TY - JOUR
T1 - Clinicopathologic Factors Associated With Reversion to Normal Cognition in Patients With Mild Cognitive Impairment
AU - Li, Zonghua
AU - Heckman, Michael G.
AU - Kanekiyo, Takahisa
AU - Martens, Yuka A.
AU - Day, Gregory S.
AU - Vassilaki, Maria
AU - Liu, Chia Chen
AU - Bennett, David A.
AU - Petersen, Ronald C.
AU - Zhao, Na
AU - Bu, Guojun
N1 - Funding Information:
The MCSA cohort was supported by the NIH (U01 AG006786, P50 AG016574, P30 AG062677, R01 AG011378, R01 AG041851, R01 NS097495), the Alexander Family Alzheimer's Disease Research Professorship of the Mayo Clinic, the Liston Award, the Schuler Foundation, the GHR Foundation, and the Mayo Foundation for Medical Education and Research and was made possible by the Rochester Epidemiology Project (R01 AG034676). The ROSMAP cohort was supported by NIA grants P30AG10161, R01AG15819, and R01AG17917. The NACC cohort was supported by NIA/NIH grant U01 AG016976. NACC data are contributed by the NIA-funded ADRCs: P30 AG019610 (PI Eric Reiman, MD), P30 AG013846 (PI Neil Kowall, MD), P50 AG008702 (PI Scott Small, MD), P50 AG025688 (PI Allan Levey, MD, PhD), P50 AG047266 (PI Todd Golde, MD, PhD), P30 AG010133 (PI Andrew Saykin, PsyD), P50 AG005146 (PI Marilyn Albert, PhD), P50 AG005134 (PI Bradley Hyman, MD, PhD), P50 AG016574 (PI Ronald Petersen, MD, PhD), P50 AG005138 (PI Mary Sano, PhD), P30 AG008051 (PI Thomas Wisniewski, MD), P30 AG013854 (PI Robert Vassar, PhD), P30 AG008017 (PI Jeffrey Kaye, MD), P30 AG010161 (PI David Bennett, MD), P50 AG047366 (PI Victor Henderson, MD, MS), P30 AG010129 (PI Charles DeCarli, MD), P50 AG016573 (PI Frank LaFerla, PhD), P50 AG005131 (PI James Brewer, MD, PhD), P50 AG023501 (PI Bruce Miller, MD), P30 AG035982 (PI Russell Swerdlow, MD), P30 AG028383 (PI Linda Van Eldik, PhD), P30 AG053760 (PI Henry Paulson, MD, PhD), P30 AG010124 (PI John Trojanowski, MD, PhD), P50 AG005133 (PI Oscar Lopez, MD), P50 AG005142 (PI Helena Chui, MD), P30 AG012300 (PI Roger Rosenberg, MD), P30 AG049638 (PI Suzanne Craft, PhD), P50 AG005136 (PI Thomas Grabowski, MD), P50 AG033514 (PI Sanjay Asthana, MD, FRCP), P50 AG005681 (PI John Morris, MD), and P50 AG047270 (PI Stephen Strittmatter, MD, PhD). This work is partially supported by the NIH grants RF1AG057181, R37AG027924, and RF1AG046205, and a Cure Alzheimer's Fund grant to G.B. and the Coins for Alzheimer's Research Trust (CART) Foundation to N.Z. The funders had no role in the design or conduct of the study; collection, management, analysis, or interpretation of the data; preparation, review, or approval of the manuscript; or the decision to submit the manuscript for publication.
Funding Information:
G. Bu consults for SciNeuro and Lexeo; has consulted for AbbVie, E-Scape, Eisai, and Vida Ventures; is on the scientific advisory board for Kisbee Therapeutics; and receives funding from NIH and Cure Alzheimer's Fund. G.S. Day's research is supported by NIH, the Alzheimer's Association, and Chan Zuckerberg Initiative; he consults for Parabon Nanolabs Inc., as a Topic Editor (Dementia) for DynaMed (EBSCO) and as the Clinical Director of the Anti-NMDA Receptor Encephalitis Foundation (Canada; uncompensated); is the co-Project PI for a clinical trial in anti-NMDAR encephalitis, which receives support from Horizon Pharmaceuticals; has developed educational materials for PeerView Media, Inc., and Continuing Education Inc.; and owns stock in ANI Pharmaceuticals. M. Vassilaki has received research funding from F. Hoffmann-La Roche and Biogen. She currently consults for F. Hoffmann-La Roche, receives research funding from NIH and has equity ownership in Abbott Laboratories, Johnson & Johnson, Medtronic, and Amgen. R. Petersen consults for Nestle, Merck, Roche, Biogen, and Eisai; and is on the Data Safety Monitoring Board of Genentech. The remaining authors report no disclosures relevant to the manuscript. Go to Neurology.org/N for full disclosures.
Publisher Copyright:
© American Academy of Neurology.
PY - 2022/5/17
Y1 - 2022/5/17
N2 - Background and ObjectivesTo identify clinicopathologic factors contributing to mild cognitive impairment (MCI) reversion to normal cognition.MethodsWe analyzed 3 longitudinal cohorts in this study: the Mayo Clinic Study of Aging (MCSA), the Religious Orders Study and Memory and Aging Project (ROSMAP), and the National Alzheimer's Coordinating Center (NACC). Demographic characteristics and clinical outcomes were compared between patients with MCI with or without an experience of reversion to normal cognition (referred to as reverters and nonreverters, respectively). We also compared longitudinal changes in cortical thickness, glucose metabolism, and amyloid and tau load in a subcohort of reverters and nonreverters in MCSA with MRI or PET imaging information from multiple visits.ResultsWe identified 164 (56.4%) individuals in MCSA, 508 (66.8%) individuals in ROSMAP, and 280 (34.1%) individuals in NACC who experienced MCI reversion to normal cognition. Cox proportional hazards regression models showed that MCI reverters had an increased chance of being cognitively normal at the last visit in MCSA (HR 3.31, 95% CI 2.14-5.12), ROSMAP (HR 3.72, 95% CI 2.50-5.56), and NACC (HR 9.29, 95% CI 6.45-13.40) and a reduced risk of progression to dementia (HR 0.12, 95% CI 0.05-0.29 in MCSA; HR 0.41, 95% CI 0.32-0.53 in ROSMAP; and HR 0.29, 95% CI 0.21-0.40 in NACC). Compared with MCI nonreverters, reverters had better-preserved cortical thickness (β = 0.082, p <0.001) and glucose metabolism (β = 0.119, p = 0.001) and lower levels of amyloid, albeit statistically nonsignificant (β =-0.172, p = 0.090). However, no difference in tau load was found between reverters and nonreverters (β = 0.073, p = 0.24).DiscussionMCI reversion to normal cognition is likely attributed to better-preserved cortical structure and glucose metabolism.
AB - Background and ObjectivesTo identify clinicopathologic factors contributing to mild cognitive impairment (MCI) reversion to normal cognition.MethodsWe analyzed 3 longitudinal cohorts in this study: the Mayo Clinic Study of Aging (MCSA), the Religious Orders Study and Memory and Aging Project (ROSMAP), and the National Alzheimer's Coordinating Center (NACC). Demographic characteristics and clinical outcomes were compared between patients with MCI with or without an experience of reversion to normal cognition (referred to as reverters and nonreverters, respectively). We also compared longitudinal changes in cortical thickness, glucose metabolism, and amyloid and tau load in a subcohort of reverters and nonreverters in MCSA with MRI or PET imaging information from multiple visits.ResultsWe identified 164 (56.4%) individuals in MCSA, 508 (66.8%) individuals in ROSMAP, and 280 (34.1%) individuals in NACC who experienced MCI reversion to normal cognition. Cox proportional hazards regression models showed that MCI reverters had an increased chance of being cognitively normal at the last visit in MCSA (HR 3.31, 95% CI 2.14-5.12), ROSMAP (HR 3.72, 95% CI 2.50-5.56), and NACC (HR 9.29, 95% CI 6.45-13.40) and a reduced risk of progression to dementia (HR 0.12, 95% CI 0.05-0.29 in MCSA; HR 0.41, 95% CI 0.32-0.53 in ROSMAP; and HR 0.29, 95% CI 0.21-0.40 in NACC). Compared with MCI nonreverters, reverters had better-preserved cortical thickness (β = 0.082, p <0.001) and glucose metabolism (β = 0.119, p = 0.001) and lower levels of amyloid, albeit statistically nonsignificant (β =-0.172, p = 0.090). However, no difference in tau load was found between reverters and nonreverters (β = 0.073, p = 0.24).DiscussionMCI reversion to normal cognition is likely attributed to better-preserved cortical structure and glucose metabolism.
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U2 - 10.1212/WNL.0000000000200387
DO - 10.1212/WNL.0000000000200387
M3 - Article
C2 - 35314499
AN - SCOPUS:85130637785
SN - 0028-3878
VL - 98
SP - E2036-E2045
JO - Neurology
JF - Neurology
IS - 20
ER -