Free water diffusion MRI and executive function with a speed component in healthy aging

Berger, Martin; Pirpamer, Lukas; Hofer, Edith; Ropele, Stefan; Duering, Marco; Gesierich, Benno; Pasternak, Ofer; Enzinger, Christian; Schmidt, Reinhold; Koini, Marisa

doi:10.1016/j.neuroimage.2022.119303

Cited by 10 publications

(10 citation statements)

References 49 publications

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“…While no previous study examined the association between higher FW and cognitive deficits in psychosis, a vast body of literature demonstrated the relationship between extracellular FW and cognitive performance in healthy aging [ 117 , 118 ] and neurodegenerative disorders [ 119 – 121 ] and suggested that FW might be more sensitive than other imaging measures to capture cognition disruption [ 122 ]. Our findings of an association between hippocampal FW but not hippocampal volume with cognition support this notion.…”

Section: Discussionmentioning

confidence: 99%

Matrix metalloproteinase 9 (MMP-9) activity, hippocampal extracellular free water, and cognitive deficits are associated with each other in early phase psychosis

Seitz-Holland,

Alemán-Gómez,

Cho

et al. 2024

Neuropsychopharmacol.

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Increasing evidence points toward the role of the extracellular matrix, specifically matrix metalloproteinase 9 (MMP-9), in the pathophysiology of psychosis. MMP-9 is a critical regulator of the crosstalk between peripheral and central inflammation, extracellular matrix remodeling, hippocampal development, synaptic pruning, and neuroplasticity. Here, we aim to characterize the relationship between plasma MMP-9 activity, hippocampal microstructure, and cognition in healthy individuals and individuals with early phase psychosis. We collected clinical, blood, and structural and diffusion-weighted magnetic resonance imaging data from 39 individuals with early phase psychosis and 44 age and sex-matched healthy individuals. We measured MMP-9 plasma activity, hippocampal extracellular free water (FW) levels, and hippocampal volumes. We used regression analyses to compare MMP-9 activity, hippocampal FW, and volumes between groups. We then examined associations between MMP-9 activity, FW levels, hippocampal volumes, and cognitive performance assessed with the MATRICS battery. All analyses were controlled for age, sex, body mass index, cigarette smoking, and years of education. Individuals with early phase psychosis demonstrated higher MMP-9 activity (p < 0.0002), higher left (p < 0.05) and right (p < 0.05) hippocampal FW levels, and lower left (p < 0.05) and right (p < 0.05) hippocampal volume than healthy individuals. MMP-9 activity correlated positively with hippocampal FW levels (all participants and individuals with early phase psychosis) and negatively with hippocampal volumes (all participants and healthy individuals). Higher MMP-9 activity and higher hippocampal FW levels were associated with slower processing speed and worse working memory performance in all participants. Our findings show an association between MMP-9 activity and hippocampal microstructural alterations in psychosis and an association between MMP-9 activity and cognitive performance. Further, more extensive longitudinal studies should examine the therapeutic potential of MMP-9 modulators in psychosis.

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Section: Discussionmentioning

confidence: 99%

Matrix metalloproteinase 9 (MMP-9) activity, hippocampal extracellular free water, and cognitive deficits are associated with each other in early phase psychosis

Seitz-Holland,

Alemán-Gómez,

Cho

et al. 2024

Neuropsychopharmacol.

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“…The free-water fraction has become a relevant biomarker in neuroimaging, especially for modeling various types of brain damage (Ofori et al, 2015; Bergamino et al, 2021; Carreira Figueiredo et al, 2022). With its proven importance in age-related pathologies and aging processes (Chad et al, 2018; Edde et al, 2020, Berger et al 2022), the evolution of this parameter across the adult lifespan has not been studied in detail. Most works that evaluate the microstructural changes in the brain with age based on diffusion MRI simply use a single component DTI approach, where the FWVF is not taken into account (Burzynska et al, 2010; Bennett et al, 2010; Westlye et al, 2010; Lebel et al, 2012; Cox et al, 2016; Beck et al, 2021).…”

Section: Discussionmentioning

confidence: 99%

Free-water volume fraction increases non-linearly with age in the white matter of the healthy human brain

Pieciak

París

Beck

et al. 2022

Preprint

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The term free-water volume fraction (FWVF) refers to the cerebrospinal and interstitial fluids in the extracellular space of the white matter (WM) of the brain, which has been demonstrated as a sensitive biomarker that correlates with the cognitive performance and the neuropathological processes modifying the interstitial extracellular spaces. It can be quantified by properly fitting the isotropic compartment of the magnetic resonance (MR) signal in diffusion-sensitized sequences. Using N = 287 healthy subjects aged 25-94, this study examines in detail the evolution of the FWVF in the human brain WM across the adult lifespan, which has been previously reported to exhibit a positive trend. We found evidence of a noticeably non-linear gain after the sixth decade of life, with a region-specific variate and varying change rate of the FWVF parameter with age, at the same time a heteroskedastic pattern across the adult lifespan is suggested. On the other hand, the FW-compensated MR signal leads to a region-dependent flattened age-related evolution of the mean diffusivity (MD) and fractional anisotropy (FA), along with a considerable reduction in their variability, as compared to standard studies conducted over the raw MR signal. This way, our study provides a new perspective on the trajectory-based assessment of the brain and explains the source of the variations observed in FA and MD parameters across the lifespan with previous studies with the standard diffusion tensor imaging.

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“…Because executive function has been consistently reported to be associated vascular disease, 17 including FW, 18–20 the clinical outcome measure used by the FW kit is a composite measure of executive function (EFC) derived using item‐response theory (IRT) generated score 21 . Composite scores of executive functions offer advantages such as better reliability, fewer statistical comparisons, and improved power to detect longitudinal change with smaller sample sizes 22,23 .…”

Section: Methodsmentioning

confidence: 99%

MRI free water as a biomarker for cognitive performance: Validation in the MarkVCID consortium

Maillard

Hillmer

et al. 2022

Alz & Dem Diag Ass & Dis Mo

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Introduction To evaluate the clinical validity of free water (FW), a diffusion tensor imaging–based biomarker kit proposed by the MarkVCID consortium, by investigating the association between mean FW (mFW) and executive function. Methods Baseline mFW was related to a baseline composite measure of executive function (EFC), adjusting for relevant covariates, in three MarkVCID sub‐cohorts, and replicated in five, large, independent legacy cohorts. In addition, we tested whether baseline mFW predicted accelerated EFC score decline (mean follow‐up time: 1.29 years). Results Higher mFW was found to be associated with lower EFC scores in MarkVCID legacy and sub‐cohorts ( p ‐values < 0.05). In addition, higher baseline mFW was associated significantly with accelerated decline in EFC scores ( p = 0.0026). Discussion mFW is a sensitive biomarker of cognitive decline, providing a strong clinical rational for its use as a marker of white matter (WM) injury in multi‐site observational studies and clinical trials of vascular cognitive impairment and dementia (VCID).

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Free water diffusion MRI and executive function with a speed component in healthy aging

Cited by 10 publications

References 49 publications

Matrix metalloproteinase 9 (MMP-9) activity, hippocampal extracellular free water, and cognitive deficits are associated with each other in early phase psychosis

Matrix metalloproteinase 9 (MMP-9) activity, hippocampal extracellular free water, and cognitive deficits are associated with each other in early phase psychosis

Free-water volume fraction increases non-linearly with age in the white matter of the healthy human brain

MRI free water as a biomarker for cognitive performance: Validation in the MarkVCID consortium

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