NDLI: Amyloid-independent atrophy patterns predict time to progression to dementia in mild cognitive impairment

Content Provider	Springer Nature : BioMed Central
Author	ten Kate, Mara Barkhof, Frederik Visser, Pieter Jelle Teunissen, Charlotte E. Scheltens, Philip van der Flier, Wiesje M. Tijms, Betty M.
Abstract	Background Amyloid pathology in subjects with mild cognitive impairment (MCI) is an important risk factor for progression to dementia due to Alzheimer’s disease. Predicting the onset of dementia is challenging even in the presence of amyloid, as time to progression varies considerably among patients and depends on the onset of neurodegeneration. Survival analysis can account for variability in time to event, but has not often been applied to MRI measurements beyond singular predefined brain regions such as the hippocampus. Here we used a voxel-wise survival analysis to identify in an unbiased fashion brain regions where decreased gray matter volume is associated with time to dementia, and assessed the effects of amyloid on these associations. Methods We included 276 subjects with MCI (mean age 67 ± 8, 41% female, mean Mini-Mental State Examination 26.6 ± 2.4), baseline 3D T1-weighted structural MRI, baseline cerebrospinal fluid (CSF) biomarkers, and prospective clinical follow-up. We fitted for each voxel a proportional Cox hazards regression model to study whether decreased gray matter volume predicted progression to dementia in the total sample, and stratified for baseline amyloid status. Results Dementia at follow-up occurred in 122 (44%) subjects over an average follow-up period of 2.5 ± 1.5 years. Baseline amyloid positivity was associated with progression to dementia (hazard ratio 2.4, p < 0.001). Within amyloid-positive subjects, decreased gray matter volume in the hippocampal, temporal, parietal, and frontal regions was associated with more rapid progression to dementia (median (interquartile range) hazard ratio across significant voxels 1.35 (1.32–1.40)). Repeating the analysis in amyloid-negative subjects revealed similar patterns (median (interquartile range) hazard ratio 1.76 (1.66–1.91)). Conclusions In subjects with MCI, both abnormal amyloid CSF and decreased gray matter volume were associated with future progression to dementia. The spatial pattern of decreased gray matter volume associated with progression to dementia was consistent for amyloid-positive and amyloid-negative subjects.
Related Links	https://alzres.biomedcentral.com/counter/pdf/10.1186/s13195-017-0299-x.pdf
Ending Page	8
Page Count	8
Starting Page	1
File Format	HTM / HTML
ISSN	17589193
DOI	10.1186/s13195-017-0299-x
Journal	Alzheimer's Research & Therapy
Issue Number	1
Volume Number	9
Language	English
Publisher	BioMed Central
Publisher Date	2017-09-12
Access Restriction	Open
Subject Keyword	Neurosciences Neurology Geriatrics Gerontology Geriatric Psychiatry Mild cognitive impairment Alzheimer’s disease Magnetic resonance imaging survival analysis Geriatrics/Gerontology
Content Type	Text
Resource Type	Article
Subject	Neurology Neurology (clinical) Cognitive Neuroscience
Journal Impact Factor	8/2023
5-Year Journal Impact Factor	8.3/2023

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