Dissociable diffusion MRI patterns of white matter microstructure and connectivity in Alzheimer's disease spectrum.
Recent efforts using diffusion tensor imaging (DTI) have documented white matter (WM) alterations in Alzheimer's disease (AD). The full potential of whole-brain DTI, however, has not been fully exploited as studies have focused on individual microstructural indices independently. In patients with AD (n = 79), mild (MCI, n = 55) and subjective (SCI, n = 30) cognitive impairment, we applied linked independent component analysis (LICA) to model inter-subject variability across five complementary DTI measures (fractional anisotropy (FA), axial/radial/mean diffusivity, diffusion tensor mode), two crossing fiber measures estimated using a multi-compartment crossing-fiber model reflecting the volume fraction of the dominant (f1) and non-dominant (f2) diffusion orientation, and finally, connectivity density obtained from full-brain probabilistic tractography. The LICA component explaining the largest data variance was highly sensitive to disease severity (AD < MCI < SCI) and revealed widespread coordinated decreases in FA and f1 with increases in all diffusivity measures in AD. Additionally, it reflected regional coordinated decreases and increases in f2, mode and connectivity density, implicating bidirectional alterations of crossing fibers in the fornix, uncinate fasciculi, corpus callosum and major sensorimotor pathways. LICA yielded improved diagnostic classification performance compared to univariate region-of-interest features. Our results document coordinated WM microstructural and connectivity alterations in line with disease severity across the AD continuum.
NORMENT, KG Jebsen Centre for Psychosis Research, Division of Mental Health and Addiction, Oslo University Hospital &Institute of Clinical Medicine, University of Oslo, Norway.
Nhat Trung
NT
Doan
NORMENT, KG Jebsen Centre for Psychosis Research, Division of Mental Health and Addiction, Oslo University Hospital &Institute of Clinical Medicine, University of Oslo, Norway.|Department of Medicine, Diakonhjemmet hospital, Oslo, Norway.
Andreas
A
Engvig
Norwegian National Advisory Unit on Ageing and Health, Vestfold Hospital Trust, Tønsberg, Norway.|Department of Geriatric Medicine, The Memory Clinic, Oslo University Hospital, Oslo, Norway.
Karin
K
Persson
NORMENT, KG Jebsen Centre for Psychosis Research, Division of Mental Health and Addiction, Oslo University Hospital &Institute of Clinical Medicine, University of Oslo, Norway.
Dag
D
Alnæs
NORMENT, KG Jebsen Centre for Psychosis Research, Division of Mental Health and Addiction, Oslo University Hospital &Institute of Clinical Medicine, University of Oslo, Norway.
Tobias
T
Kaufmann
NORMENT, KG Jebsen Centre for Psychosis Research, Division of Mental Health and Addiction, Oslo University Hospital &Institute of Clinical Medicine, University of Oslo, Norway.|Department of Psychology, University of Oslo, Oslo, Norway.
Jaroslav
J
Rokicki
NORMENT, KG Jebsen Centre for Psychosis Research, Division of Mental Health and Addiction, Oslo University Hospital &Institute of Clinical Medicine, University of Oslo, Norway.
Aldo
A
Córdova-Palomera
NORMENT, KG Jebsen Centre for Psychosis Research, Division of Mental Health and Addiction, Oslo University Hospital &Institute of Clinical Medicine, University of Oslo, Norway.
Torgeir
T
Moberget
Norwegian National Advisory Unit on Ageing and Health, Vestfold Hospital Trust, Tønsberg, Norway.|Department of Geriatric Medicine, The Memory Clinic, Oslo University Hospital, Oslo, Norway.
Anne
A
Brækhus
Norwegian National Advisory Unit on Ageing and Health, Vestfold Hospital Trust, Tønsberg, Norway.|Department of Geriatric Medicine, The Memory Clinic, Oslo University Hospital, Oslo, Norway.
Maria Lage
ML
Barca
Norwegian National Advisory Unit on Ageing and Health, Vestfold Hospital Trust, Tønsberg, Norway.|Department of Geriatric Medicine, The Memory Clinic, Oslo University Hospital, Oslo, Norway.
Knut
K
Engedal
NORMENT, KG Jebsen Centre for Psychosis Research, Division of Mental Health and Addiction, Oslo University Hospital &Institute of Clinical Medicine, University of Oslo, Norway.
Ole A
OA
Andreassen
Norwegian National Advisory Unit on Ageing and Health, Vestfold Hospital Trust, Tønsberg, Norway.|Centre for Old Age Psychiatric Research, Innlandet Hospital Trust, Ottestad, Norway.
Geir
G
Selbæk
NORMENT, KG Jebsen Centre for Psychosis Research, Division of Mental Health and Addiction, Oslo University Hospital &Institute of Clinical Medicine, University of Oslo, Norway.|Department of Psychology, University of Oslo, Oslo, Norway.
Lars T
LT
Westlye
D000368:Aged; D000544:Alzheimer Disease / Q000000981:diagnostic imaging*; D000076103:Biological Variation, Individual; D063132:Connectome; D005260:Female; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D066127:White Matter / Q000000981:diagnostic imaging*