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Effects of spermidine supplementation on cognition and biomarkers in older adults with subjective cognitive decline (SmartAge)-study protocol for a randomized controlled trial.

ABSTRACT: BACKGROUND:Given the global increase in the aging population and age-related diseases, the promotion of healthy aging is one of the most crucial public health issues. This trial aims to contribute to the establishment of effective approaches to promote cognitive and brain health in older individuals with subjective cognitive decline (SCD). Presence of SCD is known to increase the risk of objective cognitive decline and progression to dementia due to Alzheimer's disease. Therefore, it is our primary goal to determine whether spermidine supplementation has a positive impact on memory performance in this at-risk group, as compared with placebo. The secondary goal is to examine the effects of spermidine intake on other neuropsychological, behavioral, and physiological parameters. METHODS:The SmartAge trial is a monocentric, randomized, double-blind, placebo-controlled phase IIb trial. The study will investigate 12?months of intervention with spermidine-based nutritional supplementation (target intervention) compared with 12?months of placebo intake (control intervention). We plan to recruit 100 cognitively normal older individuals with SCD from memory clinics, neurologists and general practitioners in private practice, and the general population. Participants will be allocated to one of the two study arms using blockwise randomization stratified by age and sex with a 1:1 allocation ratio. The primary outcome is the change in memory performance between baseline and post-intervention visits (12?months after baseline). Secondary outcomes include the change in memory performance from baseline to follow-up assessment (18?months after baseline), as well as changes in neurocognitive, behavioral, and physiological parameters (including blood and neuroimaging biomarkers), assessed at baseline and post-intervention. DISCUSSION:The SmartAge trial aims to provide evidence of the impact of spermidine supplementation on memory performance in older individuals with SCD. In addition, we will identify possible neurophysiological mechanisms of action underlying the anticipated cognitive benefits. Overall, this trial will contribute to the establishment of nutrition intervention in the prevention of Alzheimer's disease. TRIAL REGISTRATION:ClinicalTrials.gov, NCT03094546 . Registered 29 March 2017-retrospectively registered. PROTOCOL VERSION:Based on EA1/250/16 version 1.5.

SUBMITTER: Wirth M

PROVIDER: S-EPMC6492385 | biostudies-literature | 2019 May

REPOSITORIES: biostudies-literature

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Effects of spermidine supplementation on cognition and biomarkers in older adults with subjective cognitive decline (SmartAge)-study protocol for a randomized controlled trial.

Wirth Miranka M Schwarz Claudia C Benson Gloria G Horn Nora N Buchert Ralph R Lange Catharina C Köbe Theresa T Hetzer Stefan S Maglione Marta M Michael Eva E Märschenz Stefanie S Mai Knut K Kopp Ute U Schmitz Dietmar D Grittner Ulrike U Sigrist Stephan J SJ Stekovic Slaven S Madeo Frank F Flöel Agnes A

Alzheimer's research & therapy 20190501 1

<h4>Background</h4>Given the global increase in the aging population and age-related diseases, the promotion of healthy aging is one of the most crucial public health issues. This trial aims to contribute to the establishment of effective approaches to promote cognitive and brain health in older individuals with subjective cognitive decline (SCD). Presence of SCD is known to increase the risk of objective cognitive decline and progression to dementia due to Alzheimer's disease. Therefore, it is ...[more]

PMID: 31039826

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Project description:ImportanceDeveloping interventions against age-related memory decline and for older adults experiencing neurodegenerative disease is one of the greatest challenges of our generation. Spermidine supplementation has shown beneficial effects on brain and cognitive health in animal models, and there has been preliminary evidence of memory improvement in individuals with subjective cognitive decline.ObjectiveTo determine the effect of longer-term spermidine supplementation on memory performance and biomarkers in this at-risk group.Design, setting, and participantsThis 12-month randomized, double-masked, placebo-controlled phase 2b trial (the SmartAge trial) was conducted between January 2017 and May 2020. The study was a monocenter trial carried out at an academic clinical research center in Germany. Eligible individuals were aged 60 to 90 years with subjective cognitive decline who were recruited from health care facilities as well as through advertisements in the general population. Data analysis was conducted between January and March 2021.InterventionsOne hundred participants were randomly assigned (1:1 ratio) to 12 months of dietary supplementation with either a spermidine-rich dietary supplement extracted from wheat germ (0.9 mg spermidine/d) or placebo (microcrystalline cellulose). Eighty-nine participants (89%) successfully completed the trial intervention.Main outcomes and measuresPrimary outcome was change in memory performance from baseline to 12-month postintervention assessment (intention-to-treat analysis), operationalized by mnemonic discrimination performance assessed by the Mnemonic Similarity Task. Secondary outcomes included additional neuropsychological, behavioral, and physiological parameters. Safety was assessed in all participants and exploratory per-protocol, as well as subgroup, analyses were performed.ResultsA total of 100 participants (51 in the spermidine group and 49 in the placebo group) were included in the analysis (mean [SD] age, 69 [5] years; 49 female participants [49%]). Over 12 months, no significant changes were observed in mnemonic discrimination performance (between-group difference, -0.03; 95% CI, -0.11 to 0.05; P = .47) and secondary outcomes. Exploratory analyses indicated possible beneficial effects of the intervention on inflammation and verbal memory. Adverse events were balanced between groups.Conclusions and relevanceIn this randomized clinical trial, longer-term spermidine supplementation in participants with subjective cognitive decline did not modify memory and biomarkers compared with placebo. Exploratory analyses indicated possible beneficial effects on verbal memory and inflammation that need to be validated in future studies at higher dosage.Trial registrationClinicalTrials.gov Identifier: NCT03094546.

Project description:BackgroundVascular risk factors, including inflammation, may contribute to dementia development. We investigated the associations between peripheral inflammatory biomarkers and cognitive decline in five domains (memory, construction, language, psychomotor speed, and executive function).MethodsCommunity-dwelling older adults from the Ginkgo Evaluation of Memory Study (n = 1,159, aged 75 or older) free of dementia at baseline were included and followed for up to 7 years. Ten biomarkers were measured at baseline representing different sources of inflammation: vascular inflammation (pentraxin 3 and serum amyloid P), endothelial function (endothelin-1), metabolic function (adiponectin, resistin, and plasminogen activating inhibitor-1), oxidative stress (receptor for advanced glycation end products), and general inflammation (interleukin-6, interleukin-2, and interleukin-10). A combined z-score was created from these biomarkers to represent total inflammation across these sources. We utilized generalized estimating equations that included an interaction term between z-scores and time to assess effect of inflammation on cognitive decline, adjusting for demographics (such as age, race/ethnicity, and sex), cardiovascular risk factors, and apolipoprotein E ε4 carrier status. A Bonferroni-adjusted significance level of .01 was used. We explored associations between individual biomarkers and cognitive decline without adjustment for multiplicity.ResultsThe combined inflammation z-score was significantly associated with memory and psychomotor speed (p < .01). Pentraxin 3, serum amyloid P, endothelin-1, and interleukin-2 were associated with change in at least one cognitive domain (p < .05).ConclusionOur results suggest that total inflammation is associated with memory and psychomotor speed. In particular, systemic inflammation, vascular inflammation, and altered endothelial function may play roles in domain-specific cognitive decline of nondemented individuals.

Project description:Background and Objectives:Subjective cognitive decline (SCD), the self-reported experience of worsening or more frequent confusion or memory loss, may be associated with the development or worsening of chronic conditions or complicating their self-management. The objectives of this study were to (i) establish the prevalence of chronic conditions and multiple chronic conditions among adults with SCD, and (ii) compare the prevalence of chronic conditions among people with and without SCD and SCD-related functional limitations. Research Design and Methods:Data were analyzed from the Cognitive Decline module of the Behavioral Risk Factor Surveillance System administered in 49 states, DC, and Puerto Rico during 2015-2017. Analyses included 220,221 respondents aged 45 years or older who answered the SCD screening question and reported their chronic conditions. Weighted estimates were calculated and chi-square tests were used for comparisons. Results:Persons with a history of stroke, heart disease, and chronic obstructive pulmonary disorder had significantly higher prevalence of SCD compared to those without. The prevalence of having at least one chronic condition was higher among adults with SCD compared to adults without SCD in each age group (45-64 years: 77.4% vs 47.1%, p < .001; ?65 years: 86.3% vs 73.5%, p < .001). Among those with SCD, the prevalence of an SCD-related functional limitation was higher among those with at least one chronic condition compared to those with none (45-64 years: 63.3% vs 42.4%, p < .001; ?65 years: 40.0% vs 25.1%, p < .001). Only half of adults with SCD and a chronic condition had discussed their SCD with a health care professional. Discussion and Implications:SCD and chronic conditions commonly co-occur. Having a chronic condition was associated with greater SCD-related functional limitations. SCD might complicate the management of chronic conditions, and patients and providers should be aware of increased risk for cognitive decline in the presence of chronic diseases.

Dataset Information

Effects of spermidine supplementation on cognition and biomarkers in older adults with subjective cognitive decline (SmartAge)-study protocol for a randomized controlled trial.

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Effects of spermidine supplementation on cognition and biomarkers in older adults with subjective cognitive decline (SmartAge)-study protocol for a randomized controlled trial.

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