Microstructural degeneration underlies executive dysfunction after stroke

ABSTRACTObjectiveExecutive dysfunction affects 40% of stroke patients and is associated with poor quality of life. Stroke severity and lesion volume rarely predict whether a patient will have executive dysfunction. Stroke typically occurs on a background of cerebrovascular burden, which impacts cognition and brain network structural integrity. We investigated whether measures of white matter microstructural integrity and cerebrovascular risk factors better explain executive dysfunction than markers of stroke severity.MethodsWe used structural equation modelling to examine multivariate relationships between cerebrovascular risk, white matter microstructural integrity (fractional anisotropy and mean diffusivity), stroke characteristics and executive dysfunction in 126 stroke patients (mean age 68.4 years), three months post-stroke, and compared to 40 age- and sex-matched control participants. Executive function was measured using the Trail Making Tests, Clock Drawing task and Rey Complex Figure copy task. Microstructural integrity was estimated using a standard pipeline to process diffusion weighted images.ResultsExecutive function was below what would be expected for age and education level in stroke patients (t-test compared to controls t(79)=5.75, p<0.001). A multivariate structural equation model illustrated the complex relationship between executive function, white matter integrity, stroke characteristics and cerebrovascular risk. Pearson’s correlations confirmed a stronger relationship between executive dysfunction and white matter integrity, than executive dysfunction and stroke severity. Mediation analysis showed the relationship between executive function and white matter integrity is mediated by cerebrovascular burden.InterpretationWhite matter microstructural degeneration of the superior longitudinal fasciculus in the executive control network better explains executive dysfunction than markers of stroke severity.

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Microstructural degeneration and cerebrovascular risk burden underlying executive dysfunction after stroke

Scientific Reports ◽

10.1038/s41598-020-75074-w ◽

2020 ◽

Vol 10 (1) ◽

Author(s):

Michele Veldsman ◽

Emilio Werden ◽

Natalia Egorova ◽

Mohamed Salah Khlif ◽

Amy Brodtmann

Keyword(s):

Risk Factors ◽

Executive Function ◽

White Matter ◽

Structural Equation ◽

Executive Dysfunction ◽

White Matter Integrity ◽

Stroke Severity ◽

Stroke Patients ◽

Cerebrovascular Risk Factors ◽

Cerebrovascular Risk

Abstract Executive dysfunction affects 40% of stroke patients, but is poorly predicted by characteristics of the stroke itself. Stroke typically occurs on a background of cerebrovascular burden, which impacts cognition and brain network structural integrity. We used structural equation modelling to investigate whether measures of white matter microstructural integrity (fractional anisotropy and mean diffusivity) and cerebrovascular risk factors better explain executive dysfunction than markers of stroke severity. 126 stroke patients (mean age 68.4 years) were scanned three months post-stroke and compared to 40 age- and sex-matched control participants on neuropsychological measures of executive function. Executive function was below what would be expected for age and education level in stroke patients as measured by the organizational components of the Rey Complex Figure Test, F(3,155) = 17, R2 = 0.25, p < 0.001 (group significant predictor at p < 0.001) and the Trail-Making Test (B), F(3,157) = 3.70, R2 = 0.07, p < 0.01 (group significant predictor at p < 0.001). A multivariate structural equation model illustrated the complex relationship between executive function, white matter integrity, stroke characteristics and cerebrovascular risk (root mean square error of approximation = 0.02). Pearson’s correlations confirmed a stronger relationship between executive dysfunction and white matter integrity (r = − 0.74, p < 0.001), than executive dysfunction and stroke severity (r = 0.22, p < 0.01). The relationship between executive function and white matter integrity is mediated by cerebrovascular burden. White matter microstructural degeneration of the superior longitudinal fasciculus in the executive control network better explains executive dysfunction than markers of stroke severity. Executive dysfunction and incident stroke can be both considered manifestations of cerebrovascular risk factors.

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Association between microstructural integrity of frontostriatal tracts and school functioning: ADHD symptoms and executive function as mediators

Psychological Medicine ◽

10.1017/s0033291714001664 ◽

2014 ◽

Vol 45 (3) ◽

pp. 529-543 ◽

Cited By ~ 14

Author(s):

S. S. Gau ◽

W.-L. Tseng ◽

W.-Y. I. Tseng ◽

Y.-H. Wu ◽

Y.-C. Lo

Keyword(s):

Executive Function ◽

White Matter ◽

Response Inhibition ◽

Neuropsychological Test ◽

School Functioning ◽

White Matter Integrity ◽

Future Research ◽

Adhd Symptoms ◽

Diffusion Spectrum Imaging ◽

Microstructural Integrity

BackgroundDeficits in executive function (EF), impaired school functioning and altered white matter integrity in frontostriatal networks have been associated with attention-deficit/hyperactivity disorder (ADHD). However, relationships between impairments in these areas are unclear. Using a sample of youths with and without ADHD, this study examined the association between microstructural integrity of frontostriatal tracts and school dysfunction and the mediating roles of EF and ADHD symptoms in this association.MethodThe sample included 32 Taiwanese youths with ADHD and 32 age-, sex-, handedness- and IQ-matched typically-developing (TD) youths. Participants were assessed using psychiatric interviews, parent reports on ADHD symptoms and school functioning, and EF measures from the Cambridge Neuropsychological Test Automated Battery (CANTAB). The frontostriatal tracts were reconstructed by diffusion spectrum imaging (DSI) tractography and were subdivided into four functionally distinct segments: caudate–dorsolateral, caudate–medial prefrontal, caudate–orbitofrontal and caudate–ventrolateral tracts.ResultsYouths with ADHD, relative to TD youths, showed altered white matter integrity in all four bilateral pairs of frontostriatal tracts (decreased general fractional anisotropy, GFA), had poor attention, vigilance and response inhibition, and showed impaired school functioning. Altered microstructural integrity in frontostriatal tracts was significantly associated with school dysfunction, which was mediated by EF measures of attention/vigilance and response inhibition in addition to inattention and hyperactivity symptoms.ConclusionsOur findings demonstrate an association between white matter integrity in the frontostriatal networks and school functioning and suggest that EF deficits and ADHD symptoms may be the mediating mechanisms for this association. Future research is needed to test the directionality and specificity of this finding.

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The Longitudinal Decline of White Matter Microstructural Integrity in Behavioral Variant Frontotemporal Dementia and Its Association with Executive Function

SSRN Electronic Journal ◽

10.2139/ssrn.3218688 ◽

2018 ◽

Author(s):

Junhong Yu ◽

Tatia M.C. Lee

Keyword(s):

Executive Function ◽

White Matter ◽

Frontotemporal Dementia ◽

Behavioral Variant Frontotemporal Dementia ◽

Microstructural Integrity

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Association of White Matter Integrity With Executive Function and Antidepressant Treatment Outcome in Patients With Late-Life Depression

American Journal of Geriatric Psychiatry ◽

10.1016/j.jagp.2021.01.004 ◽

2021 ◽

Author(s):

Xiaofu He ◽

Elena Pueraro ◽

Yoojean Kim ◽

Carolina Montes Garcia ◽

Ben Maas ◽

...

Keyword(s):

Treatment Outcome ◽

Executive Function ◽

White Matter ◽

Antidepressant Treatment ◽

Late Life ◽

White Matter Integrity ◽

Late Life Depression

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White matter integrity in dyskinetic cerebral palsy: Relationship with intelligence quotient and executive function

NeuroImage Clinical ◽

10.1016/j.nicl.2017.05.005 ◽

2017 ◽

Vol 15 ◽

pp. 789-800 ◽

Cited By ~ 9

Author(s):

Olga Laporta-Hoyos ◽

Kerstin Pannek ◽

Júlia Ballester-Plané ◽

Lee B. Reid ◽

Élida Vázquez ◽

...

Keyword(s):

Cerebral Palsy ◽

Executive Function ◽

White Matter ◽

Intelligence Quotient ◽

White Matter Integrity

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Abstract P366: High Burden of Tract-Specific White Matter Hyperintensities Relates to Impaired Microstructural Integrity of Distal White Matter Tracts in Community-Dwelling Elders

Stroke ◽

10.1161/str.52.suppl_1.p366 ◽

2021 ◽

Vol 52 (Suppl_1) ◽

Author(s):

YANPENG LIU ◽

YIWEI XIA ◽

XIAOXIAO WANG ◽

YI WANG ◽

LUMENG YANG ◽

...

Keyword(s):

Executive Function ◽

White Matter ◽

Cognitive Dysfunction ◽

White Matter Hyperintensities ◽

Brain Mri ◽

Mean Diffusivity ◽

Community Dwelling ◽

Superior Longitudinal Fasciculus ◽

High Burden ◽

Microstructural Integrity

Background and purpose: White matter hyperintensities (WMH) are common in elderly individuals and contribute to age-related cognitive dysfunction. Converging evidence indicates that WMH affect white matter (WM) microstructural integrity in WMH and their penumbra. We aimed to investigate whether this effect extends to the distal WM tracts, and to examine the association between distal WM microstructural integrity and cognitive dysfunction in community-dwelling elderly people. Methods: Brain MRI data including FLAIR and DTI sequences of 174 participants (74 ± 5 years) of the Shanghai Aging Study (SAS) were collected and analyzed. For each participant, WMH lesions were segmented automatically. Eighteen major WM tracts were reconstructed using automated quantitative tractography, and the mean diffusivity (MD) of distal WM tracts (excluding an area of 12 mm around the WMH) was calculated. Multivariable linear regression was performed. Results: A high burden of tract-specific WMH was related to a high MD of distal WM tracts in the forceps major (FMA), anterior thalamic radiations (ATR), cingulum cingulate gyrus (CCG), corticospinal tract (CST), superior longitudinal fasciculus-parietal (SLFP), superior longitudinal fasciculus-temporal (SLFT), and uncinate fasciculus (UNC). Furthermore, a high MD of distal tracts was linked to worse attention and executive function in the forceps minor (FMI), right CCG, left inferior longitudinal fasciculus (ILF), SLFP, SLFT and UNC. Conclusions: The effect of WMH on the microstructural integrity of WM tracts may propagate along tracts to distal regions farther than the penumbra and eventually might affect attention and executive function.

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P4-033: THE ASSOCIATION OF PERIVENTRICULAR WHITE MATTER LESION VOLUME WITH GLOBAL COGNITION, EXECUTIVE FUNCTION, GAIT SPEED AND PULSE WAVE VELOCITY

Alzheimer s & Dementia ◽

10.1016/j.jalz.2018.06.2435 ◽

2006 ◽

Vol 14 (7S_Part_27) ◽

pp. P1445-P1446 ◽

Cited By ~ 1

Author(s):

Walid Ahmed Al Keridy ◽

Ging-Yuek Robin Hsiung ◽

John R. Best ◽

Teresa Liu-Ambrose

Keyword(s):

Executive Function ◽

White Matter ◽

Pulse Wave Velocity ◽

Wave Velocity ◽

Gait Speed ◽

Pulse Wave ◽

White Matter Lesion ◽

Periventricular White Matter ◽

Lesion Volume ◽

Global Cognition

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Structural integrity of white matter tracts as a predictor of acute ischemic stroke outcome

International Journal of Stroke ◽

10.1177/1747493020915251 ◽

2020 ◽

Vol 15 (9) ◽

pp. 965-972

Author(s):

Deepthi Rajashekar ◽

Pauline Mouchès ◽

Jens Fiehler ◽

Bijoy K Menon ◽

Mayank Goyal ◽

...

Keyword(s):

Ischemic Stroke ◽

White Matter ◽

Acute Ischemic Stroke ◽

Support Vector Regression ◽

Support Vector ◽

Stroke Severity ◽

Lesion Volume ◽

White Matter Tract ◽

Support Vector Regression Model ◽

White Matter Tracts

Background and purpose Clinical assessment scores in acute ischemic stroke are only moderately correlated with lesion volume since lesion location is an important confounding factor. Many studies have investigated gray matter indicators of stroke severity, but the understanding of white matter tract involvement is limited in the early phase after stroke. This study aimed to measure and model the involvement of white matter tracts with respect to 24-h post-stroke National Institutes of Health Stroke Scale (NIHSS). Material and methods A total of 96 patients (50 females, mean age 66.4 ± 14.0 years, median NIHSS 5, interquartile range: 2–9.5) with follow-up fluid-attenuated inversion recovery magnetic resonance imaging data sets acquired one to seven days after acute ischemic stroke onset due to proximal anterior circulation occlusion were included. Lesions were semi-automatically segmented and non-linearly registered to a common reference atlas. The lesion overlap and tract integrity were determined for each white matter tract in the AALCAT atlas and used to model NIHSS outcomes using a supervised linear-kernel support vector regression method, which was evaluated using leave-one-patient-out cross validation. Results The support vector regression model using the tract integrity and tract lesion overlap measurements predicted the 24-h NIHSS score with a high correlation value of r = 0.7. Using the tract overlap and tract integrity feature improved the modeling accuracy of NIHSS significantly by 6% (p < 0.05) compared to using overlap measures only. Conclusion White matter tract integrity and lesion load are important predictors for clinical outcome after an acute ischemic stroke as measured by the NIHSS and should be integrated for predictive modeling.

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Long-term cerebral white and gray matter changes after preeclampsia

Neurology ◽

10.1212/wnl.0000000000003765 ◽

2017 ◽

Vol 88 (13) ◽

pp. 1256-1264 ◽

Cited By ~ 30

Author(s):

Timo Siepmann ◽

Henry Boardman ◽

Amy Bilderbeck ◽

Ludovica Griffanti ◽

Yvonne Kenworthy ◽

...

Keyword(s):

Cardiovascular Risk ◽

White Matter ◽

Temporal Lobe ◽

Gray Matter ◽

Diffusion Tensor ◽

Brain Mri ◽

Risk Profile ◽

Lesion Volume ◽

Cardiovascular Risk Profile ◽

Microstructural Integrity

Objective:To determine whether changes in cerebral structure are present after preeclampsia that may explain increased cerebrovascular risk in these women.Methods:We conducted a case control study in women between 5 and 15 years after either a preeclamptic or normotensive pregnancy. Brain MRI was performed. Analysis of white matter structure was undertaken using voxel-based segmentation of fluid-attenuation inversion recovery sequences to assess white matter lesion volume and diffusion tensor imaging to measure microstructural integrity. Voxel-based analysis of gray matter volumes was performed with adjustment for skull size.Results:Thirty-four previously preeclamptic women (aged 42.8 ± 5.1 years) and 49 controls were included. Previously preeclamptic women had reduced cortical gray matter volume (523.2 ± 30.1 vs 544.4 ± 44.7 mL, p < 0.05) and, although both groups displayed white matter lesions, changes were more extensive in previously preeclamptic women. They displayed increased temporal lobe white matter disease (lesion volume: 23.2 ± 24.9 vs 10.9 ± 15.0 μL, p < 0.05) and altered microstructural integrity (radial diffusivity: 538 ± 19 vs 526 ± 18 × 10−6 mm2/s, p < 0.01), which also extended to occipital and parietal lobes. The degree of temporal lobe white matter change in previously preeclamptic women was independent of their current cardiovascular risk profile (p < 0.05) and increased with time from index pregnancy (p < 0.05).Conclusion:A history of preeclampsia is associated with temporal lobe white matter changes and reduced cortical volume in young women, which is out of proportion to their classic cardiovascular risk profile. The severity of changes is proportional to time since pregnancy, which would be consistent with continued accumulation of damage after pregnancy.

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