Biphasic cortical macro- and microstructural changes in autosomal dominant Alzheimer's disease

MONTAL VICTOR; VILAPLANA EDUARD; PEGUEROLES JORDI; BEJANIN ALEXANDRE; ALCOLEA DANIEL; CARMONA IRAGUI MARIA; CLARIMON JORDI; LEVIN JOANES; CRUCHAGA CARLOS; GRAFF-RADFORD, NEILL R; NOBLE, JAMES M; LEE JAE-HONG; ALLEGRI RICARDO FRANCISCO; ET AL.

ALZHEIMERS & DEMENTIA

ELSEVIER SCIENCE INC

Lugar: Amsterdam; Año: 2021 vol. 17 p. 618 - 628

1552-5260

INTRODUCTION:A biphasic model for brain structural changes in preclinical Alzheimer Disease could reconcile some conflicting and paradoxical findings in observational studies and anti-amyloid clinical trialsMETHODS:In this study we tested this model fitting linear vs 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’s Network.RESULTS:In early preclinical AD, between 20 to 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 MRI measures in preventive AD clinical trials.