White matter hyperintensities and cognitive reserve during a working memory task: a functional magnetic resonance imaging study in cognitively normal older adults

Fernández-Cabello, Sara; Valls-Pedret, Cinta; Schurz, Matthias; Vidal-Piñeiro, Dídac; Sala‐Llonch, Roser; Bargalló, Núria; Ros, Emilio; Bartrés‐Faz, David

doi:10.1016/j.neurobiolaging.2016.08.008

Cited by 26 publications

(20 citation statements)

References 62 publications

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“…This effect has been shown to be, at least partly, driven by cognitive reserve (Scarmeas et al, 2003; Steffener et al, 2009; Brickman et al, 2011; Tucker and Stern, 2011; Stern, 2012; Stern et al, 2012; Fernandez-Cabello et al, 2016). Moreover, our results argue for a distinct and selective association between “specific” (here defined by PD pathology) and “unspecific” (age-related) brain pathologies and WMC-related gait and executive function deficits.…”

Section: Discussionmentioning

confidence: 99%

White Matter Changes-Related Gait and Executive Function Deficits: Associations with Age and Parkinson's Disease

Sartor

Bettecken

Bernhard

et al. 2017

Front. Aging Neurosci.

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Background: White matter changes (WMC) are a common finding among older adults and patients with Parkinson's disease (PD), and have been associated with, e.g., gait deficits and executive dysfunction. How the factors age and PD influence WMC-related deficits is, to our best knowledge, not investigated to date. We hypothesized that advanced age and presence of PD leads to WMC-related symptoms while practicing tasks with a low complexity level, and low age and absence of PD leads to WMC-related symptoms while practicing tasks with a high complexity level.Methods: Hundred and thirty-eight participants [65 young persons without PD (50–69 years, yPn), 22 young PD patients (50–69 years, yPD), 36 old persons without PD (70–89 years, oPn) and 15 old PD patients (70–89 years, oPD)] were included. Presence and severity of WMC were determined with the modified Fazekas score. Velocity of walking under single and dual tasking conditions and the Trail Making Test (TMT) were used as gait and executive function parameters. Correlations between presence and severity of WMC, and gait and executive function parameters were tested in yPn, yPD, oPn, and oPD using Spearman's rank correlation, and significance between groups was evaluated with Fisher's z-transformed correlation coefficient.Results: yPn and yPD, as well as oPn and oPD did not differ regarding demographic and clinical parameters. Severity of WMC was not significantly different between groups. yPn and yPD displayed significant correlations of WMC with executive function parameters at low levels of task complexity, oPn at intermediate, and oPD at high complexity levels.Conclusion: This study argues for a relevant association of age and PD-related brain pathology with WMC-related gait and executive function deficits.

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Section: Discussionmentioning

confidence: 99%

White Matter Changes-Related Gait and Executive Function Deficits: Associations with Age and Parkinson's Disease

Sartor

Bettecken

Bernhard

et al. 2017

Front. Aging Neurosci.

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“…White matter hyperintensities (WMH), or leukoaraiosis, is a condition routinely found in brain magnetic resonance imaging (MRI) scans of older people and contributes to cognitive and functional decline (Fernández-Cabello et al, 2016;Haynes et al, 2017;Ritchie et al, 2015b). These lesions appear as hyperintensities in the white matter (WM) on T2-weighted (T2W) or fluid attenuated inversion recovery (FLAIR) MRI, and have been described as WM degeneration characterized by axonal loss, demyelination and gliosis, on neuropathological examination (Fazekas et al, 1993).…”

Section: Introductionmentioning

confidence: 99%

Spatial Gradient of Microstructural Changes in Normal-Appearing White Matter in Tracts Affected by White Matter Hyperintensities in Older Age

Maniega

Meijboom

Chappell

et al. 2018

Preprint

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Brain white matter hyperintensities (WMH), common in older adults, may contribute to cortical disconnection and cognitive dysfunction. The presence of WMH within white matter (WM) tracts indicates underlying microstructural WM changes that may also affect the normal-appearing WM (NAWM) of a tract. We performed an exploratory study using diffusion magnetic resonance imaging of 52 healthy participants from the Lothian Birth Cohort 1936 (age 72.2 ± 0.7 years) selected to include a range of WMH burden, to quantify microstructural changes of tracts intersecting WMH. We reconstructed tracts using automated tractography and identified intersections with WMH. Tissue volumes and water diffusion tensor parameters (mean diffusivity (MD) and fractional anisotropy (FA)) were established for tract-WMH and tract-NAWM. MD and FA were also measured for tract-NAWM at 2 mm incremental distances from the tract-WMH edge, and from the edge of nearby, non-intersecting, WMH. We observed microstructural changes in tract-WMH suggestive of tissue damage. Tract-NAWM also showed a spatial gradient of FA and MD abnormalities, which diminished with distance from the tract-WMH. Nearby WMH lesions, not directly crossed by the tract, also affected tract microstructure with a similar pattern. Additionally, both FA and MD changes in tract-NAWM were predicted by FA and MD changes respectively in tract-WMH. FA was also predicted by tract-WMH overlap volume, whereas MD was better predicted by whole-brain WMH load. These results suggest that tract-NAWM microstructure is affected by the pathological process underlying WMH, when WMH are either within or near to the tract. The changes in NAWM tract tissue may indicate future lesion progression and may play an important role in cognitive ageing.

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“…The present study draws from a previous investigation by our group and is based on its fMRI findings. In the stated report, we observed that older adults can engage distinct brain activity patterns to successfully solve a particular working memory paradigm (see Fernández-Cabello et al, 2016 for further details). In the present study, two real tDCS conditions were designed based on those previous fMRI findings, to induce two distinct electric field distribution patterns, which were expected to produce either generalized cortical overactivity (i.e., condition 1, or C1) or an antero-posterior dissociation aiming to enhance frontal areas whereas reducing the posteromedial cortex activity (i.e., condition 2, or C2; see section 2.4 for detailed information).…”

Section: Introductionmentioning

confidence: 88%

“…As mentioned, the weighted target ! -maps used in this study were designed based on the findings obtained in our previous fMRI study (Fernández-Cabello et al 2016). More precisely, on the one hand, the C1 montage was grounded on an fMRI pattern of extended cortical activity, including the bilateral middle frontal gyri, the paracingulate gyri, the precuneus cortex, the bilateral supramarginal gyri and/or intraparietal sulcus area and the lingual gyri ( Fig.…”

Section: Tdcs Parametersmentioning

confidence: 99%

Multifocal tDCS modulates resting-state functional connectivity in older adults depending on induced electric field and baseline connectivity

Abellaneda‐Pérez

Vaqué‐Alcázar

Perellón‐Alfonso

et al. 2020

Preprint

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Background. Advancing age affects the brain's resting-state functional networks. Combining non-invasive brain stimulation (NIBS) with neuroimaging is a promising approach to modulate activity across resting-state functional systems and explore their true contribution to cognitive function in aging. However, substantial individual variability in the response to NIBS has been reported and, hence, identifying the individual predictors of NIBS-induced modulatory effects is crucial if we are to harness their potential.Methods. Thirty-one cognitively healthy older adults (71.68 ± 2.5 years; 19 females) underwent two different multifocal real tDCS conditions (C1 and C2) and a sham condition in a crossover design during a resting-state functional magnetic resonance imaging (rs-fMRI) acquisition. The real tDCS conditions were designed to induce two distinct electric field distribution patterns either targeting generalized cortical overactivity or a dissociation between the frontal areas and the posteromedial cortex. Stimulation was delivered through an MRI-compatible device using 8 small circular electrodes. Each individuals' anatomical T1-weighted MRI was used to generate a finite element model to define the individual electric field generated by each tDCS condition.Results. The two tDCS conditions modulated resting-state connectivity differently. C1 increased the coactivation of numerous functional couplings as compared to sham, however, a smaller amount of connections increased in C1 as compared to C2, while no differences between C2 and sham were appreciated. At the group level, C1-induced modulations primarily included temporo-occipital areas and distinct cerebellar regions. This functional pattern was anatomically consistent with the estimated distribution of the induced electric field in the C1 condition. Finally, at the individual level, the extent of tDCS-induced rs-fMRI modulation in C1 was predicted by baseline resting-state connectivity and simulation-based electric field magnitude. Discussion.Our results highlighted that multifocal tDCS procedures can effectively change neural dynamics in the elderly consistently with the spatial distribution of the estimated electric fields on the brain. Furthermore, we showed that specific brain factors that have been revealed to explain part of the individual variability to NIBS in young samples are also relevant in older adults. In accordance, designing multifocal tDCS configurations based on specific fMRI patterns appears to be a valuable approach to precisely adjust those complex neural dynamics sustaining cognition that are affected as a function of age. Furthermore, these innovative NIBS-based interventions should be individually-tailored based on subject-specific structural and functional data to ultimately boost their potential in aged populations. KeywordsAging, electrical modeling, finite element method, multifocal transcranial direct current stimulation, resting-state functional magnetic resonance imaging.

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White matter hyperintensities and cognitive reserve during a working memory task: a functional magnetic resonance imaging study in cognitively normal older adults

Cited by 26 publications

References 62 publications

White Matter Changes-Related Gait and Executive Function Deficits: Associations with Age and Parkinson's Disease

White Matter Changes-Related Gait and Executive Function Deficits: Associations with Age and Parkinson's Disease

Spatial Gradient of Microstructural Changes in Normal-Appearing White Matter in Tracts Affected by White Matter Hyperintensities in Older Age

Multifocal tDCS modulates resting-state functional connectivity in older adults depending on induced electric field and baseline connectivity

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