Cortical phase changes measured using 7‐T MRI in subjects with subjective cognitive impairment, and their association with cognitive function

Abstract

a,bStudies have suggested that, in subjects with subjective cognitive impairment (SCI), Alzheimer's disease (AD)-like changes may occur in the brain. Recently, an in vivo study has indicated the potential of ultra-high-field MRI to visualize amyloidbeta (Aβ)-associated changes in the cortex in patients with AD, manifested by a phase shift on T 2 *-weighted MRI scans. The main aim of this study was to investigate whether cortical phase shifts on T 2 *-weighted images at 7 T in subjects with SCI can be detected, possibly implicating the deposition of Aβ plaques and associated iron. Cognitive tests and T 2 *-weighted scans using a 7-T MRI system were performed in 28 patients with AD, 18 subjects with SCI and 27 healthy controls (HCs). Cortical phase shifts were measured. Univariate general linear modeling and linear regression analysis were used to assess the association between diagnosis and cortical phase shift, and between cortical phase shift and the different neuropsychological tests, adjusted for age and gender. The phase shift (mean, 1.19; range, 1.00-1.35) of the entire cortex in AD was higher than in both SCI (mean, 0.85; range, 0.73-0.99; p < 0.001) and HC (mean, 0.94; range, 0.79-1.10; p < 0.001). No AD-like changes, e.g. increased cortical phase shifts, were found in subjects with SCI compared with HCs. In SCI, a significant association was found between memory function (Wechsler Memory Scale, WMS) and cortical phase shift (β = -0.544, p = 0.007). The major finding of this study is that, in subjects with SCI, an increased cortical phase shift measured at high field is associated with a poorer memory performance, although, as a group, subjects with SCI do not show an increased phase shift compared with HCs. This increased cortical phase shift related to memory performance may contribute to the understanding of SCI as it is still unclear whether SCI is a sign of pre-clinical AD.

Appraising the Role of Iron in Brain Aging and Cognition: Promises and Limitations of MRI Methods

“…For instance, in PD, greater iron content in the basal ganglia and substantia nigra correlates with severity of cognitive and motor impairment (Atasoy et al, 2004; Gorell et al, 1995), as well as progressive increase in symptoms’ severity (Ulla et al, 2013). Greater regional iron deposition has also been associated with cognitive impairment in AD (Zhu et al, 2009; Ding et al, 2009; Qin et al, 2011; Luo et al, 2013; van Rooden et al, 2014). Altered iron homeostasis may explain the pathology of iron in Lewy bodies in PD (Berg et al, 2007), as well as tangles (House et al, 2004), plaques (Quintana et al, 2006; Smith and Perry, 1995) and amyloid burden (El Tannir El Tayara et al, 2006; Rival et al, 2009; Becerril-Ortega et al, 2014) in AD.…”

Treating Alzheimer's disease by targeting iron

“…Higher QSM values, particularly in the hippocampus, are associated with accelerated cognitive decline over 6 years in people with PET‐confirmed Aβ pathology, and along the clinical severity spectrum of AD (Ayton, Fazlollahi, et al, ). In cross‐sectional analysis, the severity of cognitive impairment in people with a clinical diagnosis of AD was associated with QSM (Du et al, ), and T 2 * cortical phase shifts (also sensitive to tissue iron) was associated with cognitive performance in people with subjective memory complaints (van Rooden et al, ) and people with AD (Luo et al, ).…”

Is brain connectome research the future frontier for subjective cognitive decline? A systematic review

“…Nevertheless, people with SCD have been found to exhibit neurodegenerative changes in their brain (Elfgren et al 2003;Babiloni et al 2010;Li et al 2016;Hays et al 2018a;Lazarou et al 2018;Li et al 2018a) in similar regional patterns with people in more advanced stages of the AD continuum (van der Flier et al 2004;Rodda et al 2011;López-Sanz et al 2017aShu et al 2017). Several studies have examined the volumetric differences and brain activity among SCD people (Jessen et al 2006;Babiloni et al 2010;van Rooden et al 2014;Hayes et al 2017), while others have investigated connectivity and communication between brain regions of people with SCD (Bajo et al 2012;Hafkemeijer et al 2013;Wang et al 2013;López-Sanz et al 2017b;Yan et al 2018) by investigating brain connectome and network properties through graph theoretical approaches (Broyd et al 2009;van den Heuvel and Hulshoff Pol 2010;Mevel et al 2011;Sexton et al 2011;Badhwar et al 2017;Contreras et al 2017;Hayes et al 2017;López-Sanz et al 2017b;Shu et al 2017;Verfaillie et al 2018aVerfaillie et al , 2018b). All the above highlight the importance of investigating the brain alterations of people with SCD by using graph network properties.…”