evaluated within each group using the paired t-test. Change values are highlighted in bold for outcomes that were statistically significant (p < 0.05). Differences in change values between the αGPC and placebo groups were assessed using either the Wilcoxon rank-sum test or the two-sample t-test, and the respective p-values are provided. Statistically significant p-values are shown in bold. ‡: Two sample t-test; §: Wilcoxon rank sum test αGPC Choline alphoscerate ADAS-cog , Alzheimer's Disease Assessment Scale-Cognitive Subscale; MoCA -K , Korean version of the Montreal Cognitive Assessment; K-CWST , Korean-Color Word Stroop Test 3.2. Primary outcome (ADAS-cog score) At baseline, no significant differences were observed in the ADAS-cog scores between the αGPC and placebo groups (p = 0.329). After 12 weeks, the ADAS-cog scores of both groups significantly decreased from baseline (αGPC: -2.34 ± 3.26, p < 0.0001; placebo: -0.97 ± 2.32, p = 0.024). The decrease in the ADAS-cog score was significantly greater in the αGPC group (p < 0.048) than in the placebo group. This difference remained statistically significant even when the ADAS-non-cog concentration score was added to the analysis of ADAS-cog score (p = 0.037). The results are summarized in Table 2 and Fig. 2 . Analysis of the memory domain of the ADAS-cog showed that the difference remained statistically significant (p = 0.034). 3.3. Secondary outcomes 3.3.1 MoCA-K The MoCA-K includes 7 subscales: visuospatial/executive function, language naming, language-sentence repetition, delayed recall (memory index score), attention, abstraction, and orientation. At baseline, no significant difference was observed in the total score of MoCA-K and its subscales between the αGPC and placebo groups. In the αGPC group, there was a significant improvement in the total MoCA-K score from baseline, but the difference in improvement between the two groups was not statistically significant (p = 0.105). Among the subscales, there was a significantly greater improvement in language-naming scores in the αGPC group than in the placebo group (p = 0.003). Both groups showed improvements in memory (delayed recall) score after 12 weeks; however, there was no significant difference in the degree of improvement between the two groups (p = 0.844). The results are summarized in Table 2 and Fig. 2 . 3.3.2 Visual C.P.T Visual C.P.T includes correct response, omission error, commission error, reaction time, and standard deviation of reaction time. At baseline, there was no significant difference in any of the measured subscales in visual C.P.T between the αGPC group and placebo group. After 12 weeks, there was a significant decrease in commission error in the αGPC group and standard deviation of reaction time in both groups. However, there was no significant difference in the degree of improvement in any of the items between the two groups. The results are summarized in Supplementary Table 1 3.3.3 K-CWST In the K-CWST, word reading, color naming, word reading of color words (congruent condition), word reading of color words (incongruent condition), and color naming of color words were analyzed considering duration (time) and error frequency. At baseline, there was no significant difference between the αGPC and placebo groups on any of the measured subscales of the K-CWST. After 12 weeks, there was a significant decrease in word-reading duration (time) in both groups. Regarding the duration (time) of color naming, there was a significant difference in the decrease between the two groups (p = 0.048). The results are summarized in Table 2 . 3.3.4 S-IADL S-IADL included potential capacity and current performance. At baseline, no significant differences were observed in both potential capacity and current performance between the αGPC group and placebo group. After 12 weeks, there was a significant decrease in potential capacity in both groups; however, no significant difference was observed in the degree of decrease between the two groups (p = 0.467). The results are summarized in Supplementary Table 1 3.3.5 SCD-Q At baseline, no significant difference in SCD-Q was observed between the αGPC and placebo groups. After 12 weeks, there was a significant decrease in both groups; however, no significant difference was observed in the degree of decrease between the two groups (p = 0.343). The results are summarized in Supplementary Table 1 3.3.6 SGDS-K At baseline, no significant difference in SGDS-K was observed between the αGPC and placebo groups. After 12 weeks, there was a significant decrease in both groups; however, there was no significant difference in the degree of decrease between the two groups (p = 0.560). The results are summarized in Supplementary Table 1 3.4 Adverse events and safety No serious AEs were reported, and no participants discontinued the intervention because of AEs. The most common AEs in both the αGPC and placebo groups were gastrointestinal problems, such as abdominal pain, constipation, dyspepsia, and nausea. All AEs reported in both groups resolved completely. Lists of AEs are presented in Supplementary Table 2. In terms of blood chemistry, uric acid showed a significant increase when compared to the placebo group (p = 0.024). Total cholesterol also exhibited a rising trend compared to the placebo group (p = 0.033). However, there were no clinically meaningful changes observed in the test group. Results of biological tests are presented in Supplementary Table 3. 4. Discussion This is the first study on αGPC to explore the safety, tolerability, and efficacy of αGPC in overall healthy individuals with concern of MCI. The results show that αGPC is safe and effective in improving cognitive functions in MCI. The decrease in ADAS-cog score was significantly greater at the 12 weeks post-treatment follow-up assessment in the αGPC group than in the placebo group. A 727 mg dose of SHCog™ (600 mg aGPC) once daily was well tolerated by the test group. No serious AEs occurred, and the most frequent side effects included gastrointestinal problems, such as abdominal pain, constipation, dyspepsia, and nausea. However, no significant differences in symptoms were observed between the two groups. The primary outcome, the ADAS-cog score, showed an average decrease of 2.34 points from baseline after 12 weeks of oral αGPC administration, which was significantly greater than that in the placebo group. The 2.34-point decrease at 12 weeks in our study indicated a slightly greater cognitive improvement than that observed at 12 weeks (decrease of 1.5–2.0 ADAS-cog score) in a RCT investigating the effects of 48 weeks of donepezil treatment [ 9 ]. In a 24-week RCT study investigating the effects of regular exercise on study subjects with MCI, the ADAS-cog score decreased by an average of 1.2 points at the endpoint [ 25 ]. While the shorter duration of our study makes it difficult to make direct comparisons with these studies, the improvement in ADAS-cog observed in our study suggests comparable effectiveness. Analysis of the memory domain of the ADAS-cog revealed a significant improvement, compared with that of the placebo group. Previous RCTs investigating the effects of choline supplementation (Citicoline) in older adults with memory problems demonstrated significant enhancements in memory function [ 26 ]. Another RCT investigating multi-nutrition, including choline, in prodromal AD also revealed significant improvements in the memory domain [ 16 ]. A review of the effects of αGPC on individuals with cognitive decline highlighted the efficacy of αGPC in memory and attention domains [ 12 ]. The observed enhancement of memory function by αGPC in our study aligns with these previous findings. Considering the significant relevance of memory decline, particularly in the progression from MCI to AD [ 6 ], the memory-enhancing effect of αGPC has crucial clinical significance. Among the secondary outcome measures in our study, significant improvements in the language-naming subscale of the MoCA-K and the duration (time) of color naming in the K-SVLT were observed in the αGPC group, compared to that in the placebo group. This suggests that αGPC has a particular impact on the language and attention domains. A prospective study evaluating the effects of αGPC on speech recognition in patients with age-related hearing loss indicated its clinical efficacy in central language comprehension, beyond peripheral audibility [ 27 ]. A review of the effects of αGPC on patients with dementia highlighted the effect of αGPC on the attention domain [ 12 ]. The outcomes of our study provide supporting evidence for existing studies on language and attention functions. No serious adverse events or drug discontinuation due to AEs were reported in our study. In contrast, an RCT assessing the effects of donepezil on patients with MCI reported drug discontinuation by 42% (165 out of 391) of patients in the donepezil group, with nearly half of them (72 individuals) discontinuing treatment because of AEs [ 9 ]. Therefore, the tolerability of αGPC observed in our study might be relatively favorable. Our study results provide additional evidence supporting previous research findings that αGPC possesses a favorable safety profile [ 28 ]. After 12 weeks of αGPC intake, there was an increase in uric acid and cholesterol levels; however, no subject showed clinically significant changes [ 29 ]. Nevertheless, recent cohort studies have reported an association with stroke [ 30 ], long-term monitoring will be necessary for future research. Our study has several limitations. First, the 12-week duration was not enough to capture the full spectrum of αGPC's potential effects on MCI. Cognitive changes could manifest over a more extended period. Furthermore, because of the short study period, there is the possibility of a learning effect. Both the placebo and αGPC groups showed significant ADAS-cog score improvements from baseline to the endpoint. The improvement in the placebo group suggests an increased familiarity with the assessment process over time, regardless of treatment. While the change in the αGPC group was significantly larger, it is noteworthy that the reported 2.34-point reduction might have been influenced by the learning effect, possibly overestimating the cognitive impact of the intervention. Second, the diagnosis of MCI relied solely on clinical assessment tools. Future studies on the effect of αGPC on MCI patient subgrouping patients based on the presence of amyloid plaque will offer a more direct insight into how αGPC affects AD pathology. Studies with longer durations using biomarkers are needed for a more comprehensive understanding of the effect of αGPC on individuals with MCI and the progression to AD. Despite these limitations, our findings suggest the efficacy and safety of αGPC for individuals with aMCI. αGPC is a potential cost-effective therapeutic option for MCI. The results of our study demonstrate the efficacy and safety of αGPC for MCI. Over a 12-week period, αGPC treatment led to a notable decrease in the ADAS-cog score by 2.34 points. Furthermore, there were no noticeable differences in side effects or tolerability when compared to the placebo group. These findings highlight αGPC as a promising therapeutic option for MCI. Abbreviations αGPC alpha glyceryl phosphorylcholine MCI mild cognitive impairment aMCI amnestic mild cognitive impairment AD Alzheimer’s disease ADAS Alzheimer’s Disease Assessment Scale ADAS-cog Alzheimer’s Disease Assessment Scale–cognitive subscale ADAS-noncog Alzheimer’s Disease Assessment Scale–non-cognitive subscale AEs adverse effects RCT randomized control trial SVLT Seoul Verbal Learning Test MoCA-K Korean version of the Montreal Cognitive Assessment Visual C.P.T Visual Continuous Performance Test K-CWST Korean-Color Word Stroop Test S-IADL Seoul-Instrumental Activities of Daily Living SCD-Q Subjective Cognitive Decline Questionnaire SGDS-K Korean version of the Short Form Geriatric Depression Scale ITT intention-to-treat Declarations Ethics approval and consent to participate. This study was approved by Institutional Review Board of the conducting institutions (Yongin Severance Hospital; 9-2021-0085, Myongji Hospital; 2021-07-035). Informed consent to participate was obtained from all the participants. All methods were carried out in accordance with declaration of Helsinki. Consent for publication Not applicable. Availability of data and materials The data used and analysed in this study are available from the corresponding author on reasonable request. Competing interests The authors declare no competing interests. Funding This research was supported by the Suheung, Osong-eup, Cheongju-si, Chungcheongbuk-do, Republic of Korea; and the HSBio, Jincheon-gun, Chungcheongbuk-do, Republic of Korea; and the Pharmirae Co. Ltd., Seongnam-si, Gyeonggi-do, Republic of Korea. Authors' contributions Study concept and design: JG, WJ. KD. Data management: KD, JG, WJ. Intervention: JG, WJ, SY, CW, SH Statistical analysis: JW, SY, SJ Analysis and interpretation of data: JW, SJ, WJ. Writing Original draft: JW, JG. All authors read and approved the final manuscript. Acknowledgements We want to thank to Sung Hyun Cho, a professional clinical psychologist, for his essential contribution in conducting various neuropsychiatric test throughout the study. References Organization WH. Global status report on the public health response to dementia. 2021. Huey ED, Manly JJ, Tang M-X, Schupf N, Brickman AM, Manoochehri M, et al. Course and etiology of dysexecutive MCI in a community sample. Alzheimer's & Dementia. 2013;9(6):632-9. Petersen RC. Mild cognitive impairment as a diagnostic entity. Journal of internal medicine. 2004;256(3):183-94. Fischer P, Jungwirth S, Zehetmayer S, Weissgram S, Hoenigschnabl S, Gelpi E, et al. Conversion from subtypes of mild cognitive impairment to Alzheimer dementia. Neurology. 2007;68(4):288-91. Matthews FE, Stephan BC, McKeith IG, Bond J, Brayne C, Function MRCC, et al. Two‐year progression from mild cognitive impairment to dementia: to what extent do different definitions agree? Journal of the American Geriatrics Society. 2008;56(8):1424-33. Petersen RC, Lopez O, Armstrong MJ, Getchius TS, Ganguli M, Gloss D, et al. Practice guideline update summary: Mild cognitive impairment: Report of the Guideline Development, Dissemination, and Implementation Subcommittee of the American Academy of Neurology. Neurology. 2018;90(3):126-35. Asaoka D, Xiao J, Takeda T, Yanagisawa N, Yamazaki T, Matsubara Y, et al. Effect of probiotic Bifidobacterium breve in improving cognitive function and preventing brain atrophy in older patients with suspected mild cognitive impairment: results of a 24-week randomized, double-blind, placebo-controlled trial. Journal of Alzheimer's Disease. 2022;88(1):75-95. Alavi Naeini A, Elmadfa I, Djazayery A, Barekatain M, Aghaye Ghazvini M, Djalali M, et al. The effect of antioxidant vitamins E and C on cognitive performance of the elderly with mild cognitive impairment in Isfahan, Iran: a double-blind, randomized, placebo-controlled trial. European journal of nutrition. 2014;53:1255-62. Doody R, Ferris S, Salloway S, Sun Y, Goldman R, Watkins W, et al. Donepezil treatment of patients with MCI: a 48-week randomized, placebo-controlled trial. Neurology. 2009;72(18):1555-61. Petersen RC, Thomas RG, Grundman M, Bennett D, Doody R, Ferris S, et al. Vitamin E and donepezil for the treatment of mild cognitive impairment. N Engl J Med. 2005;352(23):2379-88. Zeisel SH. Nutritional importance of choline for brain development. Journal of the American College of Nutrition. 2004;23(sup6):621S-6S. Parnetti L, Amenta F, Gallai V. Choline alphoscerate in cognitive decline and in acute cerebrovascular disease: an analysis of published clinical data. Mech Ageing Dev. 2001;122(16):2041-55. Barbagallo Sangiorgi G, Barbagallo M, Giordano M, Meli M, Panzarasa R. alpha-Glycerophosphocholine in the mental recovery of cerebral ischemic attacks. An Italian multicenter clinical trial. Ann N Y Acad Sci. 1994;717:253-69. Perri RD, Coppola G, Ambrosio L, Grasso A, Puca F, Rizzo M. A multicentre trial to evaluate the efficacy and tolerability of α-glycerylphosphorylcholine versus cytosine diphosphocholine in patients with vascular dementia. Journal of international medical research. 1991;19(4):330-41. De Jesus Moreno Moreno M. Cognitive improvement in mild to moderate Alzheimer's dementia after treatment with the acetylcholine precursor choline alfoscerate: a multicenter, double-blind, randomized, placebo-controlled trial. Clin Ther. 2003;25(1):178-93. Soininen H, Solomon A, Visser PJ, Hendrix SB, Blennow K, Kivipelto M, et al. 24-month intervention with a specific multinutrient in people with prodromal Alzheimer's disease (LipiDiDiet): a randomised, double-blind, controlled trial. The Lancet Neurology. 2017;16(12):965-75. Doraiswamy P, Bieber F, Kaiser L, Krishnan K, Reuning-Scherer J, Gulanski B. The Alzheimer's Disease Assessment Scale: patterns and predictors of baseline cognitive performance in multicenter Alzheimer's disease trials. Neurology. 1997;48(6):1511-7. Youn J, Lee D, Kim K, Lee J, Jhoo J, Lee K, et al. Development of the Korean version of Alzheimer's disease assessment scale (ADAS‐K). International journal of geriatric psychiatry. 2002;17(9):797-803. Kang Y, Park J, Yu K, Lee B, editors. The validity of the Korean-Montreal Cognitive Assessment (K-MoCA) as a screening test for both MCI and VCI. Front Hum Neurosci Conference Abstract: The 20th Annual Rotman Research Institute Conference, The Frontal Lobes; 2010. Riccio CA, Reynolds CR, Lowe P, Moore JJ. The continuous performance test: a window on the neural substrates for attention? Archives of clinical neuropsychology. 2002;17(3):235-72. Kim TY, Kim S, Sohn JE, Lee EA, Yoo BG, Lee SC, et al. Development of the Korean Stroop Test and Study of the Validity and the Reliability. Journal of the Korean Geriatrics Society. 2004;8(4):233-40. KU H-M, KIM J-H, KWON E-J, KIM S-H, LEE H-S, KO H-J, et al. A study on the reliability and validity of Seoul-Instrumental Activities of Daily Living (S-IADL). Journal of Korean Neuropsychiatric Association. 2004:189-99. Rami L, Mollica MA, García-Sanchez C, Saldaña J, Sanchez B, Sala I, et al. The subjective cognitive decline questionnaire (SCD-Q): a validation study. Journal of Alzheimer's Disease. 2014;41(2):453-66. LEE S-C, KIM W-H, CHANG S-M, KIM B-S, LEE D-W, BAE J-N, et al. The use of the Korean version of Short Form Geriatric Depression Scale (SGDS-K) in the community dwelling elderly in Korea. Journal of Korean Geriatric Psychiatry. 2013:37-43. Suzuki T, Shimada H, Makizako H, Doi T, Yoshida D, Ito K, et al. A randomized controlled trial of multicomponent exercise in older adults with mild cognitive impairment. PloS one. 2013;8(4):e61483. Spiers PA, Myers D, Hochanadel GS, Lieberman HR, Wurtman RJ. Citicoline improves verbal memory in aging. Archives of neurology. 1996;53(5):441-8. Na G, Kwak SH, Jang SH, Noh HE, Kim J, Yang S, et al. Supplementary effect of choline alfoscerate on speech recognition in patients with age-related hearing loss: A prospective study in 34 patients (57 ears). Frontiers in Aging Neuroscience. 2021;13:684519. Traini E, Bramanti V, Amenta F. Choline alphoscerate (alpha-glyceryl-phosphoryl-choline) an old choline-containing phospholipid with a still interesting profile as cognition enhancing agent. Current Alzheimer Research. 2013;10(10):1070-9. Li Q, Li X, Wang J, Liu H, Kwong JS-W, Chen H, et al. Diagnosis and treatment for hyperuricemia and gout: a systematic review of clinical practice guidelines and consensus statements. BMJ open. 2019;9(8):e026677. Lee G, Choi S, Chang J, Choi D, Son JS, Kim K, et al. Association of L-α glycerylphosphorylcholine with subsequent stroke risk after 10 years. JAMA network open. 2021;4(11):e2136008-e. Additional Declarations No competing interests reported. Supplementary Files SupplementaryTable1CAMCIRCT.docx SupplementaryTable2CAMCIRCT.docx supplementaryTable3CAMCIRCT.docx Cite Share Download PDF Status: Published Journal Publication published 19 Sep, 2024 Read the published version in BMC Geriatrics → Version 1 posted Editorial decision: Revision requested 31 May, 2024 Reviews received at journal 18 May, 2024 Reviewers agreed at journal 26 Apr, 2024 Reviews received at journal 26 Mar, 2024 Reviewers agreed at journal 15 Mar, 2024 Reviewers invited by journal 13 Mar, 2024 Editor assigned by journal 07 Feb, 2024 Editor invited by journal 31 Oct, 2023 Submission checks completed at journal 31 Oct, 2023 First submitted to journal 24 Oct, 2023 You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-3488308","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Research Article","associatedPublications":[],"authors":[{"id":244390770,"identity":"e49fcaf7-5d39-44a7-be9f-6b114fdb4c41","order_by":0,"name":"Jong-Wook Jeon","email":"","orcid":"","institution":"Myongji Hospital","correspondingAuthor":false,"submittingAuthor":false,"prefix":"","firstName":"Jong-Wook","middleName":"","lastName":"Jeon","suffix":""},{"id":244390771,"identity":"bebba6da-27d8-429b-aa07-42e18db7c22b","order_by":1,"name":"Su-Young Lee","email":"","orcid":"","institution":"Myongji 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Kim","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAA0ElEQVRIiWNgGAWjYJACAxBmY2A+wMDYQJoWtgTitUC18RgQp8XgePOBYt4dtcZ8Yme+SfPuqGPgbz9AQMuZYwnGvGeOm7FJ526T5j1zmEHiTAJ+LWY3cgyMeduO2UC0tAFtuEHAYUhacp4BtdQxyBOppQbosBw2oBZmBgNCWuyBfjGc23bAmE06zdhybtthHkNCfpFsbz5m8LatznD+7OSHN4AMObnjBwhYw8DABoyTwyAGiwSQ4CGoHgiYHzAw1IEZH4hRPgpGwSgYBSMPAACL2T/xX3QZYwAAAABJRU5ErkJggg==","orcid":"","institution":"Yongin Severance Hospital","correspondingAuthor":true,"submittingAuthor":false,"prefix":"","firstName":"Woo","middleName":"Jung","lastName":"Kim","suffix":""}],"badges":[],"createdAt":"2023-10-25 02:44:22","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-3488308/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-3488308/v1","draftVersion":[],"editorialEvents":[{"content":"https://doi.org/10.1186/s12877-024-05366-7","type":"published","date":"2024-09-19T15:56:59+00:00"}],"editorialNote":"","failedWorkflow":false,"files":[{"id":45686890,"identity":"1116b818-5461-48e7-a30f-824130fc22f8","added_by":"auto","created_at":"2023-11-01 20:46:45","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":63586,"visible":true,"origin":"","legend":"\u003cp\u003eThe CONSORT flowchart\u003c/p\u003e\n\u003cp\u003e\u003cem\u003eαGPC\u003c/em\u003e Choline alphoscerate\u003c/p\u003e","description":"","filename":"figure1CAMCIRCT.png","url":"https://assets-eu.researchsquare.com/files/rs-3488308/v1/edb2b9999939e62014b8b688.png"},{"id":45686892,"identity":"62ed033b-41e7-4073-8b89-4db54e98adcf","added_by":"auto","created_at":"2023-11-01 20:46:45","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":509731,"visible":true,"origin":"","legend":"\u003cp\u003eResults of the tests showing significant differences between the αGPC group and placebo group\u003c/p\u003e\n\u003cp\u003e\u003cem\u003eαGPC\u003c/em\u003e Choline alphoscerate\u003c/p\u003e","description":"","filename":"figure2CAMCIRCT.png","url":"https://assets-eu.researchsquare.com/files/rs-3488308/v1/ed7ed99bf39a3c1fe99bdb9b.png"},{"id":65104099,"identity":"b403787e-e72e-4d62-87d0-27c93e078566","added_by":"auto","created_at":"2024-09-23 16:11:38","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":1561906,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-3488308/v1/025c8b7f-a78c-4b59-ad26-981a251dbc9d.pdf"},{"id":45686891,"identity":"49a8d67a-c82f-40d4-bf30-881df1480426","added_by":"auto","created_at":"2023-11-01 20:46:45","extension":"docx","order_by":1,"title":"","display":"","copyAsset":false,"role":"supplement","size":15363,"visible":true,"origin":"","legend":"","description":"","filename":"SupplementaryTable1CAMCIRCT.docx","url":"https://assets-eu.researchsquare.com/files/rs-3488308/v1/ee6462fc372ec4c932e98fbe.docx"},{"id":45686893,"identity":"cd73a30a-8e2d-4090-88f1-084da211e316","added_by":"auto","created_at":"2023-11-01 20:46:45","extension":"docx","order_by":2,"title":"","display":"","copyAsset":false,"role":"supplement","size":16493,"visible":true,"origin":"","legend":"","description":"","filename":"SupplementaryTable2CAMCIRCT.docx","url":"https://assets-eu.researchsquare.com/files/rs-3488308/v1/6523abd1216ce65e237592e1.docx"},{"id":45686894,"identity":"263b5655-97f0-46a2-bf06-3404084c8fdd","added_by":"auto","created_at":"2023-11-01 20:46:45","extension":"docx","order_by":3,"title":"","display":"","copyAsset":false,"role":"supplement","size":26900,"visible":true,"origin":"","legend":"","description":"","filename":"supplementaryTable3CAMCIRCT.docx","url":"https://assets-eu.researchsquare.com/files/rs-3488308/v1/8bcf4d53ad5551346e884371.docx"}],"financialInterests":"No competing interests reported.","formattedTitle":"Efficacy and Safety of Choline Alphoscerate for Amnestic Mild Cognitive Impairment: A Randomized Double-Blind Placebo-Controlled Trial","fulltext":[{"header":"1. Background","content":"\u003cp\u003eDementia is a major global health challenge that imposes substantial societal burdens and costs. According to a report by the World Health Organization in 2021 [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e], the number of people living with dementia was estimated to be approximately 50\u0026nbsp;million and is anticipated to triple by 2050. Mild cognitive impairment (MCI) is considered a transitional state between normal cognitive aging and dementia [\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e, \u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e]. MCI is characterized by a noticeable cognitive decline with limited disruption of instrumental activities of daily living but does not meet the criteria for dementia [\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e]. In particular, amnestic MCI (aMCI), which features prominent memory impairment, has a higher rate of progression to Alzheimer\u0026rsquo;s disease (AD) dementia [\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e]. The progression rate from MCI to dementia over a short time is 20\u0026ndash;40%, with longer-term progression spanning 60\u0026ndash;100% over 5\u0026ndash;10 years [\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e, \u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e]. Identifying effective interventions for MCI is important to delay or prevent dementia and improve the quality of life of affected individuals.\u003c/p\u003e \u003cp\u003eNumerous pharmacological choices, such as cholinesterase inhibitors and dietary supplements, along with non-pharmacological interventions, such as exercise and cognitive training, have been proposed as potential treatments for MCI [\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e, \u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e, \u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e]. However, clinical trials have yielded inconsistent outcomes, often showing minimal or negligible effects. With respect to cholinesterase inhibitors, the treatment of choice for AD dementia, a previous study demonstrated cognitive improvement of approximately a 1.0-point decrease in the Alzheimer\u0026rsquo;s Disease Assessment Scale\u0026ndash;cognitive subscale (ADAS-cog) score in patients with MCI. However, adverse effects (AEs) in the treatment group were more than double that in the placebo group, and compliance was low (55% of participants who received donepezil) [\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e]. In a large-scale randomized control trial (RCT), where the primary outcome measure was the progression rate to AD, no significant difference was observed between the donepezil group and the placebo group, although AEs were significantly more prevalent in the donepezil group [\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e]. Because of these reason, regular exercise is the only recommended management option for patients with MCI according to the practical guidelines of the American Academy of Neurology [\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eCholine alphoscerate (alpha-glyceryl-phosphorylcholine, αGPC) is a choline-containing phospholipid that is often used as a dietary supplement. Choline passes through the blood-brain barrier, which results in increased choline levels. Choline is a precursor of acetylcholine, an essential neurotransmitter for memory and learning. In animal experiments, choline plays a pivotal role in brain development, particularly in hippocampal maturation [\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e]. Previous clinical studies have shown that αGPC is effective in managing cognitive decline of vascular origin and in AD dementia [\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e, \u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e, \u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e, \u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e]. Further, clinical evidence suggests that choline-enriched multi-nutrient dietary intervention may have a beneficial impact in managing MCI due to AD [\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e]. These studies suggest that αGPC may be an effective management intervention for MCI.\u003c/p\u003e \u003cp\u003eTherefore, it is important to conduct clinical trials to examine the effects of αGPC on MCI and determine its potential as a viable treatment option. To this end, we conducted a 12-week multicenter, randomized, double-blind, placebo-controlled trial.\u003c/p\u003e"},{"header":"2. Methods","content":"\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e \u003ch2\u003e2.1 Settings\u003c/h2\u003e \u003cp\u003eThis 12-week, multicenter, randomized, double-blind, placebo-controlled, parallel-group trial was conducted at two hospital sites in the Republic of Korea. The study protocol (versionV1.0, June 24th, 2021) complied with the Declaration of Helsinki and was approved by the Institutional Review Board of the conducting institutions (Yongin Severance Hospital; 9-2021-0085, Myongji Hospital; 2021-07-035). The study is registered in the Clinical Research Information Service. Osong (Chungcheongbuk-do): Korea Centers for Disease Control and Prevention, Ministry of Health and Welfare (Republic of Korea); 2010; 14/09/2023; KCT0008797; A 12-week, multicenter, randomized, double-blind, placebo-controlled human application study to evaluate the efficacy and safety of SHCog\u0026trade; on cognitive function improvement in mild cognitive decline.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec4\" class=\"Section2\"\u003e \u003ch2\u003e2.2 Study Subject\u003c/h2\u003e \u003cp\u003eOne hundred study subjects were recruited through advertisements. Overall healthy subjects who experienced cognitive decline were tested for aMCI by a certified clinician using neurocognitive tests. Exclusion of dementia were carried out through evaluation by psychiatrists. The inclusion criteria were participants aged between 55 and 85 years old and a decline of 1.0 standard deviation or more in either memory scores (Word List Memory of Word List Recall or Word List Recognition) on the Korean version of the neuropsychological assessment developed by the Consortium to Establish a Registry for Alzheimer\u0026rsquo;s Disease, or on the Seoul Verbal Learning Test (SVLT) of the Seoul neuropsychological screening battery.\u003c/p\u003e \u003cp\u003eThe exclusion criteria were as follows: 1) patients with concurrent neurodegenerative conditions, such as AD or Parkinson's disease; 2) current mental disorders (e.g., major depressive disorder, schizophrenia, alcohol use disorder)according to DSM-5 criteria; 3) patients who had taken medications known to affect cognitive function within 4 weeks before the initial visit (all types of psychotropics including antidepressants, nootropics, supplements for brain function) 4) ongoing treatment for severe immune, respiratory, gastrointestinal/hepatic/biliary, renal/urinary, neurological, musculoskeletal, and infectious diseases or malignancies; 5) a history of head trauma with loss of consciousness within 6 months before the initial visit; 6) a history of cardiovascular disease within 6 months before the initial visit; 7) vitamin E supplementation exceeding 400 IU per day or anticipated inability to reduce the dosage; 8) use of estrogen replacement therapy (excluding local applications) within 2 months before the initial visit; 9) use of dietary supplement related to cognitive improvement within 2 months before the initial visit; 10) thyroid disease with thyroid-stimulating hormone (TSH) levels below 0.1 \u0026micro;IU/mL or above 10 \u0026micro;IU/mL; 11) creatinine levels exceeding twice the normal upper limit; 12) aspartate transaminase (AST) or alanine aminotransferase (ALT) levels exceeding three times the normal upper limit; 13) uncontrolled hypertension and diabetes; 14) sensitivity or allergy to the ingredients of the investigational product; 15) pregnancy, breastfeeding, or planning to get pregnant during the study period; 16) participation in any other interventional clinical trial (including clinical trials other than the current study) within 3 months before the initial visit, or planned participation in any other clinical trial (including clinical trials other than the current study) after the start of the current study. All enrolled subjects were provided written informed consent after receiving a complete description of the study protocol.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec5\" class=\"Section2\"\u003e \u003ch2\u003e2.3 Randomization and blinding\u003c/h2\u003e \u003cp\u003eA block randomization method was used for randomization. To ensure balanced randomization between the αGPC group and the placebo group, the ratio of participants in each group was set to 1:1. The randomization table was generated using the SAS software randomization program, which applied a permutation of random numbers to the sequential test subject numbers, starting from number one. Drug labeling was performed according to the randomization table, and the labeled drugs were supplied to the institutions before the start of the trial.\u003c/p\u003e \u003cp\u003eTo maintain blinding, the assignment details (information about blinding) for each group were securely managed by the trial coordinator. Except in cases where it was necessary because of significant adverse drug reactions, the blinding codes were not disclosed until the end of the trial. The investigators administered the randomly assigned drug corresponding to the allocated blinding code to the eligible participants during the treatment phase human application phase of the trial. To maintain blinding, reserves (specific to each unique code) were used in cases of shortage or damage to the drugs. Throughout the study, there were no occurrences of unblinding during the trial period.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec6\" class=\"Section2\"\u003e \u003ch2\u003e2.4 Raw Material\u003c/h2\u003e \u003cp\u003eSHCog\u0026trade; is a branded α-GPC (HS Bio, Republic of Korea), prepared from Soybean lecithin and is highly viscose, as it absorbs moisture up to 14\u0026thinsp;~\u0026thinsp;18.5%. Materials used for the manufacturing process and residual solvent standards comply with food regulations of Korea. The raw materials were stored at room temperature until test product is prepared as a soft capsule format.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec7\" class=\"Section2\"\u003e \u003ch2\u003e2.5 Interventions\u003c/h2\u003e \u003cp\u003eEnrolled subjects were administered αGPC or placebo once daily with adequate water for a duration of 12 weeks. Based on the choline dosage recommended by the National Academies Press, and considering previous studies, a single dose of the drug was determined to contain 727 mg of SHCog\u0026trade;, which is equivalent to 600 mg of aGPC (HSBio, Republic of Korea). Enrolled subjects were allowed to continue taking medications and dietary supplements that were deemed unlikely to affect the interpretation of the results. However, the following medications were prohibited during the trial because of their potential to influence the interpretation of the results: 1) medications that affect cognitive function (e.g., antipsychotics, tricyclic antidepressant, neurodegenerative disease drugs, nootropics) 2) vitamin E supplementation exceeding 400 IU per day, 3) estrogen replacement therapy (excluding local applications), and 4) dietary supplements associated with cognitive improvement.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec8\" class=\"Section2\"\u003e \u003ch2\u003e2.6 Outcome assessments\u003c/h2\u003e \u003cp\u003eThe primary outcome was a change in the total score Alzheimer\u0026rsquo;s Disease Assessment Scale\u0026ndash;cognitive subscale (ADAS-cog score). The Alzheimer Disease Assessment Scale (ADAS) consists of cognitive and noncognitive sections. ADAS-Cog, which is cognitive section of ADAS, aims to assess various cognitive domains in dementia patients, including memory, language abilities, and executive function, among others [\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e, \u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e]. We additionally assess concentration abilities through an item in noncognitive section. The secondary outcome assessment included the Korean version of the Montreal Cognitive Assessment (MoCA-K) [\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e], the Visual Continuous Performance Test (Visual C.P.T) [\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e], the Korean-Color Word Stroop Test (K-CWST) [\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e], Seoul-Instrumental Activities of Daily Living (S-IADL) [\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e], Subjective Cognitive Decline Questionnaire (SCD-Q) [\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e], and the Korean version of the Short Form Geriatric Depression Scale (SGDS-K) [\u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e]. These outcomes were assessed at baseline and 12 weeks after baseline.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec9\" class=\"Section2\"\u003e \u003ch2\u003e2.7 Safety assessment\u003c/h2\u003e \u003cp\u003eSafety assessments included monitoring of AEs, clinical laboratory tests (hematological/blood chemistry and urinalysis), vital signs (blood pressure and pulse rate), and physical measurements (body weight). These assessments were conducted at screening (2 weeks before baseline), baseline, 6 weeks after baseline, and 12 weeks after baseline.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec10\" class=\"Section2\"\u003e \u003ch2\u003e2.8 Sample size and power analysis\u003c/h2\u003e \u003cp\u003eA sample size of 35 per treatment group was estimated to assess the effectiveness of αGPC, compared with that of placebo, using primary efficacy variables (ADAS-cog score), with 80% power at a significance level of 0.05. To account for a potential dropout rate of 30%, we enrolled 50 participants in each group, resulting in a total enrollment of 100 individuals across both treatment groups.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec11\" class=\"Section2\"\u003e \u003ch2\u003e2.9 Statistical Analysis\u003c/h2\u003e \u003cp\u003eOutcome analysis was carried out based on an intention-to-treat (ITT) dataset, defined as the subset of participants who received at least one dose of medication after randomization. The statistical analysis was conducted using SAS\u0026reg; software (Version 9.4, SAS Institute, Cary, North Carolina, USA).\u003c/p\u003e \u003cp\u003eTo evaluate efficacy variables, including the ADAS-cog score, MoCA-K, visual C.P.T, K-CWST, S-IADL, SCD-Q, and SGDS-K, intra-group comparisons of pre- and post-intake changes were performed using paired t-test. The difference in extent of changes between the αGPC group and the placebo group at each time point was assessed using two sample t-test or Wilcoxon rank-sum test. Demographics and results of biological tests (Laboratory examination, measuring vital signs and body weight) were analyzed using a two-sample t-test or the Wilcoxon rank-sum test. Chi-square or Fisher's exact test was used to analyze categorical data.\u003c/p\u003e \u003c/div\u003e"},{"header":"3. Results","content":"\u003cdiv id=\"Sec13\" class=\"Section2\"\u003e \u003ch2\u003e3.1. Baseline characteristics\u003c/h2\u003e \u003cp\u003eOne hundred subjects were enrolled in this study, of whom 52 received αGPC and 48 received placebo (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e). All 100 subjects were included in the ITT population, whereas 74 subjects (74%) were included in the per-protocol population. For the primary and secondary outcomes, 42 subjects in the αGPC group and 32 subjects in the placebo group were analyzed.\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003eTable\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e summarizes baseline characteristics of study participants. The αGPC and placebo groups showed similar distributions in terms of sex, age, education level, smoking and alcohol status, exercise habits, and stress severity. The results of all neuropsychiatric tests are presented in Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e.\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab1\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eBaseline demographic and clinical characteristics of the participants.\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"5\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colspan=\"2\" morerows=\"1\" nameend=\"c2\" namest=\"c1\" rowspan=\"2\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eαGPC (N\u0026thinsp;=\u0026thinsp;42)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003ePlacebo (N\u0026thinsp;=\u0026thinsp;32)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003e\u003cem\u003eP\u003c/em\u003e-value\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eMean (SD) or N (%)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eMean (SD) or N (%)\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e \u003cp\u003e\u003cb\u003eSex\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eMale\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e12 (28.57)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e8 (25.00)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003e0.732\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eFemale\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e30 (71.43)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e24 (75.00)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e \u003cp\u003e\u003cb\u003eAge (years)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e70.52 (9.05)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e71.75 (8.43)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e50\u0026ndash;59\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e7 (16.67)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e4 (12.50)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\" morerows=\"3\" rowspan=\"4\"\u003e \u003cp\u003e0.555\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e60\u0026ndash;69\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e11 (26.19)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e8 (25.00)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e70\u0026ndash;79\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e16 (38.10)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e15 (46.88)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e\u0026ge;\u0026thinsp;80\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e8 (19.05)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e5 (15.63)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e \u003cp\u003e\u003cb\u003eEducation level\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eNo education\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e3 (7.14)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e3 (9.38)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\" morerows=\"5\" rowspan=\"6\"\u003e \u003cp\u003e0.866\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eElementary school graduate\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e10 (23.81)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e6 (18.75)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eMiddle school graduate\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e6 (14.29)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e3 (9.38)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eHigh school graduate\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e18 (42.86)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e13 (40.63)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eCollege or University graduate\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e4 (9.52)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e5 (15.63)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eUniversity postgraduate\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e1 (2.38)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e2 (6.25)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e \u003cp\u003e\u003cb\u003eSmoking status\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eNever smoker\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e34 (80.95)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e28 (87.50)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\" morerows=\"3\" rowspan=\"4\"\u003e \u003cp\u003e0.513\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eQuit (\u0026ge;\u0026thinsp;1 year)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e6 (14.29)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e2 (6.25)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eQuit (\u0026lt;\u0026thinsp;1 year)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e1 (2.38)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e0 (0.00)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eCurrent smoker\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e1 (2.38)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e2 (6.25)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e \u003cp\u003e\u003cb\u003eAlcohol intake\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e34 (80.95)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e25 (78.13)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\" morerows=\"1\" rowspan=\"2\"\u003e \u003cp\u003e0.764\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eYes\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e8 (19.05)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e7 (21.88)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e \u003cp\u003e\u003cb\u003eExercise\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eNo\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e10 (23.81)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e1 (3.13)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\" morerows=\"4\" rowspan=\"5\"\u003e \u003cp\u003e0.118\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e1\u0026ndash;2 times/week\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e6 (14.29)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e8 (25.00)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e3\u0026ndash;4 times/week\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e10 (23.81)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e9 (28.13)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003e5\u0026ndash;6 times/week\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e9 (21.43)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e10 (31.25)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eDaily\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e7 (16.67)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e4 (12.50)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"2\" nameend=\"c2\" namest=\"c1\"\u003e \u003cp\u003e\u003cb\u003eStress severity\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e\u0026nbsp;\u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eNone\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e4 (9.52)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e6 (18.75)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\" morerows=\"3\" rowspan=\"4\"\u003e \u003cp\u003e0.501\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eMild\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e29 (69.05)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e20 (62.50)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eModerate\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e8 (19.05)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e4 (12.50)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eSevere\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c3\"\u003e \u003cp\u003e1 (2.38)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"char\" char=\".\" colname=\"c4\"\u003e \u003cp\u003e2 (6.25)\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"5\"\u003e\u003cem\u003eαGPC\u003c/em\u003e Choline alphoscerate\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab2\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 2\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eMajor results of neuropsychiatric tests before and after 12 weeks of choline alphoscerate (αGPC) and placebo administration\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"9\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c7\" colnum=\"7\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c8\" colnum=\"8\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c9\" colnum=\"9\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colspan=\"2\" morerows=\"2\" nameend=\"c2\" namest=\"c1\" rowspan=\"3\"\u003e\u0026nbsp;\u003c/th\u003e \u003cth align=\"left\" colspan=\"3\" nameend=\"c5\" namest=\"c3\"\u003e \u003cp\u003eαGPC group (N\u0026thinsp;=\u0026thinsp;42)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colspan=\"3\" nameend=\"c8\" namest=\"c6\"\u003e \u003cp\u003ePlacebo group (N\u0026thinsp;=\u0026thinsp;32)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c9\" morerows=\"2\" rowspan=\"3\"\u003e \u003cp\u003eP-value\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003ctr\u003e \u003cth align=\"left\" colspan=\"3\" nameend=\"c5\" namest=\"c3\"\u003e \u003cp\u003eMean (SD)\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colspan=\"3\" nameend=\"c8\" namest=\"c6\"\u003e \u003cp\u003eMean (SD)\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eBaseline\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c4\"\u003e \u003cp\u003eWeek 12\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c5\"\u003e \u003cp\u003eChange\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c6\"\u003e \u003cp\u003eBaseline\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c7\"\u003e \u003cp\u003eWeek 12\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c8\"\u003e \u003cp\u003eChange\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"9\" nameend=\"c9\" namest=\"c1\"\u003e \u003cp\u003e\u003cb\u003eADAS-cog\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eTotal score\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e10.40 (4.33)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e8.06 (4.28)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u003cb\u003e-2.34 (3.26)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e9.14 (3.33)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e8.17 (3.00)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e\u003cb\u003e-0.97 (2.32)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e\u003cb\u003e0.048\u003c/b\u003e\u003csup\u003e\u003cb\u003e\u0026Dagger;\u003c/b\u003e\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eMemory domain\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e7.79 (3.43)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e6.04 (3.64)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u003cb\u003e-1.75 (2.63)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e6.67 (2.20)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e6.01 (2.25)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e\u003cb\u003e-0.66 (1.67)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e\u003cb\u003e0.034\u003c/b\u003e\u003csup\u003e\u0026Dagger;\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eTotal score\u0026thinsp;+\u0026thinsp;concentration domain of ADAS-noncog\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e10.45 (4.30)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e8.06 (4.28)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u003cb\u003e-2.39 (3.25)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e9.20 (3.39)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e8.26 (2.98)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e\u003cb\u003e-0.94 (2.37)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e\u003cb\u003e0.037\u003c/b\u003e\u003csup\u003e\u0026Dagger;\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"9\" nameend=\"c9\" namest=\"c1\"\u003e \u003cp\u003e\u003cb\u003eMoCA-K\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eTotal score\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e21.24 (3.74)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e22.95 (4.23)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u003cb\u003e1.71 (2.65)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e21.88 (3.75)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e22.25 (4.39)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e0.38 (2.61)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e0.105\u003csup\u003e\u0026sect;\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eVisuospatial/Executive\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e3.98 (1.14)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e4.21 (0.92)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.24 (1.03)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e4.00 (1.05)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e4.09 (0.96)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e0.09 (0.89)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e0.716\u003csup\u003e\u0026sect;\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eAttention\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e4.71 (1.35)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e5.00 (1.15)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.29 (1.27)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e5.25 (0.92)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e4.94 (1.22)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e-0.31 (1.35)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e0.074\u003csup\u003e\u0026sect;\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eLanguage\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e2.33 (0.82)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e2.45 (0.59)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.12 (0.74)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e2.19 (0.82)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e2.31 (0.78)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e0.13 (0.77)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e0.882\u003csup\u003e\u0026sect;\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eAbstraction\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e1.00 (0.77)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1.10 (0.82)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.10 (0.62)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.97 (0.82)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0.81 (0.78)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e-0.16 (0.77)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e0.102\u003csup\u003e\u0026sect;\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eDelayed recall\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.86 (0.95)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1.64 (1.65)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u003cb\u003e0.79 (1.41)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e1.00 (1.41)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e1.81 (1.73)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e\u003cb\u003e0.81 (1.42)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e0.844\u003csup\u003e\u0026sect;\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eOrientation\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e5.74 (0.54)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e5.71 (0.83)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e-0.02 (0.64)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e5.75 (0.62)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e5.66 (0.83)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e-0.09 (0.59)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e0.585\u003csup\u003e\u0026sect;\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eNaming\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e2.38 (0.94)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e2.60 (0.77)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u003cb\u003e0.21 (0.42)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e2.56 (0.76)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e2.47 (0.80)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e-0.09 (0.39)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e\u003cb\u003e0.003\u003c/b\u003e\u003csup\u003e\u0026sect;\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colspan=\"9\" nameend=\"c9\" namest=\"c1\"\u003e \u003cp\u003e\u003cb\u003eK-CWST\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eTime of word naming (s)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e15.35 (3.72)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e14.16 (2.79)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e\u003cb\u003e-1.19 (3.10)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e15.21 (5.42)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e13.55 (3.20)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e\u003cb\u003e-1.66 (3.58)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e0.548\u003csup\u003e\u0026sect;\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eTime of color naming (s)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e27.64 (12.22)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e26.19 (11.99)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e-1.45 (9.18)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e24.57 (12.80)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e24.30 (9.49)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e-0.27 (6.19)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e\u003cb\u003e0.048\u003c/b\u003e\u003csup\u003e\u0026sect;\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eTime of congruent word naming (s)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e15.33 (3.76)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e14.93 (4.23)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e-0.41 (3.34)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e14.96 (5.09)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e14.20 (4.42)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e-0.76 (3.64)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e0.832\u003csup\u003e\u0026sect;\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eTime of incongruent word naming (s)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e20.72 (12.43)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e20.17 (13.09)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e-0.55 (7.16)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e17.43 (8.75)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e17.40 (7.89)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e-0.03 (5.77)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e0.635\u003csup\u003e\u0026sect;\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eTime of incongruent color naming (s)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e72.26 (45.20)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e65.90 (47.57)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e-6.36 (24.36)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e60.09 (31.07)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e56.37 (30.15)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e-3.73 (13.47)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e0.604\u003csup\u003e\u0026sect;\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eError of word naming (n)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.60 (3.70)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.00 (0.00)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e-0.60 (3.70)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.00 (0.00)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0.03 (0.18)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e0.03 (0.18)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e0.100\u003csup\u003e\u0026sect;\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eError of color naming (n)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.86 (1.84)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.67 (1.96)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e-0.19 (1.52)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.59 (1.27)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0.47 (0.88)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e-0.13 (0.87)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e0.879\u003csup\u003e\u0026sect;\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eError of congruent word naming (n)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.05 (0.22)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.07 (0.34)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.02 (0.41)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.16 (0.72)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0.06 (0.25)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e-0.09 (0.78)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e0.976\u003csup\u003e\u0026sect;\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eError of incongruent word naming (n)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e0.19 (0.59)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e0.19 (0.63)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e0.00 (0.66)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e0.16 (0.57)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0.19 (0.47)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e0.03 (0.47)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e0.603\u003csup\u003e\u0026sect;\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eError of incongruent color naming (n)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003e2.29 (3.13)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c4\"\u003e \u003cp\u003e1.79 (2.68)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c5\"\u003e \u003cp\u003e-0.50 (1.67)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c6\"\u003e \u003cp\u003e1.03 (1.64)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c7\"\u003e \u003cp\u003e0.59 (1.04)\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c8\"\u003e \u003cp\u003e\u003cb\u003e-0.44 (1.01)\u003c/b\u003e\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c9\"\u003e \u003cp\u003e0.678\u003csup\u003e\u0026sect;\u003c/sup\u003e\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003ctfoot\u003e \u003ctr\u003e\u003ctd colspan=\"9\"\u003eChanges between the baseline and week 12 scores were evaluated within each group using the paired t-test. Change values are highlighted in bold for outcomes that were statistically significant (p\u0026thinsp;\u0026lt;\u0026thinsp;0.05). Differences in change values between the αGPC and placebo groups were assessed using either the Wilcoxon rank-sum test or the two-sample t-test, and the respective p-values are provided. Statistically significant p-values are shown in bold. \u0026Dagger;: Two sample t-test; \u0026sect;: Wilcoxon rank sum test\u003c/td\u003e\u003c/tr\u003e \u003ctr\u003e\u003ctd colspan=\"9\"\u003e\u003cem\u003eαGPC\u003c/em\u003e Choline alphoscerate \u003cem\u003eADAS-cog\u003c/em\u003e, Alzheimer's Disease Assessment Scale-Cognitive Subscale; MoCA\u003cem\u003e-K\u003c/em\u003e, Korean version of the Montreal Cognitive Assessment; \u003cem\u003eK-CWST\u003c/em\u003e, Korean-Color Word Stroop Test\u003c/td\u003e\u003c/tr\u003e \u003c/tfoot\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec14\" class=\"Section2\"\u003e \u003ch2\u003e3.2. Primary outcome (ADAS-cog score)\u003c/h2\u003e \u003cp\u003eAt baseline, no significant differences were observed in the ADAS-cog scores between the αGPC and placebo groups (p\u0026thinsp;=\u0026thinsp;0.329). After 12 weeks, the ADAS-cog scores of both groups significantly decreased from baseline (αGPC: -2.34\u0026thinsp;\u0026plusmn;\u0026thinsp;3.26, p\u0026thinsp;\u0026lt;\u0026thinsp;0.0001; placebo: -0.97\u0026thinsp;\u0026plusmn;\u0026thinsp;2.32, p\u0026thinsp;=\u0026thinsp;0.024). The decrease in the ADAS-cog score was significantly greater in the αGPC group (p\u0026thinsp;\u0026lt;\u0026thinsp;0.048) than in the placebo group. This difference remained statistically significant even when the ADAS-non-cog concentration score was added to the analysis of ADAS-cog score (p\u0026thinsp;=\u0026thinsp;0.037). The results are summarized in Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e and Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003e. Analysis of the memory domain of the ADAS-cog showed that the difference remained statistically significant (p\u0026thinsp;=\u0026thinsp;0.034).\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec15\" class=\"Section2\"\u003e \u003ch2\u003e3.3. Secondary outcomes\u003c/h2\u003e \u003cdiv id=\"Sec16\" class=\"Section3\"\u003e \u003ch2\u003e3.3.1 MoCA-K\u003c/h2\u003e \u003cp\u003eThe MoCA-K includes 7 subscales: visuospatial/executive function, language naming, language-sentence repetition, delayed recall (memory index score), attention, abstraction, and orientation.\u003c/p\u003e \u003cp\u003eAt baseline, no significant difference was observed in the total score of MoCA-K and its subscales between the αGPC and placebo groups. In the αGPC group, there was a significant improvement in the total MoCA-K score from baseline, but the difference in improvement between the two groups was not statistically significant (p\u0026thinsp;=\u0026thinsp;0.105). Among the subscales, there was a significantly greater improvement in language-naming scores in the αGPC group than in the placebo group (p\u0026thinsp;=\u0026thinsp;0.003). Both groups showed improvements in memory (delayed recall) score after 12 weeks; however, there was no significant difference in the degree of improvement between the two groups (p\u0026thinsp;=\u0026thinsp;0.844). The results are summarized in Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e and Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003e.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec17\" class=\"Section3\"\u003e \u003ch2\u003e3.3.2 Visual C.P.T\u003c/h2\u003e \u003cp\u003eVisual C.P.T includes correct response, omission error, commission error, reaction time, and standard deviation of reaction time.\u003c/p\u003e \u003cp\u003eAt baseline, there was no significant difference in any of the measured subscales in visual C.P.T between the αGPC group and placebo group. After 12 weeks, there was a significant decrease in commission error in the αGPC group and standard deviation of reaction time in both groups. However, there was no significant difference in the degree of improvement in any of the items between the two groups. The results are summarized in Supplementary Table\u0026nbsp;1\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec18\" class=\"Section3\"\u003e \u003ch2\u003e3.3.3 K-CWST\u003c/h2\u003e \u003cp\u003eIn the K-CWST, word reading, color naming, word reading of color words (congruent condition), word reading of color words (incongruent condition), and color naming of color words were analyzed considering duration (time) and error frequency.\u003c/p\u003e \u003cp\u003eAt baseline, there was no significant difference between the αGPC and placebo groups on any of the measured subscales of the K-CWST. After 12 weeks, there was a significant decrease in word-reading duration (time) in both groups. Regarding the duration (time) of color naming, there was a significant difference in the decrease between the two groups (p\u0026thinsp;=\u0026thinsp;0.048). The results are summarized in Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e.\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec19\" class=\"Section3\"\u003e \u003ch2\u003e3.3.4 S-IADL\u003c/h2\u003e \u003cp\u003eS-IADL included potential capacity and current performance.\u003c/p\u003e \u003cp\u003eAt baseline, no significant differences were observed in both potential capacity and current performance between the αGPC group and placebo group. After 12 weeks, there was a significant decrease in potential capacity in both groups; however, no significant difference was observed in the degree of decrease between the two groups (p\u0026thinsp;=\u0026thinsp;0.467). The results are summarized in Supplementary Table\u0026nbsp;1\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec20\" class=\"Section3\"\u003e \u003ch2\u003e3.3.5 SCD-Q\u003c/h2\u003e \u003cp\u003eAt baseline, no significant difference in SCD-Q was observed between the αGPC and placebo groups. After 12 weeks, there was a significant decrease in both groups; however, no significant difference was observed in the degree of decrease between the two groups (p\u0026thinsp;=\u0026thinsp;0.343). The results are summarized in Supplementary Table\u0026nbsp;1\u003c/p\u003e \u003c/div\u003e \u003cdiv id=\"Sec21\" class=\"Section3\"\u003e \u003ch2\u003e3.3.6 SGDS-K\u003c/h2\u003e \u003cp\u003eAt baseline, no significant difference in SGDS-K was observed between the αGPC and placebo groups. After 12 weeks, there was a significant decrease in both groups; however, there was no significant difference in the degree of decrease between the two groups (p\u0026thinsp;=\u0026thinsp;0.560). The results are summarized in Supplementary Table\u0026nbsp;1\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv id=\"Sec22\" class=\"Section2\"\u003e \u003ch2\u003e3.4 Adverse events and safety\u003c/h2\u003e \u003cp\u003eNo serious AEs were reported, and no participants discontinued the intervention because of AEs. The most common AEs in both the αGPC and placebo groups were gastrointestinal problems, such as abdominal pain, constipation, dyspepsia, and nausea. All AEs reported in both groups resolved completely. Lists of AEs are presented in Supplementary Table\u0026nbsp;2.\u003c/p\u003e \u003cp\u003eIn terms of blood chemistry, uric acid showed a significant increase when compared to the placebo group (p\u0026thinsp;=\u0026thinsp;0.024). Total cholesterol also exhibited a rising trend compared to the placebo group (p\u0026thinsp;=\u0026thinsp;0.033). However, there were no clinically meaningful changes observed in the test group. Results of biological tests are presented in Supplementary Table\u0026nbsp;3.\u003c/p\u003e \u003c/div\u003e"},{"header":"4. Discussion","content":"\u003cp\u003eThis is the first study on αGPC to explore the safety, tolerability, and efficacy of αGPC in overall healthy individuals with concern of MCI. The results show that αGPC is safe and effective in improving cognitive functions in MCI. The decrease in ADAS-cog score was significantly greater at the 12 weeks post-treatment follow-up assessment in the αGPC group than in the placebo group. A 727 mg dose of SHCog\u0026trade; (600 mg aGPC) once daily was well tolerated by the test group. No serious AEs occurred, and the most frequent side effects included gastrointestinal problems, such as abdominal pain, constipation, dyspepsia, and nausea. However, no significant differences in symptoms were observed between the two groups.\u003c/p\u003e \u003cp\u003eThe primary outcome, the ADAS-cog score, showed an average decrease of 2.34 points from baseline after 12 weeks of oral αGPC administration, which was significantly greater than that in the placebo group. The 2.34-point decrease at 12 weeks in our study indicated a slightly greater cognitive improvement than that observed at 12 weeks (decrease of 1.5\u0026ndash;2.0 ADAS-cog score) in a RCT investigating the effects of 48 weeks of donepezil treatment [\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e]. In a 24-week RCT study investigating the effects of regular exercise on study subjects with MCI, the ADAS-cog score decreased by an average of 1.2 points at the endpoint [\u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e]. While the shorter duration of our study makes it difficult to make direct comparisons with these studies, the improvement in ADAS-cog observed in our study suggests comparable effectiveness.\u003c/p\u003e \u003cp\u003eAnalysis of the memory domain of the ADAS-cog revealed a significant improvement, compared with that of the placebo group. Previous RCTs investigating the effects of choline supplementation (Citicoline) in older adults with memory problems demonstrated significant enhancements in memory function [\u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e]. Another RCT investigating multi-nutrition, including choline, in prodromal AD also revealed significant improvements in the memory domain [\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e]. A review of the effects of αGPC on individuals with cognitive decline highlighted the efficacy of αGPC in memory and attention domains [\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e]. The observed enhancement of memory function by αGPC in our study aligns with these previous findings. Considering the significant relevance of memory decline, particularly in the progression from MCI to AD [\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e], the memory-enhancing effect of αGPC has crucial clinical significance.\u003c/p\u003e \u003cp\u003eAmong the secondary outcome measures in our study, significant improvements in the language-naming subscale of the MoCA-K and the duration (time) of color naming in the K-SVLT were observed in the αGPC group, compared to that in the placebo group. This suggests that αGPC has a particular impact on the language and attention domains. A prospective study evaluating the effects of αGPC on speech recognition in patients with age-related hearing loss indicated its clinical efficacy in central language comprehension, beyond peripheral audibility [\u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e]. A review of the effects of αGPC on patients with dementia highlighted the effect of αGPC on the attention domain [\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e]. The outcomes of our study provide supporting evidence for existing studies on language and attention functions.\u003c/p\u003e \u003cp\u003eNo serious adverse events or drug discontinuation due to AEs were reported in our study. In contrast, an RCT assessing the effects of donepezil on patients with MCI reported drug discontinuation by 42% (165 out of 391) of patients in the donepezil group, with nearly half of them (72 individuals) discontinuing treatment because of AEs [\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e]. Therefore, the tolerability of αGPC observed in our study might be relatively favorable. Our study results provide additional evidence supporting previous research findings that αGPC possesses a favorable safety profile [\u003cspan citationid=\"CR28\" class=\"CitationRef\"\u003e28\u003c/span\u003e]. After 12 weeks of αGPC intake, there was an increase in uric acid and cholesterol levels; however, no subject showed clinically significant changes [\u003cspan citationid=\"CR29\" class=\"CitationRef\"\u003e29\u003c/span\u003e]. Nevertheless, recent cohort studies have reported an association with stroke [\u003cspan citationid=\"CR30\" class=\"CitationRef\"\u003e30\u003c/span\u003e], long-term monitoring will be necessary for future research.\u003c/p\u003e \u003cp\u003eOur study has several limitations. First, the 12-week duration was not enough to capture the full spectrum of αGPC's potential effects on MCI. Cognitive changes could manifest over a more extended period. Furthermore, because of the short study period, there is the possibility of a learning effect. Both the placebo and αGPC groups showed significant ADAS-cog score improvements from baseline to the endpoint. The improvement in the placebo group suggests an increased familiarity with the assessment process over time, regardless of treatment. While the change in the αGPC group was significantly larger, it is noteworthy that the reported 2.34-point reduction might have been influenced by the learning effect, possibly overestimating the cognitive impact of the intervention. Second, the diagnosis of MCI relied solely on clinical assessment tools. Future studies on the effect of αGPC on MCI patient subgrouping patients based on the presence of amyloid plaque will offer a more direct insight into how αGPC affects AD pathology. Studies with longer durations using biomarkers are needed for a more comprehensive understanding of the effect of αGPC on individuals with MCI and the progression to AD. Despite these limitations, our findings suggest the efficacy and safety of αGPC for individuals with aMCI. αGPC is a potential cost-effective therapeutic option for MCI.\u003c/p\u003e \u003cp\u003eThe results of our study demonstrate the efficacy and safety of αGPC for MCI. Over a 12-week period, αGPC treatment led to a notable decrease in the ADAS-cog score by 2.34 points. Furthermore, there were no noticeable differences in side effects or tolerability when compared to the placebo group. These findings highlight αGPC as a promising therapeutic option for MCI.\u003c/p\u003e"},{"header":"Abbreviations","content":"\u003cdiv class=\"DefinitionList\"\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eαGPC\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003ealpha glyceryl phosphorylcholine\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eMCI\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003emild cognitive impairment\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eaMCI\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eamnestic mild cognitive impairment\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eAD\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eAlzheimer\u0026rsquo;s disease\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eADAS\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eAlzheimer\u0026rsquo;s Disease Assessment Scale\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eADAS-cog\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eAlzheimer\u0026rsquo;s Disease Assessment Scale\u0026ndash;cognitive subscale\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eADAS-noncog\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eAlzheimer\u0026rsquo;s Disease Assessment Scale\u0026ndash;non-cognitive subscale\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eAEs\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eadverse effects\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eRCT\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003erandomized control trial\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eSVLT\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eSeoul Verbal Learning Test\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eMoCA-K\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eKorean version of the Montreal Cognitive Assessment\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eVisual C.P.T\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eVisual Continuous Performance Test\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eK-CWST\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eKorean-Color Word Stroop Test\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eS-IADL\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eSeoul-Instrumental Activities of Daily Living\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eSCD-Q\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eSubjective Cognitive Decline Questionnaire\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eSGDS-K\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eKorean version of the Short Form Geriatric Depression Scale\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003cdiv class=\"DefinitionListEntry\"\u003e \u003cdiv class=\"Term\"\u003eITT\u003c/div\u003e \u003cdiv class=\"Description\"\u003e \u003cp\u003eintention-to-treat\u003c/p\u003e \u003c/div\u003e \u003c/div\u003e \u003c/div\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eEthics approval and consent to participate.\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis study was approved by Institutional Review Board of the conducting institutions\u0026nbsp;(Yongin Severance Hospital; 9-2021-0085, Myongji Hospital; 2021-07-035).\u0026nbsp; Informed consent to participate was obtained from all the participants. All methods were carried out in accordance with declaration of Helsinki.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConsent for publication\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eNot applicable.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAvailability of data and materials\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe data used and analysed in this study are available from the corresponding author on reasonable request.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCompeting interests\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThe authors declare no competing interests.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eThis research was supported by the\u003csup\u003e\u0026nbsp;\u003c/sup\u003eSuheung, Osong-eup, Cheongju-si, Chungcheongbuk-do, Republic of Korea; and the HSBio, Jincheon-gun, Chungcheongbuk-do, Republic of Korea; and the\u0026nbsp;Pharmirae Co. Ltd., Seongnam-si, Gyeonggi-do, Republic of Korea.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthors\u0026apos; contributions\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eStudy concept and design: JG, WJ. KD. Data management: KD, JG, WJ. Intervention: JG, WJ, SY, CW, SH Statistical analysis: JW, SY, SJ Analysis and interpretation of data: JW, SJ, WJ. Writing Original draft: JW, JG. All authors read and approved the final manuscript.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAcknowledgements\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eWe want to thank to Sung Hyun Cho, a professional clinical psychologist, for his essential contribution in conducting various neuropsychiatric test throughout the study.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003eOrganization WH. Global status report on the public health response to dementia. 2021.\u003c/li\u003e\n\u003cli\u003eHuey ED, Manly JJ, Tang M-X, Schupf N, Brickman AM, Manoochehri M, et al. Course and etiology of dysexecutive MCI in a community sample. Alzheimer\u0026apos;s \u0026amp; Dementia. 2013;9(6):632-9.\u003c/li\u003e\n\u003cli\u003ePetersen RC. Mild cognitive impairment as a diagnostic entity. Journal of internal medicine. 2004;256(3):183-94.\u003c/li\u003e\n\u003cli\u003eFischer P, Jungwirth S, Zehetmayer S, Weissgram S, Hoenigschnabl S, Gelpi E, et al. Conversion from subtypes of mild cognitive impairment to Alzheimer dementia. Neurology. 2007;68(4):288-91.\u003c/li\u003e\n\u003cli\u003eMatthews FE, Stephan BC, McKeith IG, Bond J, Brayne C, Function MRCC, et al. Two‐year progression from mild cognitive impairment to dementia: to what extent do different definitions agree? Journal of the American Geriatrics Society. 2008;56(8):1424-33.\u003c/li\u003e\n\u003cli\u003ePetersen RC, Lopez O, Armstrong MJ, Getchius TS, Ganguli M, Gloss D, et al. Practice guideline update summary: Mild cognitive impairment: Report of the Guideline Development, Dissemination, and Implementation Subcommittee of the American Academy of Neurology. Neurology. 2018;90(3):126-35.\u003c/li\u003e\n\u003cli\u003eAsaoka D, Xiao J, Takeda T, Yanagisawa N, Yamazaki T, Matsubara Y, et al. Effect of probiotic Bifidobacterium breve in improving cognitive function and preventing brain atrophy in older patients with suspected mild cognitive impairment: results of a 24-week randomized, double-blind, placebo-controlled trial. Journal of Alzheimer\u0026apos;s Disease. 2022;88(1):75-95.\u003c/li\u003e\n\u003cli\u003eAlavi Naeini A, Elmadfa I, Djazayery A, Barekatain M, Aghaye Ghazvini M, Djalali M, et al. The effect of antioxidant vitamins E and C on cognitive performance of the elderly with mild cognitive impairment in Isfahan, Iran: a double-blind, randomized, placebo-controlled trial. European journal of nutrition. 2014;53:1255-62.\u003c/li\u003e\n\u003cli\u003eDoody R, Ferris S, Salloway S, Sun Y, Goldman R, Watkins W, et al. Donepezil treatment of patients with MCI: a 48-week randomized, placebo-controlled trial. Neurology. 2009;72(18):1555-61.\u003c/li\u003e\n\u003cli\u003ePetersen RC, Thomas RG, Grundman M, Bennett D, Doody R, Ferris S, et al. Vitamin E and donepezil for the treatment of mild cognitive impairment. N Engl J Med. 2005;352(23):2379-88.\u003c/li\u003e\n\u003cli\u003eZeisel SH. Nutritional importance of choline for brain development. Journal of the American College of Nutrition. 2004;23(sup6):621S-6S.\u003c/li\u003e\n\u003cli\u003eParnetti L, Amenta F, Gallai V. Choline alphoscerate in cognitive decline and in acute cerebrovascular disease: an analysis of published clinical data. Mech Ageing Dev. 2001;122(16):2041-55.\u003c/li\u003e\n\u003cli\u003eBarbagallo Sangiorgi G, Barbagallo M, Giordano M, Meli M, Panzarasa R. alpha-Glycerophosphocholine in the mental recovery of cerebral ischemic attacks. An Italian multicenter clinical trial. Ann N Y Acad Sci. 1994;717:253-69.\u003c/li\u003e\n\u003cli\u003ePerri RD, Coppola G, Ambrosio L, Grasso A, Puca F, Rizzo M. A multicentre trial to evaluate the efficacy and tolerability of \u0026alpha;-glycerylphosphorylcholine versus cytosine diphosphocholine in patients with vascular dementia. Journal of international medical research. 1991;19(4):330-41.\u003c/li\u003e\n\u003cli\u003eDe Jesus Moreno Moreno M. Cognitive improvement in mild to moderate Alzheimer\u0026apos;s dementia after treatment with the acetylcholine precursor choline alfoscerate: a multicenter, double-blind, randomized, placebo-controlled trial. Clin Ther. 2003;25(1):178-93.\u003c/li\u003e\n\u003cli\u003eSoininen H, Solomon A, Visser PJ, Hendrix SB, Blennow K, Kivipelto M, et al. 24-month intervention with a specific multinutrient in people with prodromal Alzheimer\u0026apos;s disease (LipiDiDiet): a randomised, double-blind, controlled trial. The Lancet Neurology. 2017;16(12):965-75.\u003c/li\u003e\n\u003cli\u003eDoraiswamy P, Bieber F, Kaiser L, Krishnan K, Reuning-Scherer J, Gulanski B. The Alzheimer\u0026apos;s Disease Assessment Scale: patterns and predictors of baseline cognitive performance in multicenter Alzheimer\u0026apos;s disease trials. Neurology. 1997;48(6):1511-7.\u003c/li\u003e\n\u003cli\u003eYoun J, Lee D, Kim K, Lee J, Jhoo J, Lee K, et al. Development of the Korean version of Alzheimer\u0026apos;s disease assessment scale (ADAS‐K). International journal of geriatric psychiatry. 2002;17(9):797-803.\u003c/li\u003e\n\u003cli\u003eKang Y, Park J, Yu K, Lee B, editors. The validity of the Korean-Montreal Cognitive Assessment (K-MoCA) as a screening test for both MCI and VCI. Front Hum Neurosci Conference Abstract: The 20th Annual Rotman Research Institute Conference, The Frontal Lobes; 2010.\u003c/li\u003e\n\u003cli\u003eRiccio CA, Reynolds CR, Lowe P, Moore JJ. The continuous performance test: a window on the neural substrates for attention? Archives of clinical neuropsychology. 2002;17(3):235-72.\u003c/li\u003e\n\u003cli\u003eKim TY, Kim S, Sohn JE, Lee EA, Yoo BG, Lee SC, et al. Development of the Korean Stroop Test and Study of the Validity and the Reliability. Journal of the Korean Geriatrics Society. 2004;8(4):233-40.\u003c/li\u003e\n\u003cli\u003eKU H-M, KIM J-H, KWON E-J, KIM S-H, LEE H-S, KO H-J, et al. A study on the reliability and validity of Seoul-Instrumental Activities of Daily Living (S-IADL). Journal of Korean Neuropsychiatric Association. 2004:189-99.\u003c/li\u003e\n\u003cli\u003eRami L, Mollica MA, Garc\u0026iacute;a-Sanchez C, Salda\u0026ntilde;a J, Sanchez B, Sala I, et al. The subjective cognitive decline questionnaire (SCD-Q): a validation study. Journal of Alzheimer\u0026apos;s Disease. 2014;41(2):453-66.\u003c/li\u003e\n\u003cli\u003eLEE S-C, KIM W-H, CHANG S-M, KIM B-S, LEE D-W, BAE J-N, et al. The use of the Korean version of Short Form Geriatric Depression Scale (SGDS-K) in the community dwelling elderly in Korea. Journal of Korean Geriatric Psychiatry. 2013:37-43.\u003c/li\u003e\n\u003cli\u003eSuzuki T, Shimada H, Makizako H, Doi T, Yoshida D, Ito K, et al. A randomized controlled trial of multicomponent exercise in older adults with mild cognitive impairment. PloS one. 2013;8(4):e61483.\u003c/li\u003e\n\u003cli\u003eSpiers PA, Myers D, Hochanadel GS, Lieberman HR, Wurtman RJ. Citicoline improves verbal memory in aging. Archives of neurology. 1996;53(5):441-8.\u003c/li\u003e\n\u003cli\u003eNa G, Kwak SH, Jang SH, Noh HE, Kim J, Yang S, et al. Supplementary effect of choline alfoscerate on speech recognition in patients with age-related hearing loss: A prospective study in 34 patients (57 ears). Frontiers in Aging Neuroscience. 2021;13:684519.\u003c/li\u003e\n\u003cli\u003eTraini E, Bramanti V, Amenta F. Choline alphoscerate (alpha-glyceryl-phosphoryl-choline) an old choline-containing phospholipid with a still interesting profile as cognition enhancing agent. Current Alzheimer Research. 2013;10(10):1070-9.\u003c/li\u003e\n\u003cli\u003eLi Q, Li X, Wang J, Liu H, Kwong JS-W, Chen H, et al. Diagnosis and treatment for hyperuricemia and gout: a systematic review of clinical practice guidelines and consensus statements. BMJ open. 2019;9(8):e026677.\u003c/li\u003e\n\u003cli\u003eLee G, Choi S, Chang J, Choi D, Son JS, Kim K, et al. Association of L-\u0026alpha; glycerylphosphorylcholine with subsequent stroke risk after 10 years. JAMA network open. 2021;4(11):e2136008-e.\u003c/li\u003e\n\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":true,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"bmc-geriatrics","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"bgtc","sideBox":"Learn more about [BMC Geriatrics](http://bmcgeriatr.biomedcentral.com/)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/bgtc/default.aspx","title":"BMC Geriatrics","twitterHandle":"BMC_series","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"em","reportingPortfolio":"BMC Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true},"keywords":"mild cognitive impairment, choline alphoscerate, SHCog™, cognitive function, memory, language","lastPublishedDoi":"10.21203/rs.3.rs-3488308/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-3488308/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003eBackground\u003c/h2\u003e \u003cp\u003eEffective interventions for overall healthy subjects with mild cognitive impairment are currently limited. Choline alphoscerate (alpha glyceryl phosphorylcholine, αGPC) is a choline-containing phospholipid used to treat cognitive function impairments in specific neurological conditions. This study aimed to investigate the efficacy and safety of αGPC in individuals diagnosed with mild cognitive impairment.\u003c/p\u003e\u003ch2\u003eMethods\u003c/h2\u003e \u003cp\u003eIn this multicenter, randomized, placebo-controlled trial, 100 study subjects with mild cognitive impairment underwent double-blind a 727 mg SHCog\u0026trade; soft capsule (equivalent to 600 mg aGPC) or placebo treatment for 12 weeks. The primary efficacy outcome included changes from baseline on the Alzheimer\u0026rsquo;s Disease Assessment Scale\u0026ndash;cognitive subscale (ADAS-Cog). Safety assessments included regular monitoring of adverse events, and clinical laboratory tests were conducted at baseline and the end of the trial.\u003c/p\u003e\u003ch2\u003eResults\u003c/h2\u003e \u003cp\u003eAfter 12 weeks of αGPC treatment, the ADAS-Cog score decreased by 2.34 points, which was significantly greater than the change observed in the placebo group. No serious AEs were reported, and no study subjects discontinued the intervention because of AEs. There was no significant difference in incidence rate of AEs between the αGPC group and the placebo group.\u003c/p\u003e\u003ch2\u003eConclusion\u003c/h2\u003e \u003cp\u003eThis study suggests that αGPC is a safe and effective intervention for improving cognitive function in study subjects with mild cognitive impairment.\u003c/p\u003e\u003ch2\u003eTrial registration:\u003c/h2\u003e \u003cp\u003eClinical Research Information Service; Osong (Chungcheongbuk-do): Korea Centers for Disease Control and Prevention, Ministry of Health and Welfare (Republic of Korea); KCT0008797; A 12-week, multicenter, randomized, double-blind, placebo-controlled human application study to evaluate the efficacy and safety of SH_CAPK08 on cognitive function improvement in mild cognitive decline.\u003c/p\u003e","manuscriptTitle":"Efficacy and Safety of Choline Alphoscerate for Amnestic Mild Cognitive Impairment: A Randomized Double-Blind Placebo-Controlled Trial","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2023-11-01 20:46:40","doi":"10.21203/rs.3.rs-3488308/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Revision requested","date":"2024-05-31T10:20:47+00:00","index":"","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2024-05-18T14:41:53+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"bfa02d80-9354-4f60-91fe-2f3560c8c9a4","date":"2024-04-26T14:15:36+00:00","index":"hide","fulltext":""},{"type":"editorInvitedReview","content":"","date":"2024-03-26T16:00:28+00:00","index":"hide","fulltext":""},{"type":"reviewerAgreed","content":"b0c245b5-3bf9-4a0b-b011-d3d6f54080af","date":"2024-03-15T19:13:24+00:00","index":"hide","fulltext":""},{"type":"reviewersInvited","content":"","date":"2024-03-13T08:33:48+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2024-02-07T18:18:21+00:00","index":"","fulltext":""},{"type":"editorInvited","content":"","date":"2023-10-31T10:24:52+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2023-10-31T10:23:15+00:00","index":"","fulltext":""},{"type":"submitted","content":"BMC Geriatrics","date":"2023-10-25T02:39:43+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"bmc-geriatrics","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"bgtc","sideBox":"Learn more about [BMC Geriatrics](http://bmcgeriatr.biomedcentral.com/)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/bgtc/default.aspx","title":"BMC Geriatrics","twitterHandle":"BMC_series","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"em","reportingPortfolio":"BMC Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"b4f8508d-beb6-4095-9ebd-94a4ad9757be","owner":[],"postedDate":"November 1st, 2023","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"published-in-journal","subjectAreas":[],"tags":[],"updatedAt":"2024-09-23T16:04:44+00:00","versionOfRecord":{"articleIdentity":"rs-3488308","link":"https://doi.org/10.1186/s12877-024-05366-7","journal":{"identity":"bmc-geriatrics","isVorOnly":false,"title":"BMC Geriatrics"},"publishedOn":"2024-09-19 15:56:59","publishedOnDateReadable":"September 19th, 2024"},"versionCreatedAt":"2023-11-01 20:46:40","video":"","vorDoi":"10.1186/s12877-024-05366-7","vorDoiUrl":"https://doi.org/10.1186/s12877-024-05366-7","workflowStages":[]},"version":"v1","identity":"rs-3488308","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-3488308","identity":"rs-3488308","version":["v1"]},"buildId":"7rjqhiLT3MXkJMwkYKINL","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}