T2 heterogeneity as an in vivo marker of microstructural integrity in medial temporal lobe subfields in ageing and mild cognitive impairment.

Autor: Wearn AR; Bristol Medical School, University of Bristol, Institute of Clinical Neurosciences, Learning & Research Building at Southmead Hospital, Bristol BS10 5NB, UK. Electronic address: Alfie.wearn@bristol.ac.uk., Nurdal V; Bristol Medical School, University of Bristol, Institute of Clinical Neurosciences, Learning & Research Building at Southmead Hospital, Bristol BS10 5NB, UK., Saunders-Jennings E; Bristol Medical School, University of Bristol, Institute of Clinical Neurosciences, Learning & Research Building at Southmead Hospital, Bristol BS10 5NB, UK., Knight MJ; School of Psychological Science, University of Bristol, Bristol, UK., Madan CR; School of Psychology, University of Nottingham, Nottingham, UK., Fallon SJ; National Institute for Health Research Bristol Biomedical Research Centre, University Hospitals Bristol, NHS Foundation Trust and University of Bristol, Bristol, UK., Isotalus HK; Bristol Medical School, University of Bristol, Institute of Clinical Neurosciences, Learning & Research Building at Southmead Hospital, Bristol BS10 5NB, UK., Kauppinen RA; Faculty of Engineering, University of Bristol, Bristol, UK., Coulthard EJ; Bristol Medical School, University of Bristol, Institute of Clinical Neurosciences, Learning & Research Building at Southmead Hospital, Bristol BS10 5NB, UK; Clinical Neurosciences, North Bristol NHS Trust, Bristol, UK.
Jazyk: angličtina
Zdroj: NeuroImage [Neuroimage] 2021 Sep; Vol. 238, pp. 118214. Date of Electronic Publication: 2021 Jun 09.
DOI: 10.1016/j.neuroimage.2021.118214
Abstrakt: A better understanding of early brain changes that precede loss of independence in diseases like Alzheimer's disease (AD) is critical for development of disease-modifying therapies. Quantitative MRI, such as T2 relaxometry, can identify microstructural changes relevant to early stages of pathology. Recent evidence suggests heterogeneity of T2 may be a more informative MRI measure of early pathology than absolute T2. Here we test whether T2 markers of brain integrity precede the volume changes we know are present in established AD and whether such changes are most marked in medial temporal lobe (MTL) subfields known to be most affected early in AD. We show that T2 heterogeneity was greater in people with mild cognitive impairment (MCI; n = 49) compared to healthy older controls (n = 99) in all MTL subfields, but this increase was greatest in MTL cortices, and smallest in dentate gyrus. This reflects the spatio-temporal progression of neurodegeneration in AD. T2 heterogeneity in CA1-3 and entorhinal cortex and volume of entorhinal cortex showed some ability to predict cognitive decline, where absolute T2 could not, however further studies are required to verify this result. Increases in T2 heterogeneity in MTL cortices may reflect localised pathological change and may present as one of the earliest detectible brain changes prior to atrophy. Finally, we describe a mechanism by which memory, as measured by accuracy and reaction time on a paired associate learning task, deteriorates with age. Age-related memory deficits were explained in part by lower subfield volumes, which in turn were directly associated with greater T2 heterogeneity. We propose that tissue with high T2 heterogeneity represents extant tissue at risk of permanent damage but with the potential for therapeutic rescue. This has implications for early detection of neurodegenerative diseases and the study of brain-behaviour relationships.
Competing Interests: Declaration of Competing Interest We declare that none of the authors have competing financial or non-financial interests.
(Copyright © 2021. Published by Elsevier Inc.)
Databáze: MEDLINE
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