The Impact of Strategic White Matter Hyperintensity Lesion Location on Language

doi:10.1016/j.jagp.2020.06.009

The American Journal of Geriatric Psychiatry

Volume 29, Issue 2, February 2021, Pages 156-165

https://doi.org/10.1016/j.jagp.2020.06.009 Get rights and content

Highlights

•
Is there an association between white matter hyperintensities lesion location and language?
•
In this cross-sectional analysis of a population-based study that included 819 persons, the left cingulum of the cingulate gyrus was identified as a strategic white matter tract for the Modified Boston Naming Test.
•
The language performance is sensitive to ischemic damage in a larger subcortical network than was previously thought.

ABSTRACT

Objective

The impact of white matter hyperintensities (WMH) on language possibly depends on lesion location through disturbance of strategic white matter tracts. We examined the impact of WMH location on language in elderly Asians.

Design

Cross-sectional.

Setting

Population-based.

Participants

Eight-hundred nineteen residents of Singapore, ages (≥65 years).

Measurements

Clinical, cognitive and 3T magnetic resonance imaging assessments were performed on all participants. Language was assessed using the Modified Boston Naming Test (MBNT) and Verbal Fluency (VF). Hypothesis-free region-of-interest-based (ROI) analyses based on major white matter tracts were used to determine the association between WMH location and language. Conditional dependencies between the regional WMH volumes and language were examined using Bayesian-network analysis.

Results

ROI-based analyses showed that WMH located within the anterior thalamic radiation (mean difference: −0.12, 95% confidence interval [CI]: −0.22; −0.02, p = 0.019) and uncinate fasciculus (mean difference: −0.09, 95% CI: −0.18; −0.01, p = 0.022) in the left hemisphere were significantly associated with worse VF but did not survive multiple testing. Conversely, WMH volume in the left cingulum of cingulate gyrus was significantly associated with MBNT performance (mean difference: −0.09, 95% CI: −0.17; −0.02, p = 0.016). Bayesian-network analyses confirmed the left cingulum of cingulate gyrus as a direct determinant of MBNT performance.

Conclusion

Our findings identify the left cingulum of cingulate gyrus as a strategic white matter tract for MBNT, suggesting that language – is sensitive to subcortical ischemic damage. Future studies on the role of sporadic ischemic lesions and vascular cognitive impairment should not only focus on total WMH volume but should also take WMH lesion location into account when addressing language.

Section snippets

INTRODUCTION

Neuropsychological assessment plays a crucial role in detecting loss of cognitive functions and change in behavioral and functional state due to disruption in different neural networks and subnetworks caused by vascular damage.¹ Neuropsychological tests include tasks assessing domains considered to reflect “cortical function” for example, language and visuoconstruction and tasks that tap into domains that are especially sensitive to vascular damage in subcortical regions such as attention and

Study Sample

The Epidemiology of Dementia In Singapore (EDIS) is a subsample of the Singapore Epidemiology of Eye Disease (SEED) study, a large population-based study of three major ethnic cohorts: Chinese (Singapore Chinese Eye Study [SCES]), Malay (Singapore Malay Eye Study [SiMES-2]), and Indians (Singapore Indian Eye Study [SINDI-2]).¹⁰ A similar protocol was employed for recruitment and assessment of study participants for all the three ethnicities. As part of the first phase of the EDIS study,

RESULTS

Characteristics of the study population are shown in Table 1. The mean age of the participants was 70.2 years and 54% were women. The median WMH was 2.33 mL and the prevalence of lacunes in this sample was 17%. Chinese performed better on language domain and MBNT whereas Malay and Indian had lower scores on language domain and MBNT (Table 2); no differences in VF performance were found among the three ethnicities.

DISCUSSION

This study identified strategic white matter tracts in which WMH are associated with worse performance in language in a population-based setting. More specifically, the left cingulum of the cingulate gyrus was identified as a strategic white matter tract for the MBNT. This suggests that the language is sensitive to ischemic damage in a larger subcortical network than was previously thought.

Previous studies have shown that the total WMH volume only explains a limited proportion of

CONCLUSION

This study demonstrated an association between WMH in the left cingulum and the MBNT. Our findings support the concept that WMH located in these strategic white matter tracts specifically left cingulum disrupt language and suggest that the subcortical network involved in language production is larger than was previously thought. Future studies on the role of sporadic ischemic lesions and vascular cognitive impairment should not only focus on total WMH volume but should also take WMH lesion

AUTHOR CONTRIBUTIONS

Saima Hilal: Conceptualization, Methodology, Formal analysis, Writing- Original draft preparation, Project administration, Funding acquisition. J. Matthijs Biesbroek: Conceptualization, Methodology, Formal analysis, Writing - Review & Editing. Henri Vrooman: Software, Methodology, Formal analysis. Eddie Chong: Methodology, Writing- Reviewing and Editing. Hugo J. Kuijf: Software, Methodology, Formal analysis. NarayanaswamyVenketasubramanian: Supervision. Ching-Yu Cheng: Supervision. Tien Yin

Disclosure

EDIS is supported by the National Medical Research Council (NMRC), Singapore (NMRC/CG/NUHS/2010 [Grant no: R-184-006-184-511]) and (NMRC/CSA/038/2013). Dr. Biessels is supported by Vici Grant 918.16.616 from ZonMw, The Netherlands. This work is additionally supported by bright focus foundation (reference no. A2018165F) [Grant no: R-608-000-248-597] awarded to Dr. Hilal.

Dr. Hilal received travel grant from Internationale Stichting Alzheimer Onderzoek (ISAO), the Netherlands. For the remaining

References (31)

JW Faulkner et al.
Mapping eloquent cortex: a voxel-based lesion-symptom mapping study of core speech production capacities in brain tumour patients
Brain Lang
(2020)
J Jiang et al.
The association of regional white matter lesions with cognition in a community-based cohort of older individuals
NeuroimageClin
(2018)
JM Wardlaw et al.
Neuroimaging standards for research into small vessel disease and its contribution to ageing and neurodegeneration
Lancet Neurol
(2013)
HA Vrooman et al.
Multi-spectral brain tissue segmentation using automatically trained k-nearest-neighbor classification
Neuroimage
(2007)
K Hua et al.
Tract probability maps in stereotaxic spaces: analyses of white matter anatomy and tract-specific quantification
Neuroimage
(2008)
M Duering et al.
Identification of a strategic brain network underlying processing speed deficits in vascular cognitive impairment
Neuroimage
(2013)
EJ Bubb et al.
The cingulum bundle: anatomy, function, and dysfunction
Neurosci Biobehav Rev
(2018)
P Battista et al.
Optimizing neuropsychological assessments for cognitive, behavioral, and functional impairment classification: machine learning study
Behav Neurol
(2017)
NF Dronkers et al.
Paul Broca's historic cases: high resolution MR imaging of the brains of leborgne and lelong
Brain
(2007)
M Duering et al.
Strategic role of frontal white matter tracts in vascular cognitive impairment: a voxel-based lesion-symptom mapping study in CADASIL
Brain
(2011)

JM Biesbroek et al.

Association between subcortical vascular lesion location and cognition: a voxel-based and tract-based lesion-symptom mapping study. The SMART-MR study

PloS One

(2013)

JM Biesbroek et al.

Impact of strategically located white matter hyperintensities on cognition in memory clinic patients with small vessel disease

PloS One

(2016)

JM Biesbroek et al.

Lesion location and cognitive impact of cerebral small vessel disease

Clin Sci

(2017)

K Kantarci et al.

Diffusion tensor imaging and cognitive function in older adults with no dementia

Neurology

(2011)

S Hilal et al.

Cortical cerebral microinfarcts on 3T MRI: a novel marker of cerebrovascular disease

Neurology

(2016)

Cited by (10)

Brain Structural Network Connectivity of Formal Thought Disorder Dimensions in Affective and Psychotic Disorders
2024, Biological Psychiatry
The psychopathological syndrome of formal thought disorder (FTD) is not only present in schizophrenia (SZ), but also highly prevalent in major depressive disorder and bipolar disorder. It remains unknown how alterations in the structural white matter connectome of the brain correlate with psychopathological FTD dimensions across affective and psychotic disorders.
Using FTD items of the Scale for the Assessment of Positive Symptoms and Scale for the Assessment of Negative Symptoms, we performed exploratory and confirmatory factor analyses in 864 patients with major depressive disorder (n = 689), bipolar disorder (n = 108), or SZ (n = 67) to identify psychopathological FTD dimensions. We used T1- and diffusion-weighted magnetic resonance imaging to reconstruct the structural connectome of the brain. To investigate the association of FTD subdimensions and global structural connectome measures, we employed linear regression models. We used network-based statistic to identify subnetworks of white matter fiber tracts associated with FTD symptomatology.
Three psychopathological FTD dimensions were delineated, i.e., disorganization, emptiness, and incoherence. Disorganization and incoherence were associated with global dysconnectivity. Network-based statistics identified subnetworks associated with the FTD dimensions disorganization and emptiness but not with the FTD dimension incoherence. Post hoc analyses on subnetworks did not reveal diagnosis × FTD dimension interaction effects. Results remained stable after correcting for medication and disease severity. Confirmatory analyses showed a substantial overlap of nodes from both subnetworks with cortical brain regions previously associated with FTD in SZ.
We demonstrated white matter subnetwork dysconnectivity in major depressive disorder, bipolar disorder, and SZ associated with FTD dimensions that predominantly comprise brain regions implicated in speech. Results open an avenue for transdiagnostic, psychopathology-informed, dimensional studies in pathogenetic research.
Association of white matter hyperintensity accumulation with domain-specific cognitive decline: a population-based cohort study
2023, Neurobiology of Aging
We investigated the association of load and accumulation of white matter hyperintensities (WMHs) with rate of cognitive decline. This population-based study included 510 dementia-free people (age ≥60 years) who had repeated measures of global and regional (lobar, deep, periventricular) WMHs up to 6 years (from 2001–2003 to 2007–2010) and repeated measures of cognitive function (episodic memory, semantic memory, category fluency, letter fluency, executive function, perceptual speed) up to 15 years (from 2001–2004 to 2016–2019). We found that greater baseline loads of global and regional WMHs were associated with faster decline in letter fluency, perceptual speed, and global cognition. Furthermore, faster accumulation of global, deep, and periventricular WMHs was related to accelerated cognitive decline, primarily in perceptual speed. These data show that WMHs are associated with decline in perceptual speed rather than episodic or semantic memory and that cognitive change is more vulnerable to WMH accumulations in deep and periventricular regions.
The volume and the distribution of premorbid white matter hyperintensities: Impact on post-stroke aphasia
2024, Human Brain Mapping
Structural Damage-Driven Brain Compensation in Near-Centenarians and Centenarians Without Dementia
2023, SSRN
Strategic white matter hyperintensity locations for cognitive impairment: A multicenter lesion-symptom mapping study in 3525 memory clinic patients
2023, Alzheimer's and Dementia
Analysis of Risk Factors for White Matter Hyperintensity in Older Adults without Stroke
2023, Brain Sciences

View all citing articles on Scopus

^a: SawSwee Hock School of Public Health, National University of Singapore, Tahir Foundation Building, 12 Science Drive 2, Singapore 117549.

View full text

Regular Research ArticleThe Impact of Strategic White Matter Hyperintensity Lesion Location on Language

Highlights

ABSTRACT

Objective

Design

Setting

Participants

Measurements

Results

Conclusion

Section snippets

INTRODUCTION

Study Sample

RESULTS

DISCUSSION

CONCLUSION

AUTHOR CONTRIBUTIONS

Disclosure

Brain Lang

NeuroimageClin

Lancet Neurol

Neuroimage

Neuroimage

Neuroimage

Neurosci Biobehav Rev

Optimizing neuropsychological assessments for cognitive, behavioral, and functional impairment classification: machine learning study

Behav Neurol

Paul Broca's historic cases: high resolution MR imaging of the brains of leborgne and lelong

Brain

Strategic role of frontal white matter tracts in vascular cognitive impairment: a voxel-based lesion-symptom mapping study in CADASIL

Brain

Association between subcortical vascular lesion location and cognition: a voxel-based and tract-based lesion-symptom mapping study. The SMART-MR study

PloS One

Impact of strategically located white matter hyperintensities on cognition in memory clinic patients with small vessel disease

PloS One

Lesion location and cognitive impact of cerebral small vessel disease

Clin Sci

Diffusion tensor imaging and cognitive function in older adults with no dementia

Neurology

Cortical cerebral microinfarcts on 3T MRI: a novel marker of cerebrovascular disease

Neurology

Regular Research Article
The Impact of Strategic White Matter Hyperintensity Lesion Location on Language