Biphasic cortical macro- and microstructural changes in autosomal dominant Alzheimer's disease
Por:
Montal, V, Vilaplana, E, Pegueroles, J, Bejanin, A, Alcolea, D, Carmona-Iragui, M, Clarimon, J, Levin, J, Cruchaga, C, Graff-Radford, NR, Noble, JM, Lee, JH, Allegri, R, Karch, CM, Laske, C, Schofield, PR, Salloway, S, Ances, B, Benzinger, T, McDale, E, Bateman, R, Blesa, R, Sanchez-Valle, R, Lleo, A, Fortea, J, DIAN
Publicada:
1 abr 2021
Resumen:
INTRODUCTION A biphasic model for brain structural changes in preclinical Alzheimer's disease (AD) could reconcile some conflicting and paradoxical findings in observational studies and anti-amyloid clinical trials.
METHODS In this study we tested this model fitting linear versus quadratic trajectories and computed the timing of the inflection points vertexwise of cortical thickness and cortical diffusivity-a novel marker of cortical microstructure-changes in 389 participants from the Dominantly Inherited Alzheimer Network.
RESULTS In early preclinical AD, between 20 and 15 years before estimated symptom onset, we found increases in cortical thickness and decreases in cortical diffusivity followed by cortical thinning and cortical diffusivity increases in later preclinical and symptomatic stages. The inflection points 16 to 19 years before estimated symptom onset are in agreement with the start of tau biomarker alterations.
DISCUSSION These findings confirm a biphasic trajectory for brain structural changes and have direct implications when interpreting magnetic resonance imaging measures in preventive AD clinical trials.
Filiaciones:
Montal, V:
Univ Autonoma Barcelona, Biomed Res Inst St Pau, Hosp Santa Creu & St Pau, Dept Neurol,St Pau Memory Unit, Barcelona, Spain
Ctr Biomed Invest Network Neurodegenerat Dis CIBE, Madrid, Spain
Vilaplana, E:
Univ Autonoma Barcelona, Biomed Res Inst St Pau, Hosp Santa Creu & St Pau, Dept Neurol,St Pau Memory Unit, Barcelona, Spain
Ctr Biomed Invest Network Neurodegenerat Dis CIBE, Madrid, Spain
Pegueroles, J:
Univ Autonoma Barcelona, Biomed Res Inst St Pau, Hosp Santa Creu & St Pau, Dept Neurol,St Pau Memory Unit, Barcelona, Spain
Ctr Biomed Invest Network Neurodegenerat Dis CIBE, Madrid, Spain
Bejanin, A:
Univ Autonoma Barcelona, Biomed Res Inst St Pau, Hosp Santa Creu & St Pau, Dept Neurol,St Pau Memory Unit, Barcelona, Spain
Ctr Biomed Invest Network Neurodegenerat Dis CIBE, Madrid, Spain
Alcolea, D:
Univ Autonoma Barcelona, Biomed Res Inst St Pau, Hosp Santa Creu & St Pau, Dept Neurol,St Pau Memory Unit, Barcelona, Spain
Ctr Biomed Invest Network Neurodegenerat Dis CIBE, Madrid, Spain
Carmona-Iragui, M:
Univ Autonoma Barcelona, Biomed Res Inst St Pau, Hosp Santa Creu & St Pau, Dept Neurol,St Pau Memory Unit, Barcelona, Spain
Ctr Biomed Invest Network Neurodegenerat Dis CIBE, Madrid, Spain
Fdn Catalana Sindrome Down, Barcelona Down Med Ctr, Barcelona, Spain
Clarimon, J:
Univ Autonoma Barcelona, Biomed Res Inst St Pau, Hosp Santa Creu & St Pau, Dept Neurol,St Pau Memory Unit, Barcelona, Spain
Ctr Biomed Invest Network Neurodegenerat Dis CIBE, Madrid, Spain
Levin, J:
Ludwig Maximilians Univ Munchen, Dept Neurol, Munich, Germany
Munich Cluster Syst Neurol SyNergy, German Ctr Neurodegenerat Dis, Munich, Germany
Munich Cluster Syst Neurol SyNergy, Munich, Germany
Cruchaga, C:
Washington Univ, Sch Med, Dept Neurol, St Louis, MO 63110 USA
Hope Ctr Neurol Disorders, St Louis, MO USA
Washington Univ, Sch Med, NeuroGen & Informat, St Louis, MO USA
Washington Univ, Sch Med, Knight Alzheimers Dis Res Ctr, St Louis, MO USA
Graff-Radford, NR:
Mayo Clin, Dept Neurol, Jacksonville, FL 32224 USA
Noble, JM:
Columbia Univ, Dept Neurol, Taub Inst Res Alzheimers Dis & Aging Brain, Irving Med Ctr, New York, NY USA
Lee, JH:
Univ Ulsan, Dept Neurol, Asan Med Ctr, Coll Med, Seoul, South Korea
Allegri, R:
Inst Neurol Res Fleni, Dept Cognit Neurol, Buenos Aires, DF, Argentina
Karch, CM:
Washington Univ, Sch Med, Dept Psychiat, St Louis, MO 63110 USA
Laske, C:
German Ctr Neurodegenerat Dis DZNE, Tubingen, Germany
Univ Tubingen, Hertie Inst Clin Brain Res, Sect Dementia Res, Tubingen, Germany
Univ Tubingen, Dept Psychiat & Psychotherapy, Tubingen, Germany
Schofield, PR:
Neurosci Res Australia, Sydney, NSW, Australia
Univ New South Wales, Sch Med Sci, Sydney, NSW, Australia
Salloway, S:
Butler Hosp, Neurol & Memory & Aging Program, Providence, RI 02906 USA
Ances, B:
Washington Univ, Sch Med, Dept Neurol, St Louis, MO 63110 USA
Hope Ctr Neurol Disorders, St Louis, MO USA
Washington Univ, Sch Med, Knight Alzheimers Dis Res Ctr, St Louis, MO USA
Washington Univ, Dept Radiol, St Louis, MO 63110 USA
Benzinger, T:
Washington Univ, Sch Med, Knight Alzheimers Dis Res Ctr, St Louis, MO USA
Washington Univ, Dept Radiol, St Louis, MO 63110 USA
McDale, E:
Washington Univ, Sch Med, Dept Neurol, St Louis, MO 63110 USA
Washington Univ, Sch Med, Knight Alzheimers Dis Res Ctr, St Louis, MO USA
Bateman, R:
Washington Univ, Sch Med, Dept Neurol, St Louis, MO 63110 USA
Hope Ctr Neurol Disorders, St Louis, MO USA
Washington Univ, Sch Med, Knight Alzheimers Dis Res Ctr, St Louis, MO USA
Blesa, R:
Univ Autonoma Barcelona, Biomed Res Inst St Pau, Hosp Santa Creu & St Pau, Dept Neurol,St Pau Memory Unit, Barcelona, Spain
Ctr Biomed Invest Network Neurodegenerat Dis CIBE, Madrid, Spain
Sanchez-Valle, R:
Univ Barcelona, Inst Invest Biomed August Pi & Sunyer IDIBAPS, Alzheimers Dis & Other Cognit Disorders Unit, Hosp Clin,Fdn Clin Recerca Biomed, Barcelona, Spain
Lleo, A:
Univ Autonoma Barcelona, Biomed Res Inst St Pau, Hosp Santa Creu & St Pau, Dept Neurol,St Pau Memory Unit, Barcelona, Spain
Ctr Biomed Invest Network Neurodegenerat Dis CIBE, Madrid, Spain
Fortea, J:
Univ Autonoma Barcelona, Biomed Res Inst St Pau, Hosp Santa Creu & St Pau, Dept Neurol,St Pau Memory Unit, Barcelona, Spain
Ctr Biomed Invest Network Neurodegenerat Dis CIBE, Madrid, Spain
Fdn Catalana Sindrome Down, Barcelona Down Med Ctr, Barcelona, Spain
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