Structural disconnectivity and the risk of dementia in the general population
Cremers, Lotte et al. (2021), Structural disconnectivity and the risk of dementia in the general population, Dryad, Dataset, https://doi.org/10.5061/dryad.7wm37pvpq
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 setting.
Methods: Global and tract-specific measures of fractional anisotropy (FA) and mean diffusivity (MD) were obtained in 4,415 non-demented persons (mean age 63.9 years (SD 11.0), 55.0% women) from the prospective population-based Rotterdam Study with brain MRI (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 over 5.4 years of follow-up, 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 AD. Lower global values of FA and higher values of MD associated with an increased risk of dementia (adjusted hazard ratio (95% confidence interval) per standard deviation increase in MD: 1.79 (1.44-2.23), per standard deviation decrease in 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.
Supplemental data with the main manuscript in Neurology.
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See main paper