Lotte G M Cremers1,2, Frank J Wolters1,2,3, Marius de Groot1,2,4, M Kamran Ikram5,3, Aad van der Lugt1, Wiro J Niessen1,4,6, Meike W Vernooij1,2, M Arfan Ikram5,3. 1. Department of Radiology and Nuclear Medicine, Erasmus MC, Rotterdam, the Netherlands. 2. Department of Epidemiology, Erasmus MC, Rotterdam, the Netherlands. 3. Department of Neurology, Erasmus MC, Rotterdam, the Netherlands. 4. Department of Medical Informatics, Erasmus MC, Rotterdam, the Netherlands. 5. Department of Epidemiology, Erasmus MC, Rotterdam, the Netherlands m.a.ikram@erasmusmc.nl. 6. Department of Imaging Physics, Faculty of Applied Sciences, Delft University of Technology, Delft, the Netherlands.
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-magnetic resonance imaging (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 non-demented persons (mean age: 63.9 years, 55.0% women) from the prospective population-based Rotterdam Study with brain MRI between 2005-2011. We modelled 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 mean follow-up of 6.7 years, 101 participants had incident dementia, of whom 83 had clinical 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] per standard deviation 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 non-demented individuals (difference in global cognition per standard deviation increase in MD (95% CI) was: -0.04 (-0.07;-0.01)). Associations were most profound in the projection, association and limbic system tracts. CONCLUSIONS: Structural disconnectivity is associated with and an increased risk of dementia and more pronounced cognitive decline in the general population.
OBJECTIVE: The 'disconnectivity hypothesis' postulates that partial loss of connecting white matter fibers between brain regions contributes to the development of dementia. Using diffusion-magnetic resonance imaging (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 non-demented persons (mean age: 63.9 years, 55.0% women) from the prospective population-based Rotterdam Study with brain MRI between 2005-2011. We modelled 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 mean follow-up of 6.7 years, 101 participants had incident dementia, of whom 83 had clinical 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] per standard deviation 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 non-demented individuals (difference in global cognition per standard deviation increase in MD (95% CI) was: -0.04 (-0.07;-0.01)). Associations were most profound in the projection, association and limbic system tracts. CONCLUSIONS: Structural disconnectivity is associated with and an increased risk of dementia and more pronounced cognitive decline in the general population.
Authors: Andrea T Shafer; Owen A Williams; Evian Perez; Yang An; Bennett A Landman; Luigi Ferrucci; Susan M Resnick Journal: Brain Commun Date: 2022-03-01
Authors: Ezequiel Gleichgerrcht; Tanja S Kellermann; Daniel L Drane; Simon S Keller; Carrie R McDonald; Chris Rorden; Jens Jensen; Bernd Weber; Kathryn A Davis; Ruben Kuzniecky; Leonardo Bonilha Journal: Epilepsy Behav Date: 2021-08-07 Impact factor: 3.337