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@ARTICLE{Schwarz:164588,
      author       = {Schwarz, Claudia and Benson, Gloria S and Horn, Nora and
                      Wurdack, Katharina and Grittner, Ulrike and Schilling, Ralph
                      and Märschenz, Stefanie and Köbe, Theresa and Hofer,
                      Sebastian J and Magnes, Christoph and Stekovic, Slaven and
                      Eisenberg, Tobias and Sigrist, Stephan and Schmitz, Dietmar
                      and Wirth, Miranka and Madeo, Frank and Flöel, Agnes},
      title        = {{E}ffects of {S}permidine {S}upplementation on {C}ognition
                      and {B}iomarkers in {O}lder {A}dults {W}ith {S}ubjective
                      {C}ognitive {D}ecline: {A} {R}andomized {C}linical {T}rial.},
      journal      = {JAMA network open},
      volume       = {5},
      number       = {5},
      issn         = {2574-3805},
      address      = {Chicago, Ill.},
      publisher    = {American Medical Association},
      reportid     = {DZNE-2022-01137},
      pages        = {e2213875},
      year         = {2022},
      note         = {(CC BY)},
      abstract     = {Developing 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.To determine
                      the effect of longer-term spermidine supplementation on
                      memory performance and biomarkers in this at-risk group.This
                      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.One 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.Primary 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.A 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.In 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.ClinicalTrials.gov Identifier: NCT03094546.},
      keywords     = {Aged / Animals / Biomarkers / Cognition: physiology /
                      Cognitive Dysfunction: drug therapy / Dietary Supplements /
                      Female / Humans / Inflammation / Neurodegenerative Diseases
                      / Spermidine: pharmacology / Spermidine: therapeutic use /
                      Biomarkers (NLM Chemicals) / Spermidine (NLM Chemicals)},
      cin          = {AG Teipel / AG Wirth / AG Donix},
      ddc          = {610},
      cid          = {I:(DE-2719)1510100 / I:(DE-2719)1710011 /
                      I:(DE-2719)1710008},
      pnm          = {353 - Clinical and Health Care Research (POF4-353)},
      pid          = {G:(DE-HGF)POF4-353},
      typ          = {PUB:(DE-HGF)16},
      pmc          = {pmc:PMC9136623},
      pubmed       = {pmid:35616942},
      doi          = {10.1001/jamanetworkopen.2022.13875},
      url          = {https://pub.dzne.de/record/164588},
}