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. 2022 Mar 1;4(2):fcac051.
doi: 10.1093/braincomms/fcac051. eCollection 2022.

Accelerated decline in white matter microstructure in subsequently impaired older adults and its relationship with cognitive decline

Andrea T Shafer  1 , Owen A Williams  1   2 , Evian Perez  3 , Yang An  1 , Bennett A Landman  4 , Luigi Ferrucci  5 , Susan M Resnick  1
Affiliations

Accelerated decline in white matter microstructure in subsequently impaired older adults and its relationship with cognitive decline

Andrea T Shafer et al. Brain Commun. .

Abstract

Little is known about a longitudinal decline in white matter microstructure and its associations with cognition in preclinical dementia. Longitudinal diffusion tensor imaging and neuropsychological testing were performed in 50 older adults who subsequently developed mild cognitive impairment or dementia (subsequently impaired) and 200 cognitively normal controls. Rates of white matter microstructural decline were compared between groups using voxel-wise linear mixed-effects models. Associations between change in white matter microstructure and cognition were examined. Subsequently impaired individuals had a faster decline in fractional anisotropy in the right inferior fronto-occipital fasciculus and bilateral splenium of the corpus callosum. A decline in right inferior fronto-occipital fasciculus fractional anisotropy was related to a decline in verbal memory, visuospatial ability, processing speed and mini-mental state examination. A decline in bilateral splenium fractional anisotropy was related to a decline in verbal fluency, processing speed and mini-mental state examination. Accelerated regional white matter microstructural decline is evident during the preclinical phase of mild cognitive impairment/dementia and is related to domain-specific cognitive decline.

Keywords: cognition; diffusion tensor imaging; longitudinal change; preclinical Alzheimer’s disease; white matter microstructure.

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Figures

Graphical Abstract
Graphical Abstract
Figure 1
Figure 1
White matter clusters showing accelerated microstructural decline in the SI group. Line graphs show modelled trajectories of a decline in FA for clusters in the right IFOF, right SCC and left SCC. The black panel shows axial slices where clusters with accelerated FA decline were found for the SI group in the right IFOF (top) and bilateral SCC (bottom) highlighted in red and indicated by the yellow ellipsoids.
Figure 2
Figure 2
Associations between change in FA and change in cognition. The figure shows the relationship between the rate of change in the right IFOF and the rate of change in processing speed (left panel), verbal memory (middle panel) and MMSE (right panel). The effects of baseline age, sex and race were removed from the estimated slopes for FA and cognition. Thus, the residuals are the estimated slopes of annual change in z-scores removing effects of baseline age, sex, and race. Shaded areas indicate 95% confidence intervals.
See this image and copyright information in PMC

References

    1. Nitrini R, Bottino CMC, Albala C, et al. Prevalence of dementia in Latin America: A collaborative study of population-based cohorts. Int Psychogeriatr. 2009;21(4):622–630. - PMC - PubMed
    1. Armstrong NM, Huang C-W, Williams OA, et al. Sex differences in the association between amyloid and longitudinal brain volume change in cognitively normal older adults. NeuroImage. 2019;22:101769. - PMC - PubMed
    1. Jack CR Jr, Bennett DA, Blennow K, et al. NIA-AA Research Framework: Toward a biological definition of Alzheimer’s disease. Alzheimers Dement. 2018;14(4):535–562. - PMC - PubMed
    1. Sperling RA, Aisen PS, Beckett LA, et al. Toward defining the preclinical stages of Alzheimer’s disease: Recommendations from the National Institute on Aging-Alzheimer’s Association workgroups on diagnostic guidelines for Alzheimer’s disease. Alzheimers Dement. 2011;7(3):280–292. - PMC - PubMed
    1. Villemagne VL, Burnham S, Bourgeat P, et al. Amyloid β deposition, neurodegeneration, and cognitive decline in sporadic Alzheimer’s disease: A prospective cohort study. Lancet Neurol. 2013;12(4):357–367. - PubMed

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