Microstructural Neuroimaging of Frailty in Cognitively Normal Older Adults.

Qu Tian,Bennett A Landman,Luigi Ferrucci,Susan M Resnick,Owen A Williams

doi:10.3389/fmed.2020.546344

Abstract

Physical frailty is an age-related clinical syndrome that is associated with multiple adverse health outcomes, including cognitive impairment and dementia. Recent studies have shown that frailty is associated with specific volumetric neuroimaging characteristics. Whether brain microstructural characteristics, particularly gray matter, associated with frailty exist and what their spatial distribution is have not been explored. We identified 670 participants of the Baltimore Longitudinal Study of Aging who were aged 60 and older and cognitively normal and who had concurrent data on frailty and regional microstructural neuroimaging markers by diffusion tensor imaging (DTI), including mean diffusivity (MD) of gray matter and fractional anisotropy (FA) of white matter. We identified neuroimaging markers that were associated with frailty status (non-frail, pre-frail, frail) and further examined differences between three groups using multivariate linear regression (non-frail = reference). Models were adjusted for age, sex, race, years of education, body mass index, scanner type, and Apolipoprotein E e4 carrier status. Compared to the non-frail participants, those who were frail had higher MD in the medial frontal cortex, several subcortical regions (putamen, caudate, thalamus), anterior cingulate cortex, and a trend of lower FA in the body of the corpus callosum. Those who were pre-frail also had higher MD in the putamen and a trend of lower FA in the body of the corpus callosum. Our study demonstrates for the first time that the microstructure of both gray and white matter differs by frailty status in cognitively normal older adults. Brain areas were not widespread but mostly localized in frontal and subcortical motor areas and the body of the corpus callosum. Whether changes in brain microstructure precede future frailty development warrants further investigation.

Highlights

Physical frailty is an age-related clinical syndrome that has been both cross-sectionally and prospectively associated with multiple adverse health outcomes, such as disability, hospitalization, and mortality, but in the initial stage, it is thought to be potentially reversible [1,2,3,4]
We focused on fractional anisotropy (FA) of white matter regions of interest (ROIs) and mean diffusivity (MD) of gray matter ROIs
We identified diffusion tensor imaging (DTI)-based neuroimaging markers that were being univariately associated with frailty status using simple linear regression

Summary

Introduction

Physical frailty is an age-related clinical syndrome that has been both cross-sectionally and prospectively associated with multiple adverse health outcomes, such as disability, hospitalization, and mortality, but in the initial stage, it is thought to be potentially reversible (i.e., pre-frail stage) [1,2,3,4]. Neuroimaging studies have shown that cerebrovascular damage, gray matter atrophy, as well as brain β-amyloid, may contribute to the pathophysiology of frailty. The severity of frailty status has been associated with a greater number of cerebral microbleeds [5], greater gray matter atrophy [6,7,8], higher white matter hyperintensity volume and infarcts [7,8,9,10], and higher brain β-amyloid burden [11, 12]. A few longitudinal studies have shown that higher white matter hyperintensity volume or infarcts [13, 14], higher brain β-amyloid burden [11], and neuronal loss [14] are associated with the progression of frailty. A few studies examining regional brain atrophy with frailty suggest that brain areas important for motor function and execution may play a key role in frailty, such as selected areas in frontal, temporal, and parietal lobes, anterior cingulate cortex, subcortical areas, and cerebellum [6, 15]

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Results

Conclusion