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Perilla seed oil in combination with nobiletin-rich ponkan powder enhances cognitive function in healthy elderly Japanese individuals: a possible supplement for brain health in the elderly.
Hashimoto, M, Matsuzaki, K, Maruyama, K, Hossain, S, Sumiyoshi, E, Wakatsuki, H, Kato, S, Ohno, M, Tanabe, Y, Kuroda, Y, et al
Food & function. 2022;(5):2768-2781
Abstract
Perilla (Perilla frutescens) seed oil (PO), rich in α-linolenic acid (ALA), can improve cognitive function in healthy elderly Japanese people. Here, supplements containing either PO alone or PO with nobiletin-rich air-dried immature ponkan powder were examined for their effects on cognitive function in 49 healthy elderly Japanese individuals. Patients were enrolled in a 12-month randomized, double-blind, parallel-armed study. Randomized participants in the PO group received soft gelatin capsules containing 1.47 mL (0.88 g of ALA) of PO daily, and those in the PO + ponkan powder (POPP) group received soft gelatin capsules containing both 1.47 mL of PO and 1.12 g ponkan powder (2.91 mg of nobiletin) daily. At the end of intervention, the POPP group showed significantly higher cognitive index scores than the PO group. The pro-cognitive effects of POPP treatment were accompanied by increases in ALA and docosahexaenoic acid levels in red blood cell plasma membranes, serum brain-derived neurotropic factor (BDNF) levels, and biological antioxidant potential. We demonstrate that 12-month intervention with POPP enhances serum BDNF and antioxidant potential, and may improve age-related cognitive impairment in healthy elderly people by increasing red blood cell ω-3 fatty acid levels. Clinical Trial Registry, UMIN000040863.
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Effect of Advanced Glycation End Products on Cognition in Older Adults with Type 2 Diabetes: Results from a Pilot Clinical Trial.
Lotan, R, Ganmore, I, Livny, A, Itzhaki, N, Waserman, M, Shelly, S, Zacharia, M, Moshier, E, Uribarri, J, Beisswenger, P, et al
Journal of Alzheimer's disease : JAD. 2021;(4):1785-1795
Abstract
BACKGROUND Dietary advanced glycation end-products (AGEs) are linked to cognitive decline. However, clinical trials have not tested the effect of AGEs on cognition in older adults. OBJECTIVE The aim of the current pilot trial was to examine the feasibility of an intervention to reduce dietary AGEs on cognition and on cerebral blood flow (CBF). METHODS The design is a pilot randomized controlled trial of dietary AGEs reduction in older adults with type 2 diabetes. Seventy-five participants were randomized to two arms. The control arm received standard of care (SOC) guidelines for good glycemic control; the intervention arm, in addition to SOC guidelines, were instructed to reduce their dietary AGEs intake. Global cognition and CBF were assessed at baseline and after 6 months of intervention. RESULTS At baseline, we found a reverse association between AGEs and cognitive functioning, possibly reflecting the long-term toxicity of AGEs on the brain. There was a significant improvement in global cognition at 6 months in both the intervention and SOC groups which was more prominent in participants with mild cognitive impairment. We also found that at baseline, higher AGEs were associated with increased CBF in the left inferior parietal cortex; however, 6 months of the AGEs lowering intervention did not affect CBF levels, despite lowering AGEs exposure in blood. CONCLUSION The current pilot trial focused on the feasibility and methodology of intervening through diet to reduce AGEs in older adults with type 2 diabetes. Our results suggest that participants with mild cognitive impairment may benefit from an intensive dietary intervention.
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Impact of Fatty Acid Supplementation on Cognitive Performance among United States (US) Military Officers: The Ranger Resilience and Improved Performance on Phospholipid-Bound Omega-3's (RRIPP-3) Study.
Marriott, BP, Turner, TH, Hibbeln, JR, Newman, JC, Pregulman, M, Malek, AM, Malcolm, RJ, Burbelo, GA, Wismann, JW
Nutrients. 2021;(6)
Abstract
Studies have assessed omega-3 fatty acids and cognitive decline among older adults and cognitive development among children, although less is known about cognitive or neurological effects among young adults. We examined whether omega-3 supplementation from krill oil could improve cognition and resilience among young military officers compared to a control. This double-blind, placebo-controlled trial enrolled 555 officers (mean age 23.4 ± 2.8, 98.6% male) entering the United States (US) Army Infantry Basic Officer Leaders Course (IBOLC) with the intention to complete the US Ranger Course. Volunteer participants consumed eight dietary supplements daily of krill oil containing 2.3 g omega-3 or control (macadamia nut oil) over an approximate 20-week period. Cognitive functioning, resilience, and mood were assessed during a well-rested period at approximately 14 weeks and after a battlefield simulation at 16 weeks. Blood spot samples were collected to monitor compliance and dietary intake was assessed. All hypotheses were tested using both 'Intention to Treat' (ITT) and 'As Per Protocol' (APP) approaches. Of the 555 randomized individuals, 245 (44.1%) completed the study. No statistically significant group-by-time interactions indicating treatment effect were found on any outcomes. Poor compliance was indicated by lower than expected omega-3 elevations in the treatment group, and may have contributed to a failure to detect a response.
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Effects of 12 Weeks Cosmos caudatus Supplement among Older Adults with Mild Cognitive Impairment: A Randomized, Double-Blind and Placebo-Controlled Trial.
You, YX, Shahar, S, Rajab, NF, Haron, H, Yahya, HM, Mohamad, M, Din, NC, Maskat, MY
Nutrients. 2021;(2)
Abstract
Cosmos caudatus (CC) contains high flavonoids and might be beneficial in neuroprotection. It has the potential to prevent neurodegenerative diseases. Therefore, we aimed to investigate the effects of 12 weeks of Cosmos caudatus supplement on cognitive function, mood status, blood biochemical profiles and biomarkers among older adults with mild cognitive impairment (MCI) through a double-blind, placebo-controlled trial. The subjects were randomized into CC supplement (n = 24) and placebo group (n = 24). Each of them consumed one capsule of CC supplement (250 mg of CC/capsule) or placebo (500 mg maltodextrin/capsule) twice daily for 12 weeks. Cognitive function and mood status were assessed at baseline, 6th week, and 12th week using validated neuropsychological tests. Blood biochemical profiles and biomarkers were measured at baseline and 12th week. Two-way mixed analysis of variance (ANOVA) analysis showed significant improvements in mini mental state examination (MMSE) (partial η2 = 0.150, p = 0.049), tension (partial η2 = 0.191, p = 0.018), total mood disturbance (partial η2 = 0.171, p = 0.028) and malondialdehyde (MDA) (partial η2 = 0.097, p = 0.047) following CC supplementation. In conclusion, 12 weeks CC supplementation potentially improved global cognition, tension, total mood disturbance, and oxidative stress among older adults with MCI. Larger sample size and longer period of intervention with incorporation of metabolomic approach should be conducted to further investigate the underlying mechanism of CC supplementation in neuroprotection.
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Diet Effects on Cerebrospinal Fluid Amino Acids Levels in Adults with Normal Cognition and Mild Cognitive Impairment.
Russin, KJ, Nair, KS, Montine, TJ, Baker, LD, Craft, S
Journal of Alzheimer's disease : JAD. 2021;(2):843-853
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Abstract
BACKGROUND Exploration of cerebrospinal fluid (CSF) amino acids and the impact of dietary intake on central levels may provide a comprehensive understanding of the metabolic component of Alzheimer's disease. OBJECTIVE The objective of this exploratory study was to investigate the effects of two diets with varied nutrient compositions on change in CSF amino acids levels in adults with mild cognitive impairment (MCI) and normal cognition (NC). Secondary objectives were to assess the correlations between the change in CSF amino acids and change in Alzheimer's disease biomarkers. METHODS In a randomized, parallel, controlled feeding trial, adults (NC, n = 20; MCI, n = 29) consumed a high saturated fat (SFA)/glycemic index (GI) diet [HIGH] or a low SFA/GI diet [LOW] for 4 weeks. Lumbar punctures were performed at baseline and 4 weeks. RESULTS CSF valine increased and arginine decreased after the HIGH compared to the LOW diet in MCI (ps = 0.03 and 0.04). This pattern was more prominent in MCI versus NC (diet by diagnosis interaction ps = 0.05 and 0.09), as was an increase in isoleucine after the HIGH diet (p = 0.05). Changes in CSF amino acids were correlated with changes in Alzheimer's disease CSF biomarkers Aβ42, total tau, and p-Tau 181, with distinct patterns in the relationships by diet intervention and cognitive status. CONCLUSION Dietary intake affects CSF amino acid levels and the response to diet is differentially affected by cognitive status.
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Effects of Folic Acid and Vitamin B12 Supplementation on Cognitive Impairment and Inflammation in Patients with Alzheimer's Disease: A Randomized, Single-Blinded, Placebo-Controlled Trial.
Chen, H, Liu, S, Ge, B, Zhou, D, Li, M, Li, W, Ma, F, Liu, Z, Ji, Y, Huang, G
The journal of prevention of Alzheimer's disease. 2021;(3):249-256
Abstract
OBJECTIVES To evaluate the combined action of folic acid and vitamin B12 supplementation on cognitive performance and inflammation in patients with Alzheimer's disease (AD). DESIGN This was a randomized, single-blind, placebo-controlled trial. PARTICIPANTS Patients (n=120) diagnosed clinically as probable AD and in stable condition from Tianjin Key Laboratory of Cerebrovascular and Neurodegenerative Diseases. MEASUREMENTS Individuals were randomly divided into the intervention group (n=60, folic acid 1.2 mg/d + vitamin B12 50 μg/d) and the placebo group (n=60). Cognitive performance, blood folate, vitamin B12, one carbon cycle metabolite, and inflammatory cytokine levels were measured at baseline and after 6 months. The data were analyzed using linear mixed models for repeated measures. RESULTS A total of 101 participants (51 in the intervention group and 50 in the placebo group) completed the trial. Folic acid plus vitamin B12 supplementation had a beneficial effect on the MoCA total scores (P=0.029), naming scores (P=0.013), orientation scores (P=0.004), and ADAS-Cog domain score of attention (P=0.008), as compared to those of the control subjects. Moreover, supplementation significantly increased plasma SAM (P<0.001) and SAM/SAH (P<0.001), and significantly decreased the levels of serum Hcy (P<0.001), plasma SAH (P<0.001), and serum TNFα (P<0.001) compared to in the control subjects. CONCLUSIONS Folic acid and vitamin B12 supplementation showed a positive therapeutic effect in AD patients who were not on a folic acid-fortified diet. The findings of this study help to delineate nutrient intervention as far as public health management for the prevention of dementia is concerned.
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The Japan-Multimodal Intervention Trial for Prevention of Dementia (J-MINT): The Study Protocol for an 18-Month, Multicenter, Randomized, Controlled Trial.
Sugimoto, T, Sakurai, T, Akatsu, H, Doi, T, Fujiwara, Y, Hirakawa, A, Kinoshita, F, Kuzuya, M, Lee, S, Matsuo, K, et al
The journal of prevention of Alzheimer's disease. 2021;(4):465-476
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BACKGROUND/OBJECTIVES The Japan-multimodal intervention trial for prevention of dementia (J-MINT) is intended to verify the effectiveness of multi-domain interventions and to clarify the mechanism of cognitive improvement and deterioration by carrying out assessment of dementia-related biomarkers, omics analysis and brain imaging analysis among older adults at high risk of dementia. Moreover, the J-MINT trial collaborates with partnering private enterprises in the implementation of relevant interventional measures. This manuscript describes the study protocol. DESIGN/SETTING Eighteen-month, multi-centered, randomized controlled trial. PARTICIPANTS We plan to recruit 500 older adults aged 65-85 years with mild cognitive impairment. Subjects will be centrally randomized into intervention and control groups at a 1:1 allocation ratio using the dynamic allocation method with all subjects stratified by age, sex, and cognition. INTERVENTION The multi-domain intervention program includes: (1) management of vascular risk factors; (2) group-based physical exercise and self-monitoring of physical activity; (3) nutritional counseling; and (4) cognitive training. Health-related information will be provided to the control group every two months. MEASUREMENTS The primary and secondary outcomes will be assessed at baseline, 6-, 12-, and 18-month follow-up. The primary outcome is the change from baseline to 18 months in a global composite score combining several neuropsychological domains. Secondary outcomes include: cognitive change in each neuropsychological test, incident dementia, changes in blood and dementia-related biomarkers, changes in geriatric assessment including activities of daily living, frailty status and neuroimaging, and number of medications taken. CONCLUSIONS This trial that enlist the support of private enterprises will lead to the creation of new services for dementia prevention as well as to verify the effectiveness of multi-domain interventions for dementia prevention.
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A randomized phase II remote study to assess Bacopa for Gulf War Illness associated cognitive dysfunction: Design and methods of a national study.
Cheema, AK, Wiener, LE, McNeil, RB, Abreu, MM, Craddock, T, Fletcher, MA, Helmer, DA, Ashford, JW, Sullivan, K, Klimas, NG
Life sciences. 2021;:119819
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Abstract
AIMS: Gulf War Illness (GWI) is a chronic, debilitating, multi-symptom condition affecting as many as one-third of the nearly 700,000 U.S. troops deployed to the Middle East during the 1990-1991 Gulf War (GW). The treatment of GWI relies on symptom management. A common challenge in studying the efficacy of interventions for symptom management is participant recruitment related to factors such as the burden of travelling to study sites and the widespread dispersion of Veterans with GWI. The goal of this study is to assess the efficacy of a novel low-risk therapeutic agent, Bacopa monnieri, for cognitive function in Veterans with GWI and to evaluate the utility of a remote patient-centric study design developed to promote recruitment and minimize participant burden. MAIN METHODS To promote effective participant recruitment, we developed a remote patient-centric study design. Participants will be recruited online through social media and through a web-based research volunteer list of GW Veterans. An online assessment platform will be used, and laboratory blood draws will be performed at clinical laboratory sites that are local to participants. Furthermore, the assigned intervention will be mailed to each participant. SIGNIFICANCE These study design adaptations will open participation to Veterans nearly nationwide and reduce administrative costs while maintaining methodologic rigor and participant safety in a randomized, placebo-controlled phase II clinical trial.
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Mindfulness in Motion and Dietary Approaches to Stop Hypertension (DASH) in Hypertensive African Americans.
Wright, KD, Klatt, MD, Adams, IR, Nguyen, CM, Mion, LC, Tan, A, Monroe, TB, Rose, KM, Scharre, DW
Journal of the American Geriatrics Society. 2021;(3):773-778
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Abstract
OBJECTIVES Hypertension increases the risk of developing Alzheimer's disease or related dementias. This pilot study's purpose was to examine the feasibility and acceptability of a novel intervention, Mindfulness in Motion (MIM) and Dietary Approaches to Stop Hypertension DASH (MIM DASH), to improve diet, mindfulness, stress, and systolic blood pressure (BP) in older African Americans with mild cognitive impairment (MCI) and hypertension. DESIGN Cluster randomized controlled trial. SETTING Intergenerational community center in a large metropolitan area. PARTICIPANTS African Americans with MCI and hypertension. Participants were divided into six groups randomized 1:1:1 to the MIM DASH group, attention only (non-hypertensive education) group, or true control group. The MIM DASH and attention only interventions were delivered in 8-weekly 2 hour group sessions. MIM included mindful movements from chair/standing, breathing exercises, and guided meditation. The DASH component used a critical thinking approach of problem solving, goal setting, reflection, and self-efficacy. The true control group received a DASH pamphlet at the end. MEASUREMENTS Feasibility was tracked through enrollment and attendance records; acceptability was assessed through interviews. Blood pressure was measured using the Omron HEM-907XL Monitor. Dietary intake was measured by DASH-Q. Mindfulness was measured by the Cognitive and Affective Mindfulness Scale. Stress was measured by the Perceived Stress Scale. MCI was determined using the Self-Administered Gerocognitive Examination. Data were collected at baseline and 3-months. RESULTS Median session attendance was six for the MIM DASH group and six for the attention only group. There were no changes in diet, mindfulness, or stress. There was a clinically significant reduction in systolic BP in the MIM DASH group (-7.2 mmHg) relative to the attention only group (-.7), and no change between the MIM DASH and true control groups. CONCLUSION Results indicate that the MIM DASH intervention was feasible and culturally acceptable in African Americans with hypertension and MCI.
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REducing SEDENTary Behavior Among Mild to Moderate Cognitively Impaired Assisted Living Residents: A Pilot Randomized Controlled Trial (RESEDENT Study).
Dillon, K, Prapavessis, H
Journal of aging and physical activity. 2021;(1):27-35
Abstract
Older adults in assisted living spend most of their day in sedentary behaviors, which may be detrimental to cognitive function. The primary purpose of this pilot study was to assess the feasibility of using a prompting device to reduce sitting time with light walking among older adults with mild to moderate cognitive impairment residing in an assisted living setting. A secondary purpose was to examine the effectiveness of the intervention on the residents' cognitive function, physical function, and quality of life. The participants (n = 25, mean age = 86.7 [5.3] years) were assigned in clusters into a two-arm 10-week single-site pilot randomized controlled trial. The intervention group was prompted with a watch to interrupt sedentary behaviors and partake in 10 min of light physical activity (i.e., walking) three times a day after a meal. The assessments included hip-worn accelerometers (Actical) and diaries, the Alzheimer's disease assessment scale-cognitive, Timed Up and Go, and the short-form 36 health survey. Adherence was high, as there were no dropouts, and over 70% of the participants completed over 80% of the prescribed physical activity bouts. Significant effects favoring the intervention were shown for all outcomes.