Spatially resolved neural slowing predicts impairment and amyloid burden in Alzheimer's disease.

Autor:	Wiesman AI; Montreal Neurological Institute, McGill University, Montreal, Quebec, Canada.; Department of Neurological Sciences, University of Nebraska Medical Center (UNMC), Omaha, NE, USA., Murman DL; Department of Neurological Sciences, University of Nebraska Medical Center (UNMC), Omaha, NE, USA.; Memory Disorders & Behavioral Neurology Program, UNMC, Omaha, NE, USA., Losh RA; Institute for Human Neuroscience, Boys Town National Research Hospital, Boys Town, NE, USA., Schantell M; Institute for Human Neuroscience, Boys Town National Research Hospital, Boys Town, NE, USA., Christopher-Hayes NJ; Institute for Human Neuroscience, Boys Town National Research Hospital, Boys Town, NE, USA., Johnson HJ; Institute for Human Neuroscience, Boys Town National Research Hospital, Boys Town, NE, USA., Willett MP; Institute for Human Neuroscience, Boys Town National Research Hospital, Boys Town, NE, USA., Wolfson SL; Geriatrics Medicine Clinic, UNMC, Omaha, NE, USA., Losh KL; Institute for Human Neuroscience, Boys Town National Research Hospital, Boys Town, NE, USA., Johnson CM; Department of Radiology, UNMC, Omaha, NE, USA., May PE; Department of Neurological Sciences, University of Nebraska Medical Center (UNMC), Omaha, NE, USA., Wilson TW; Institute for Human Neuroscience, Boys Town National Research Hospital, Boys Town, NE, USA.
Jazyk:	angličtina
Zdroj:	Brain : a journal of neurology [Brain] 2022 Jun 30; Vol. 145 (6), pp. 2177-2189.
DOI:	10.1093/brain/awab430
Abstrakt:	An extensive electrophysiological literature has proposed a pathological 'slowing' of neuronal activity in patients on the Alzheimer's disease spectrum. Supported by numerous studies reporting increases in low-frequency and decreases in high-frequency neural oscillations, this pattern has been suggested as a stable biomarker with potential clinical utility. However, no spatially resolved metric of such slowing exists, stymieing efforts to understand its relation to proteinopathy and clinical outcomes. Further, the assumption that this slowing is occurring in spatially overlapping populations of neurons has not been empirically validated. In the current study, we collected cross-sectional resting state measures of neuronal activity using magnetoencephalography from 38 biomarker-confirmed patients on the Alzheimer's disease spectrum and 20 cognitively normal biomarker-negative older adults. From these data, we compute and validate a new metric of spatially resolved oscillatory deviations from healthy ageing for each patient on the Alzheimer's disease spectrum. Using this Pathological Oscillatory Slowing Index, we show that patients on the Alzheimer's disease spectrum exhibit robust neuronal slowing across a network of temporal, parietal, cerebellar and prefrontal cortices. This slowing effect is shown to be directly relevant to clinical outcomes, as oscillatory slowing in temporal and parietal cortices significantly predicted both general (i.e. Montreal Cognitive Assessment scores) and domain-specific (i.e. attention, language and processing speed) cognitive function. Further, regional amyloid-β accumulation, as measured by quantitative 18F florbetapir PET, robustly predicted the magnitude of this pathological neural slowing effect, and the strength of this relationship between amyloid-β burden and neural slowing also predicted attentional impairments across patients. These findings provide empirical support for a spatially overlapping effect of oscillatory neural slowing in biomarker-confirmed patients on the Alzheimer's disease spectrum, and link this effect to both regional proteinopathy and cognitive outcomes in a spatially resolved manner. The Pathological Oscillatory Slowing Index also represents a novel metric that is of potentially high utility across a number of clinical neuroimaging applications, as oscillatory slowing has also been extensively documented in other patient populations, most notably Parkinson's disease, with divergent spectral and spatial features. (© The Author(s) (2022). Published by Oxford University Press on behalf of the Guarantors of Brain.)
Databáze:	MEDLINE
Externí odkaz:	Zobrazit plný text záznamu