Comparing cortical signatures of atrophy between late-onset and autosomal dominant Alzheimer disease

• Autores: Dincer, Aylin; Gordon, Brian A.; Hari-Raj, Amrita; Keefe, Sarah J.; Flores, Shaney; McKay, Nicole S.; Paulick, Angela M.; Shady Lewis, Kristine E.; Feldman, Rebecca L.; Hornbeck, Russ C.; Allegri, Ricardo Francisco; Ances, Beau M.; Berman, Sarah B.; Brickman, Adam M.; Brooks, William S.; Cash, David M.; Chhatwal, Jasmeer P.; Farlow, Martin R.; Fougère, Christian la; Fox, Nick C.; Fulham, Michael J.; Jack, Clifford R.; Joseph-Mathurin, Nelly; Karch, Celeste M.; Lee, Athene; Levin, Johannes; Masters, Colin L.; McDade, Eric M.; Oh, Hwamee; Perrin, Richard J.
• Año de publicación: 2020
• Idioma: inglés
• Tipo de recurso: artículo
• Materia: ALZHEIMER DISEASE; AMYLOID; AUTOSOMAL DOMINANT ALZHEIMER DISEASE; CORTICAL SIGNATURE; CORTICAL THICKNESS; PRECLINICAL
• Institución: Consejo Nacional de Investigaciones Científicas y Técnicas

Defining a signature of cortical regions of interest preferentially affected by Alzheimer disease (AD) pathology may offer improved sensitivity to early AD compared to hippocampal volume or mesial temporal lobe alone. Since late-onset Alzheimer disease (LOAD) participants tend to have age-related comorbidities, the younger-onset age in autosomal dominant AD (ADAD) may provide a more idealized model of cortical thinning in AD. To test this, the goals of this study were to compare the degree of overlap between the ADAD and LOAD cortical thinning maps and to evaluate the ability of the ADAD cortical signature regions to predict early pathological changes in cognitively normal individuals. We defined and analyzed the LOAD cortical maps of cortical thickness in 588 participants from the Knight Alzheimer Disease Research Center (Knight ADRC) and the ADAD cortical maps in 269 participants from the Dominantly Inherited Alzheimer Network (DIAN) observational study. Both cohorts were divided into three groups: cognitively normal controls (nADRC = 381; nDIAN = 145), preclinical (nADRC = 153; nDIAN = 76), and cognitively impaired (nADRC = 54; nDIAN = 48). Both cohorts underwent clinical assessments, 3T MRI, and amyloid PET imaging with either 11C-Pittsburgh compound B or 18F-florbetapir. To generate cortical signature maps of cortical thickness, we performed a vertex-wise analysis between the cognitively normal controls and impaired groups within each cohort using six increasingly conservative statistical thresholds to determine significance. The optimal cortical map among the six statistical thresholds was determined from a receiver operating characteristic analysis testing the performance of each map in discriminating between the cognitively normal controls and preclinical groups. We then performed within-cohort and cross-cohort (e.g. ADAD maps evaluated in the Knight ADRC cohort) analyses to examine the sensitivity of the optimal cortical signature maps to the amyloid levels using only the cognitively normal individuals (cognitively normal controls and preclinical groups) in comparison to hippocampal volume. We found the optimal cortical signature maps were sensitive to early increases in amyloid for the asymptomatic individuals within their respective cohorts and were significant beyond the inclusion of hippocampus volume, but the cortical signature maps performed poorly when analyzing across cohorts. These results suggest the cortical signature maps are a useful MRI biomarker of early AD-related neurodegeneration in preclinical individuals and the pattern of decline differs between LOAD and ADAD.
Fil: Dincer, Aylin. Washington University in St. Louis; Estados Unidos
Fil: Gordon, Brian A.. Washington University in St. Louis; Estados Unidos
Fil: Hari-Raj, Amrita. Ohio State University; Estados Unidos
Fil: Keefe, Sarah J.. Washington University in St. Louis; Estados Unidos
Fil: Flores, Shaney. Washington University in St. Louis; Estados Unidos
Fil: McKay, Nicole S.. Washington University in St. Louis; Estados Unidos
Fil: Paulick, Angela M.. Washington University in St. Louis; Estados Unidos
Fil: Shady Lewis, Kristine E.. University of Kentucky; Estados Unidos
Fil: Feldman, Rebecca L.. Washington University in St. Louis; Estados Unidos
Fil: Hornbeck, Russ C.. Washington University in St. Louis; Estados Unidos
Fil: Allegri, Ricardo Francisco. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Fundación para la Lucha contra las Enfermedades Neurológicas de la Infancia; Argentina
Fil: Ances, Beau M.. Washington University in St. Louis; Estados Unidos
Fil: Berman, Sarah B.. University of Pittsburgh; Estados Unidos
Fil: Brickman, Adam M.. Columbia University; Estados Unidos
Fil: Brooks, William S.. Neuroscience Research Australia; Australia. University of New South Wales; Australia
Fil: Cash, David M.. UCL Queen Square Institute of Neurology; Reino Unido
Fil: Chhatwal, Jasmeer P.. Harvard Medical School; Estados Unidos
Fil: Farlow, Martin R.. Indiana University; Estados Unidos
Fil: Fougère, Christian la. German Center for Neurodegenerative Diseases; Alemania. University Hospital of Tübingen; Alemania
Fil: Fox, Nick C.. UCL Queen Square Institute of Neurology; Reino Unido
Fil: Fulham, Michael J.. Royal Prince Alfred Hospital; Australia. University of Sydney; Australia
Fil: Jack, Clifford R.. Mayo Clinic; Estados Unidos
Fil: Joseph-Mathurin, Nelly. Washington University in St. Louis; Estados Unidos
Fil: Karch, Celeste M.. Washington University in St. Louis; Estados Unidos
Fil: Lee, Athene. University Brown; Estados Unidos
Fil: Levin, Johannes. German Center for Neurodegenerative Diseases; Alemania. Ludwig Maximilians Universitat; Alemania. Munich Cluster for Systems Neurology; Alemania
Fil: Masters, Colin L.. University of Melbourne; Australia
Fil: McDade, Eric M.. Washington University in St. Louis; Estados Unidos
Fil: Oh, Hwamee. University Brown; Estados Unidos
Fil: Perrin, Richard J.. Washington University in St. Louis; Estados Unidos