A randomized placebo-controlled trial of nicotinamide riboside in older adults with mild cognitive impairment.

Autor: Orr ME; Department of Internal Medicine, Section on Gerontology and Geriatric Medicine, Wake Forest University School of Medicine, 575 Patterson Ave, Winston-Salem, NC, 27101, USA. morr@wakehealth.edu.; Salisbury VA Medical Center, Salisbury, NC, 28144, USA. morr@wakehealth.edu., Kotkowski E; Research Imaging Institute, University of Texas Health Science Center San Antonio, San Antonio, TX, USA., Ramirez P; Sam and Ann Barshop Institute for Longevity and Aging Studies, University of Texas Health Science Center San Antonio, San Antonio, TX, USA.; Department of Cell Systems and Anatomy, University of Texas Health Science Center San Antonio, San Antonio, TX, USA., Bair-Kelps D; Geriatric Research, Education & Clinical Center and Research Service, South Texas Veterans Health Care System, San Antonio, TX, USA., Liu Q; Geriatric Research, Education & Clinical Center and Research Service, South Texas Veterans Health Care System, San Antonio, TX, USA., Brenner C; Department of Diabetes & Cancer Metabolism, City of Hope, Duarte, CA, 91010, USA., Schmidt MS; Department of Biochemistry, Carver College of Medicine, University of Iowa, Iowa City, IA, 52242, USA., Fox PT; Research Imaging Institute, University of Texas Health Science Center San Antonio, San Antonio, TX, USA., Larbi A; Singapore Immunology Network (SIgN), Agency for Science, Technology and Research (A*STAR), 8A Biomedical Grove, Immunos, Singapore, 138648, Republic of Singapore., Tan C; Singapore Immunology Network (SIgN), Agency for Science, Technology and Research (A*STAR), 8A Biomedical Grove, Immunos, Singapore, 138648, Republic of Singapore., Wong G; Singapore Immunology Network (SIgN), Agency for Science, Technology and Research (A*STAR), 8A Biomedical Grove, Immunos, Singapore, 138648, Republic of Singapore., Gelfond J; Sam and Ann Barshop Institute for Longevity and Aging Studies, University of Texas Health Science Center San Antonio, San Antonio, TX, USA.; Geriatric Research, Education & Clinical Center and Research Service, South Texas Veterans Health Care System, San Antonio, TX, USA., Frost B; Sam and Ann Barshop Institute for Longevity and Aging Studies, University of Texas Health Science Center San Antonio, San Antonio, TX, USA.; Department of Cell Systems and Anatomy, University of Texas Health Science Center San Antonio, San Antonio, TX, USA., Espinoza S; Center for Translational Geroscience, Department of Medicine, Cedars-Sinai Medical Center, Los Angeles, CA, USA., Musi N; Center for Translational Geroscience, Department of Medicine, Cedars-Sinai Medical Center, Los Angeles, CA, USA., Powers B; Geriatric Research, Education & Clinical Center and Research Service, South Texas Veterans Health Care System, San Antonio, TX, USA.; Department of Medicine, Division of Geriatrics, Gerontology, and Palliative Medicine, University of Texas Health Science Center San Antonio, San Antonio, USA.
Jazyk: angličtina
Zdroj: GeroScience [Geroscience] 2024 Feb; Vol. 46 (1), pp. 665-682. Date of Electronic Publication: 2023 Nov 23.
DOI: 10.1007/s11357-023-00999-9
Abstrakt: Nicotinamide riboside (NR) increases blood levels of NAD+, a cofactor central to energy metabolism, and improves brain function in some rodent models of neurodegeneration. We conducted a placebo-controlled randomized pilot study with the primary objective of determining safety of NR in older adults with mild cognitive impairment (MCI). Twenty subjects with MCI were randomized to receive placebo or NR using dose escalation to achieve, and maintain, a final dose of 1 g/day over a 10-week study duration. The primary outcome was post-treatment change from baseline measures of cognition (Montreal Cognitive Assessment, MoCA). Predefined secondary outcomes included post-treatment changes in cerebral blood flow (CBF); blood NAD+ levels; and additional neurocognitive, psychometric, and physical performance tests. DNA methylation was assessed in peripheral blood mononuclear cells (PBMCs) as an exploratory outcome. The target NR dose was safely achieved as evidenced by a 2.6-fold increase in blood NAD+ in the NR group (p < 0.001, 95% CI [17.77, 43.49]) with no between-group difference in adverse event reporting. MoCA and other neurocognitive and psychometric metrics remained stable throughout the study. NR reduced CBF in the default mode network (DMN) with greatest differences observed in the left inferior parietal lobe (IPL) (DMN p = 0.013, μ = 0.92, 95% CI [0.23, 1.62]; left IPL p = 0.009, μ = 1.66, 95% CI [0.5, 2.82]). Walking speed in the placebo group significantly improved across the study duration suggestive of a practice effect but did not change in the NR group (p = 0.0402 and p = 0.4698, respectively). Other secondary outcome measures remained stable. Global methylation analyses indicated a modest NR-associated increase in DNA methylation and concomitant reduction in epigenetic age as measured by PhenoAge and GrimAge epigenetic clock analyses. In summary, NR significantly increased blood NAD+ concentrations in older adults with MCI. NR was well tolerated and did not alter cognition. While CBF was reduced by NR treatment, statistical significance would not have withstood multiple comparisons correction. A larger trial of longer duration is needed to determine the potential of NR as a strategy to improve cognition and alter CBF in older adults with MCI. ClinicalTrials.gov NCT02942888.
(© 2023. This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.)
Databáze: MEDLINE
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