Comparisons of neurodegeneration over time between healthy ageing and Alzheimer's disease cohorts via Bayesian inference

• Published in: BMJ open 2017-02, Vol.7 (2), p.e012174-e012174
• Main Authors: Cespedes, Marcela I, Fripp, Jurgen, McGree, James M, Drovandi, Christopher C, Mengersen, Kerrie, Doecke, James D
• Format: Article
• Language: English
• Subjects: Age; Aged; Aged, 80 and over; Aging; Alzheimer Disease - diagnostic imaging; Alzheimer's disease; Apolipoproteins; Asymptomatic; Bayes Theorem; Bayesian analysis; Biomarkers; Brain - diagnostic imaging; Brain - pathology; Brain research; Case-Control Studies; Cerebral Ventricles - diagnostic imaging; Cerebral Ventricles - pathology; Cognitive ability; Cognitive Dysfunction - diagnostic imaging; Dementia; Estimates; Female; Gender differences; Healthy Aging; Hippocampus - diagnostic imaging; Hippocampus - pathology; Humans; Longitudinal Studies; Male; Medical imaging; Middle Aged; Neurodegeneration; Neurodegenerative Diseases - diagnostic imaging; Neuroimaging; Neurological disorders; Neurology; Organ Size; Pathology; Time Factors
• ISSN: 2044-6055; 2044-6055
• DOI: 10.1136/bmjopen-2016-012174

ObjectivesIn recent years, large-scale longitudinal neuroimaging studies have improved our understanding of healthy ageing and pathologies including Alzheimer's disease (AD). A particular focus of these studies is group differences and identification of participants at risk of deteriorating to a worse diagnosis. For this, statistical analysis using linear mixed-effects (LME) models are used to account for correlated observations from individuals measured over time. A Bayesian framework for LME models in AD is introduced in this paper to provide additional insight often not found in current LME volumetric analyses.Setting and participantsLongitudinal neuroimaging case study of ageing was analysed in this research on 260 participants diagnosed as either healthy controls (HC), mild cognitive impaired (MCI) or AD. Bayesian LME models for the ventricle and hippocampus regions were used to: (1) estimate how the volumes of these regions change over time by diagnosis, (2) identify high-risk non-AD individuals with AD like degeneration and (3) determine probabilistic trajectories of diagnosis groups over age.ResultsWe observed (1) large differences in the average rate of change of volume for the ventricle and hippocampus regions between diagnosis groups, (2) high-risk individuals who had progressed from HC to MCI and displayed similar rates of deterioration as AD counterparts, and (3) critical time points which indicate where deterioration of regions begins to diverge between the diagnosis groups.ConclusionsTo the best of our knowledge, this is the first application of Bayesian LME models to neuroimaging data which provides inference on a population and individual level in the AD field. The application of a Bayesian LME framework allows for additional information to be extracted from longitudinal studies. This provides health professionals with valuable information of neurodegeneration stages, and a potential to provide a better understanding of disease pathology.