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Alzheimers Dement. 2018 Mar;14(3):340-351. doi: 10.1016/j.jalz.2017.09.013. Epub 2017 Oct 31.

Cortical microstructural changes along the Alzheimer's disease continuum.

Author information

1
Memory Unit, Department of Neurology, Hospital de la Santa Creu i Sant Pau, Biomedical Research Institute Sant Pau, Universitat Autònoma de Barcelona, Barcelona, Spain; Centro de Investigación Biomédica en Red de Enfermedades Neurodegenerativas (CIBERNED), Spain.
2
Department of Psychiatry, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA; Department of Radiology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
3
Department of Radiology, Hospital del Mar, Barcelona, Spain.
4
Center for Research and Advanced Therapies and Memory Clinic, Fundacion CITA-Alzheimer Fundazioa, Donostia/San Sebastian, Spain.
5
Center for Research and Advanced Therapies and Memory Clinic, Fundacion CITA-Alzheimer Fundazioa, Donostia/San Sebastian, Spain; Donostia Unit, Osatek SA, Donostia University Hospital, San Sebastian, Spain.
6
Servicio de Neurología, Hospital Universitario Marqués de Valdecilla, Santander, Spain.
7
Center for Neuroimmunology, Hospital Clinic Barcelona, IDIBAPS, Barcelona, Spain.
8
Centro de Investigación Biomédica en Red de Enfermedades Neurodegenerativas (CIBERNED), Spain; Center for Research and Advanced Therapies and Memory Clinic, Fundacion CITA-Alzheimer Fundazioa, Donostia/San Sebastian, Spain.
9
Memory Unit, Department of Neurology, Hospital de la Santa Creu i Sant Pau, Biomedical Research Institute Sant Pau, Universitat Autònoma de Barcelona, Barcelona, Spain; Centro de Investigación Biomédica en Red de Enfermedades Neurodegenerativas (CIBERNED), Spain. Electronic address: jfortea@santpau.cat.

Abstract

INTRODUCTION:

Cortical mean diffusivity (MD) and free water fraction (FW) changes are proposed biomarkers for Alzheimer's disease (AD).

METHODS:

We included healthy control subjects (N = 254), mild cognitive impairment (N = 41), and AD dementia (N = 31) patients. Participants underwent a lumbar puncture and a 3 T magnetic resonance imaging. Healthy control subjects were classified following National Institute on Aging-Alzheimer's Association stages (stage 0, N = 220; stage 1, N = 25; and stage 2/3, N = 9). We assessed the cortical MD, cortical FW, and cortical thickness (CTh) changes along the AD continuum.

RESULTS:

Microstructural and macrostructural changes show a biphasic trajectory. Stage 1 subjects showed increased CTh and decreased MD and FW with respect the stage 0 subjects. Stage 2/3 subjects showed decreased CTh and increased cortical MD and FW, changes that were more widespread in symptomatic stages.

DISCUSSION:

These results support a biphasic model of changes in AD, which could affect the selection of patients for clinical trials and the use of magnetic resonance imaging as a surrogate marker of disease modification.

KEYWORDS:

Alzheimer's disease continuum; Amyloid; Biomarkers; CSF; Cortical microstructure; MRI; Tau

PMID:
29080407
DOI:
10.1016/j.jalz.2017.09.013
[Indexed for MEDLINE]

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