Dataset Information

White matter hyperintensities among older adults are associated with futile increase in frontal activation and functional connectivity during spatial search.

ABSTRACT: The mechanisms by which aging and other processes can affect the structure and function of brain networks are important to understanding normal age-related cognitive decline. Advancing age is known to be associated with various disease processes, including clinically asymptomatic vascular and inflammation processes that contribute to white matter structural alteration and potential injury. The effects of these processes on the function of distributed cognitive networks, however, are poorly understood. We hypothesized that the extent of magnetic resonance imaging white matter hyperintensities would be associated with visual attentional control in healthy aging, measured using a functional magnetic resonance imaging search task. We assessed cognitively healthy older adults with search tasks indexing processing speed and attentional control. Expanding upon previous research, older adults demonstrate activation across a frontal-parietal attentional control network. Further, greater white matter hyperintensity volume was associated with increased activation of a frontal network node independent of chronological age. Also consistent with previous research, greater white matter hyperintensity volume was associated with anatomically specific reductions in functional magnetic resonance imaging functional connectivity during search among attentional control regions. White matter hyperintensities may lead to subtle attentional network dysfunction, potentially through impaired frontal-parietal and frontal interhemispheric connectivity, suggesting that clinically silent white matter biomarkers of vascular and inflammatory injury can contribute to differences in search performance and brain function in aging, and likely contribute to advanced age-related impairments in cognitive control.

SUBMITTER: Lockhart SN

PROVIDER: S-EPMC4368687 | biostudies-literature | 2015

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

White matter hyperintensities among older adults are associated with futile increase in frontal activation and functional connectivity during spatial search.

Lockhart Samuel N SN Luck Steven J SJ Geng Joy J Beckett Laurel L Disbrow Elizabeth A EA Carmichael Owen O DeCarli Charles C

PloS one 20150320 3

The mechanisms by which aging and other processes can affect the structure and function of brain networks are important to understanding normal age-related cognitive decline. Advancing age is known to be associated with various disease processes, including clinically asymptomatic vascular and inflammation processes that contribute to white matter structural alteration and potential injury. The effects of these processes on the function of distributed cognitive networks, however, are poorly under ...[more]

PMID: 25793922

Similar Datasets

Project description:Frontal lobe structures decline faster than most other brain regions in older adults. Age-related change in the frontal lobe is associated with poorer executive function (e.g., working memory, switching/set-shifting, and inhibitory control). The effects and presence of frontal lobe white matter hyperintensities (WMH) on executive function in normal aging is relatively unknown. The current study assessed relationships between region-specific frontal WMH load and cognitive performance in healthy older adults using three executive function tasks from the NIH Toolbox (NIHTB) Cognition Battery. A cohort of 279 healthy older adults ages 65-88 completed NIHTB and 3T T1-weighted and FLAIR MRI. Lesion Segmentation Toolbox quantified WMH volume and generated lesion probability maps. Individual lesion maps were registered to the Desikan-Killiany atlas in FreeSurfer 6.0 to define regions of interest (ROI). Independent linear regressions assessed relationships between executive function performance and region-specific WMH in frontal lobe ROIs. All models included age, sex, education, estimated total intracranial volume, multi-site scanner differences, and cardiovascular disease risk using Framingham criteria as covariates. Poorer set-shifting performance was associated with greater WMH load in three frontal ROIs including bilateral superior frontal (left β = -0.18, FDR-p = 0.02; right β = -0.20, FDR-p = 0.01) and right medial orbitofrontal (β = -0.17, FDR-p = 0.02). Poorer inhibitory performance associated with higher WMH load in one frontal ROI, the right superior frontal (right β = -0.21, FDR-p = 0.01). There were no significant associations between working memory and WMH in frontal ROIs. Our study demonstrates that location and pattern of frontal WMH may be important to assess when examining age-related differences in cognitive functions involving switching/set-shifting and inhibition. On the other hand, working memory performance was not related to presence of frontal WMH in this sample. These data suggest that WMH may contribute selectively to age-related declines in executive function. Findings emerged beyond predictors known to be associated with WMH presence, including age and cardiovascular disease risk. The spread of WMH within the frontal lobes may play a key role in the neuropsychological profile of cognitive aging. Further research should explore whether early intervention on modifiable vascular factors or cognitive interventions targeted for executive abilities may help mitigate the effect of frontal WMH on executive function.

Project description:Background and Purpose: White matter hyperintensities (WMH) are commonly seen on structural MRI of older adults and are a manifestation of underlying and adjacent tissue damage. WMH may contribute to cortical disconnection and cognitive dysfunction, but it is unclear how WMH affect intersecting or nearby white matter tract integrity. This study investigated the effects of WMH on tract microstructure by determining the spatial distribution of water diffusion characteristics in white matter tract areas adjacent to both intersecting and nearby WMH. Methods: We used diffusion and structural MRI data from 52 representative participants from the Lothian Birth Cohort 1936 (72.2 ± 0.7 years) including a range of WMH burden. We segmented WMH, reconstructed 18 main white mater tracts using automated quantitative tractography and identified intersections between tracts and WMH. We measured mean diffusivity (MD) and fractional anisotropy (FA) in tract tissue at 2 mm incremental distances from tract-intersecting and non-intersecting (nearby) WMH. Results: We observed a spatial gradient of FA and MD abnormalities for most white matter tracts which diminished with a similar distance pattern for tract-intersecting and nearby WMH. Overall, FA was higher, while MD was lower around nearby WMH compared with tract-intersecting WMH. However, for some tracts, FA was lower in areas immediately surrounding nearby WMH, although with faster normalization than in FA values surrounding tract-intersecting WMH. Conclusion: WMH have similar effects on tract infrastructure, whether they be intersecting or nearby. However, the observed differences in tract water diffusion properties around WMH suggest that degenerative processes in small vessel disease may propagate further along the tract for intersecting WMH, while in some areas of the brain there is a larger and more localized accumulation of axonal damage in tract tissue nearby a non-connected WMH. Longitudinal studies should address differential effects of intersecting vs. nearby WMH progression and how they contribute to cognitive aging.

Project description:BackgroundWhite matter hyperintensities are an important marker of cerebral small vessel disease. This disease burden is commonly described as hyperintense areas in the cerebral white matter, as seen on T2-weighted fluid attenuated inversion recovery magnetic resonance imaging data. Studies have demonstrated associations with various cognitive impairments, neurological diseases, and neuropathologies, as well as clinical and risk factors, such as age, sex, and hypertension. Due to their heterogeneous appearance in location and size, studies have started to investigate spatial distributions and patterns, beyond summarizing this cerebrovascular disease burden in a single metric-its volume. Here, we review the evidence of association of white matter hyperintensity spatial patterns with its risk factors and clinical diagnoses.Design/methodsWe performed a systematic review in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) Statement. We used the standards for reporting vascular changes on neuroimaging criteria to construct a search string for literature search on PubMed. Studies written in English from the earliest records available until January 31st, 2023, were eligible for inclusion if they reported on spatial patterns of white matter hyperintensities of presumed vascular origin.ResultsA total of 380 studies were identified by the initial literature search, of which 41 studies satisfied the inclusion criteria. These studies included cohorts based on mild cognitive impairment (15/41), Alzheimer's disease (14/41), Dementia (5/41), Parkinson's disease (3/41), and subjective cognitive decline (2/41). Additionally, 6 of 41 studies investigated cognitively normal, older cohorts, two of which were population-based, or other clinical findings such as acute ischemic stroke or reduced cardiac output. Cohorts ranged from 32 to 882 patients/participants [median cohort size 191.5 and 51.6% female (range: 17.9-81.3%)]. The studies included in this review have identified spatial heterogeneity of WMHs with various impairments, diseases, and pathologies as well as with sex and (cerebro)vascular risk factors.ConclusionThe results show that studying white matter hyperintensities on a more granular level might give a deeper understanding of the underlying neuropathology and their effects. This motivates further studies examining the spatial patterns of white matter hyperintensities.

Project description:White matter hyperintensities as seen on brain T2-weighted magnetic resonance imaging are associated with varying degrees of cognitive dysfunction in stroke, cerebral small vessel disease and dementia. The pathophysiological mechanisms within the white matter accounting for cognitive dysfunction remain unclear. With the hypothesis that gliovascular interactions are impaired in subjects with high burdens of white matter hyperintensities, we performed clinicopathological studies in post-stroke survivors, who had exhibited greater frontal white matter hyperintensities volumes that predicted shorter time to dementia onset. Histopathological methods were used to identify substrates in the white matter that would distinguish post-stroke demented from post-stroke non-demented subjects. We focused on the reactive cell marker glial fibrillary acidic protein (GFAP) to study the incidence and location of clasmatodendrosis, a morphological attribute of irreversibly injured astrocytes. In contrast to normal appearing GFAP+ astrocytes, clasmatodendrocytes were swollen and had vacuolated cell bodies. Other markers such as aldehyde dehydrogenase 1 family, member L1 (ALDH1L1) showed cytoplasmic disintegration of the astrocytes. Total GFAP+ cells in both the frontal and temporal white matter were not greater in post-stroke demented versus post-stroke non-demented subjects. However, the percentage of clasmatodendrocytes was increased by >2-fold in subjects with post-stroke demented compared to post-stroke non-demented subjects (P = 0.026) and by 11-fold in older controls versus young controls (P < 0.023) in the frontal white matter. High ratios of clasmotodendrocytes to total astrocytes in the frontal white matter were consistent with lower Mini-Mental State Examination and the revised Cambridge Cognition Examination scores in post-stroke demented subjects. Double immunofluorescent staining showed aberrant co-localization of aquaporin 4 (AQP4) in retracted GFAP+ astrocytes with disrupted end-feet juxtaposed to microvessels. To explore whether this was associated with the disrupted gliovascular interactions or blood-brain barrier damage, we assessed the co-localization of GFAP and AQP4 immunoreactivities in post-mortem brains from adult baboons with cerebral hypoperfusive injury, induced by occlusion of three major vessels supplying blood to the brain. Analysis of the frontal white matter in perfused brains from the animals surviving 1-28 days after occlusion revealed that the highest intensity of fibrinogen immunoreactivity was at 14 days. At this survival time point, we also noted strikingly similar redistribution of AQP4 and GFAP+ astrocytes transformed into clasmatodendrocytes. Our findings suggest novel associations between irreversible astrocyte injury and disruption of gliovascular interactions at the blood-brain barrier in the frontal white matter and cognitive impairment in elderly post-stroke survivors. We propose that clasmatodendrosis is another pathological substrate, linked to white matter hyperintensities and frontal white matter changes, which may contribute to post-stroke or small vessel disease dementia.

Dataset Information

White matter hyperintensities among older adults are associated with futile increase in frontal activation and functional connectivity during spatial search.

Publications

White matter hyperintensities among older adults are associated with futile increase in frontal activation and functional connectivity during spatial search.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets