White matter microstructural abnormalities and default network degeneration are associated with early memory deficit in Alzheimer's disease continuum.

Autor: Ji F; Center for Cognitive Neuroscience, Neuroscience and Behavioural Disorders Program, Duke-National University of Singapore Medical School, Singapore, Singapore., Pasternak O; Departments of Psychiatry and Radiology, Brigham and Women's Hospital, Harvard Medical School, Boston, USA., Ng KK; Center for Cognitive Neuroscience, Neuroscience and Behavioural Disorders Program, Duke-National University of Singapore Medical School, Singapore, Singapore., Chong JSX; Center for Cognitive Neuroscience, Neuroscience and Behavioural Disorders Program, Duke-National University of Singapore Medical School, Singapore, Singapore., Liu S; Center for Cognitive Neuroscience, Neuroscience and Behavioural Disorders Program, Duke-National University of Singapore Medical School, Singapore, Singapore., Zhang L; Center for Cognitive Neuroscience, Neuroscience and Behavioural Disorders Program, Duke-National University of Singapore Medical School, Singapore, Singapore., Shim HY; Center for Cognitive Neuroscience, Neuroscience and Behavioural Disorders Program, Duke-National University of Singapore Medical School, Singapore, Singapore., Loke YM; Center for Cognitive Neuroscience, Neuroscience and Behavioural Disorders Program, Duke-National University of Singapore Medical School, Singapore, Singapore., Tan BY; St Luke's Hospital, Singapore, Singapore., Venketasubramanian N; Raffles Neuroscience Centre, Raffles Hospital, Singapore, Singapore., Chen CL; Department of Pharmacology, National University Health System, Clinical Research Centre, Singapore, Singapore.; Memory, Aging & Cognition Centre, National University Health System, National University of Singapore, Singapore, Singapore., Zhou JH; Center for Cognitive Neuroscience, Neuroscience and Behavioural Disorders Program, Duke-National University of Singapore Medical School, Singapore, Singapore. helen.zhou@duke-nus.edu.sg.; Clinical Imaging Research Centre, the Agency for Science, Technology and Research, Singapore, Singapore. helen.zhou@duke-nus.edu.sg.
Jazyk: angličtina
Zdroj: Scientific reports [Sci Rep] 2019 Mar 18; Vol. 9 (1), pp. 4749. Date of Electronic Publication: 2019 Mar 18.
DOI: 10.1038/s41598-019-41363-2
Abstrakt: Instead of assuming a constant relationship between brain abnormalities and memory impairment, we aimed to examine the stage-dependent contributions of multimodal brain structural and functional deterioration to memory impairment in the Alzheimer's disease (AD) continuum. We assessed grey matter volume, white matter (WM) microstructural measures (free-water (FW) and FW-corrected fractional anisotropy), and functional connectivity of the default mode network (DMN) in 54 amnestic mild cognitive impairment (aMCI) and 46 AD. We employed a novel sparse varying coefficient model to investigate how the associations between abnormal brain measures and memory impairment varied throughout disease continuum. We found lower functional connectivity in the DMN was related to worse memory across AD continuum. Higher widespread white matter FW and lower fractional anisotropy in the fornix showed a stronger association with memory impairment in the early aMCI stage; such WM-memory associations then decreased with increased dementia severity. Notably, the effect of the DMN atrophy occurred in early aMCI stage, while the effect of the medial temporal atrophy occurred in the AD stage. Our study provided evidence to support the hypothetical progression models underlying memory dysfunction in AD cascade and underscored the importance of FW increases and DMN degeneration in early stage of memory deficit.
Databáze: MEDLINE
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