title: Physiological fluctuations in white matter are increased in Alzheimer's disease and correlate with neuroimaging and cognitive biomarkers.
abstract: The objective of this study was to determine whether physiological fluctuations in white matter (PFWM) on resting-state functional magnetic resonance images could be used as an index of neurodegeneration and Alzheimer's disease (AD). Using resting-state functional magnetic resonance image data from participants in the Alzheimer's Disease Neuroimaging Initiative, PFWM was compared across cohorts: cognitively healthy, mild cognitive impairment, or probable AD. Secondary regression analyses were conducted between PFWM and neuroimaging, cognitive, and cerebrospinal fluid biomarkers. There was an effect of cohort on PFWM (t = 5.08, degree of freedom [df] = 424, p < 5.7 × 10(-7)), after accounting for nuisance effects from head displacement and global signal (t > 6.16). From the neuroimaging data, PFWM was associated with glucose metabolism (t = -2.93, df = 96, p = 0.004) but not ventricular volume (p < 0.49) or hippocampal volume (p > 0.44). From the cognitive data, PFWM was associated with composite memory (t = -3.24, df = 149, p = 0.0015) but not executive function (p > 0.21). PFWM was not associated with cerebrospinal fluid biomarkers. In one final omnibus model to explain PFWM (n = 124), glucose metabolism (p = 0.04) and cohort (p = 0.008) remained significant, as were global and head motion root-mean-square terms, whereas memory was not (p = 0.64). PFWM likely reflects end-arteriole intracranial pulsatility effects that may provide additional diagnostic potential in the context of AD neurodegeneration.
authors.affiliation: Faculty of Medicine, University of Toronto, Toronto, Ontario, Canada; Heart and Stroke Foundation Canadian Partnership for Stroke Recovery, Sunnybrook Research Institute, Toronto, Ontario, Canada.
authors.forename: Ilia
authors.initials: I
authors.lastname: Makedonov
authors.affiliation: Heart and Stroke Foundation Canadian Partnership for Stroke Recovery, Sunnybrook Research Institute, Toronto, Ontario, Canada; Rotman Research Institute, Baycrest Centre for Geriatric Care, University of Toronto, Toronto, Ontario, Canada; Department of Medical Biophysics, University of Toronto, Toronto, Ontario, Canada.
authors.forename: J Jean
authors.initials: JJ
authors.lastname: Chen
authors.affiliation: Division of Neurology, Department of Medicine, Sunnybrook Health Sciences Centre, University of Toronto, Toronto, Ontario, Canada; Brain Sciences Research Program, Sunnybrook Research Institute, Toronto, Ontario, Canada.
authors.forename: Mario
authors.initials: M
authors.lastname: Masellis
authors.affiliation: Heart and Stroke Foundation Canadian Partnership for Stroke Recovery, Sunnybrook Research Institute, Toronto, Ontario, Canada; Department of Medical Biophysics, University of Toronto, Toronto, Ontario, Canada; Brain Sciences Research Program, Sunnybrook Research Institute, Toronto, Ontario, Canada. Electronic address: bmac@sri.utoronto.ca.
authors.forename: Bradley J
authors.initials: BJ
authors.lastname: MacIntosh
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000175:diagnosis* / Q000473:pathology / Q000503:physiopathology* / Q000523:psychology; D015415:Biomarkers / Q000378:metabolism; D003071:Cognition; D015331:Cohort Studies; D005260:Female; D059907:Functional Neuroimaging; D005947:Glucose / Q000378:metabolism; D006801:Humans; D018810:Magnetic Resonance Angiography; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D012044:Regression Analysis; D012146:Rest / Q000502:physiology; D066127:White Matter / Q000473:pathology* / Q000503:physiopathology*
chemical_list: D015415:Biomarkers; D005947:Glucose
keywords: Alzheimer's disease; Neurodegeneration; Physiological noise; Pulsatility; Resting-state functional MRI; White matter