Structural disconnectivity and the risk of dementia in the general population

Journal article (2020)

Authors

Lotte G.M. Cremers Erasmus Medical Centre
Lotte G M Cremers Erasmus Medical Centre
Frank J, Wolters Erasmus Medical Centre
Frank J. Wolters Erasmus Medical Centre
Marius De Groot Erasmus Medical Centre
Marius de Groot Erasmus Medical Centre
Mohammad K. Ikram Erasmus Medical Centre
M. Kamran Ikram Erasmus Medical Centre
Aad Van Der Lugt Erasmus Medical Centre
Aad van der Lugt Erasmus Medical Centre
A. Van Der Lugt Erasmus Medical Centre
A. van Der Lugt Erasmus Medical Centre
Aad Van der Lugt Erasmus Medical Centre
Aad van Der Lugt Erasmus Medical Centre
A. van der Lugt Erasmus Medical Centre
A. Van der Lugt Erasmus Medical Centre
Wiro J. Niessen ImPhys/Computational Imaging - AS , ImPhys/Medical Imaging - AS
W.J. Niessen ImPhys/Computational Imaging - AS , ImPhys/Medical Imaging - AS
Wiro Niessen ImPhys/Computational Imaging - AS , ImPhys/Medical Imaging - AS
Wiro J.N. Niessen ImPhys/Computational Imaging - AS , ImPhys/Medical Imaging - AS
WJ Niessen ImPhys/Computational Imaging - AS , ImPhys/Medical Imaging - AS
W. J. Niessen ImPhys/Computational Imaging - AS , ImPhys/Medical Imaging - AS
M. W. Vernooij Erasmus Medical Centre
Meike W. Vernooij Erasmus Medical Centre
M. Arfan Ikram Erasmus Medical Centre
Mohammad Arfan Ikram Erasmus Medical Centre
Research Group
ImPhys/Medical Imaging (AS) (TU Delft)
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Published Date

2020

Language

English

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Faculty

Applied Sciences

Department

ImPhys/Imaging Physics

Research Group

ImPhys/Medical Imaging

Abstract

OBJECTIVE: The disconnectivity hypothesis postulates that partial loss of connecting white matter fibers between brain regions contributes to the development of dementia. Using diffusion MRI to quantify global and tract-specific white matter microstructural integrity, we tested this hypothesis in a longitudinal population-based study. METHODS: Global and tract-specific fractional anisotropy (FA) and mean diffusivity (MD) were obtained in 4,415 people without dementia (mean age 63.9 years, 55.0% women) from the prospective population-based Rotterdam Study with brain MRI between 2005 and 2011. We modeled the association of these diffusion measures with risk of dementia (follow-up until 2016) and with changes on repeated cognitive assessment after on average 5.4 years, adjusting for age, sex, education, macrostructural MRI markers, depressive symptoms, cardiovascular risk factors, and APOE genotype. RESULTS: During a median follow-up of 6.8 years, 101 participants had incident dementia, of whom 83 had clinical Alzheimer disease (AD). Lower global values of FA and higher values of MD were associated with an increased risk of dementia (adjusted hazard ratio [95% confidence interval (CI)] per SD increase for MD 1.79 [1.44-2.23] and FA 0.65 [0.52-0.80]). Similarly, lower global values of FA and higher values of MD related to more cognitive decline in people without dementia (difference in global cognition per SD increase in MD [95% CI] was -0.04 [-0.07 to -0.01]). Associations were most profound in the projection, association, and limbic system tracts. CONCLUSIONS: Structural disconnectivity is associated with an increased risk of dementia and more pronounced cognitive decline in the general population.