Clinically silent Alzheimer's and vascular pathologies influence brain networks supporting executive function in healthy older adults

Gold, Brian T.; Brown, Christopher; Hakun, Jonathan G.; Shaw, Leslie M.; Trojanowski, John Q.; Smith, Charles D.

doi:10.1016/j.neurobiolaging.2017.06.012

Cited by 15 publications

(9 citation statements)

References 68 publications

(78 reference statements)

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“…The WMH group had higher BOLD response compared to HYA during the executive contrast, which is consistent with other studies on executive function ( Gold et al, 2017 ) and spatial search tasks ( Lockhart et al, 2015 ; Gold et al, 2017 ), and is linked with white matter tract deterioration ( Madden et al, 2007 ; Persson et al, 2011 ). Unlike reports of frontal-network over-activation ( Lockhart et al, 2015 ; Gold et al, 2017 ), WMH atypically recruited highly vascularized areas of the precuneous and posterior cingulate. The precuneous, posterior cingulate cortex, and surrounding regions are a core feature of the default mode network ( McKiernan et al, 2003 ).…”

Section: Discussionsupporting

confidence: 91%

“…BOLD is a functional MRI (fMRI) approach which can probe CSVD by characterizing neurovascular signal patterns that may relate to impaired dorsal attention, default mode and fronto-parietal control networks ( Spreng et al, 2013 ). To date, however, task-based fMRI among adults with WMH has produced conflicting findings; both increased and decreased activation are reported in attentional neural networks ( Nordahl et al, 2006 ; Venkatraman et al, 2010 ; Hedden et al, 2012 ; Lockhart et al, 2015 ; Gold et al, 2017 ). Despite the utility of BOLD fMRI, challenges exist in the context of aging that influence signal-to-noise ratio and specificity of activation, be they physiological, neurovascular, or metabolic ( Huettel et al, 2001 ).…”

Section: Introductionmentioning

confidence: 99%

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Attention-Related Brain Activation Is Altered in Older Adults With White Matter Hyperintensities Using Multi-Echo fMRI

et al. 2018

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Cognitive decline is often undetectable in the early stages of accelerated vascular aging. Attentional processes are particularly affected in older adults with white matter hyperintensities (WMH), although specific neurovascular mechanisms have not been elucidated. We aimed to identify differences in attention-related neurofunctional activation and behavior between adults with and without WMH. Older adults with moderate to severe WMH (n = 18, mean age = 70 years), age-matched adults (n = 28, mean age = 72), and healthy younger adults (n = 19, mean age = 25) performed a modified flanker task during multi-echo blood oxygenation level dependent functional magnetic resonance imaging. Task-related activation was assessed using a weighted-echo approach. Healthy older adults had more widespread response and higher amplitude of activation compared to WMH adults in fronto-temporal and parietal cortices. Activation associated with processing speed was absent in the WMH group, suggesting attention-related activation deficits that may be a consequence of cerebral small vessel disease. WMH adults had greater executive contrast activation in the precuneous and posterior cingulate gyrus compared to HYA, despite no performance benefits, reinforcing the network dysfunction theory in WMH.

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Section: Discussionsupporting

confidence: 91%

Section: Introductionmentioning

confidence: 99%

Attention-Related Brain Activation Is Altered in Older Adults With White Matter Hyperintensities Using Multi-Echo fMRI

et al. 2018

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“…Interestingly, the LA-MCI and LA-VD groups in our study showed higher FC between the CEN and SN, especially in the bilateral dlPFC, ventrolateral PFC, bilateral SMA, and IPL. This may due to the changes in functional compensation in LA patients with cognitive dysfunction (Lockhart et al, 2015; Gold et al, 2017).…”

Section: Discussionmentioning

confidence: 99%

Abnormal Interactions of the Salience Network, Central Executive Network, and Default-Mode Network in Patients With Different Cognitive Impairment Loads Caused by Leukoaraiosis

Chen

Liu

et al. 2019

Front. Neural Circuits

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Leukoaraiosis (LA) is associated with cognitive impairment in the older people which can be demonstrated in functional connectivity (FC) based on resting-state functional magnetic resonance imaging (rs-fMRI). This study is to explore the FC changes in LA patients with different cognitive status by three network models. Fifty-three patients with LA were divided into three groups: the normal cognition (LA-NC; n = 14, six males), mild cognitive impairment (LA-MCI; n = 27, 13 males), and vascular dementia (LA-VD; n = 12, six males), according to the Mini Mental State Exam (MMSE) and Clinical Dementia Rating (CDR). The three groups and 30 matched healthy controls (HCs; 11 males) underwent rs-fMRI. The data of rs-fMRI were analyzed by independent components analysis (ICA) and region of interest (ROI) analysis by the REST toolbox. Then the FC was respectively analyzed by the default-mode network (DMN), salience networks (SNs) and the central executive network (CEN) with their results compared among the different groups. For inter-brain network analysis, there were negative FC between the SN and DMN in LA groups, and the FC decreased when compared with HC group. While there were enhanced inter-brain network FC between the SN and CEN as well as within the SN. The FC in patients with LA can be detected by different network models of rs-fMRI. The multi-model analysis is helpful for the further understanding of the cognitive changes in those patients.

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“…Another limitation is the lack of core AD biomarkers. Prior research suggested that WMH load might interact with the hallmarks of AD pathology, such as abnormal deposition of β‐amyloid (Aβ) (Gold et al, ) and tau‐protein (McAleese et al, ) in cognitively unimpaired participants. Therefore, the study of the impact of core AD pathology on the mediation effects here described represents an important topic for future research.…”

Section: Discussionmentioning

confidence: 99%

White matter hyperintensities mediate gray matter volume and processing speed relationship in cognitively unimpaired participants

Brugulat‐Serrat

Salvadó

Operto

et al. 2019

Human Brain Mapping

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White matter hyperintensities (WMH) have been extensively associated with cognitive impairment and reductions in gray matter volume (GMv) independently. This study explored whether WMH lesion volume mediates the relationship between cerebral patterns of GMv and cognition in 521 (mean age 57.7 years) cognitively unimpaired middle‐aged individuals. Episodic memory (EM) was measured with the Memory Binding Test and executive functions (EF) using five WAIS‐IV subtests. WMH were automatically determined from T2 and FLAIR sequences and characterized using diffusion‐weighted imaging (DWI) parameters. WMH volume was entered as a mediator in a voxel‐wise mediation analysis relating GMv and cognitive performance (with both EM and EF composites and the individual tests independently). The mediation model was corrected by age, sex, education, number of Apolipoprotein E (APOE)‐ε4 alleles and total intracranial volume. We found that even at very low levels of WMH burden in the cohort (median volume of 3.2 mL), higher WMH lesion volume was significantly associated with a widespread pattern of lower GMv in temporal, frontal, and cerebellar areas. WMH mediated the relationship between GMv and EF, mainly driven by processing speed, but not EM. DWI parameters in these lesions were compatible with incipient demyelination and axonal loss. These findings lead to the reflection on the relevance of the control of cardiovascular risk factors in middle‐aged individuals as a valuable preventive strategy to reduce or delay cognitive decline.

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Clinically silent Alzheimer's and vascular pathologies influence brain networks supporting executive function in healthy older adults

Cited by 15 publications

References 68 publications

Attention-Related Brain Activation Is Altered in Older Adults With White Matter Hyperintensities Using Multi-Echo fMRI

Attention-Related Brain Activation Is Altered in Older Adults With White Matter Hyperintensities Using Multi-Echo fMRI

Abnormal Interactions of the Salience Network, Central Executive Network, and Default-Mode Network in Patients With Different Cognitive Impairment Loads Caused by Leukoaraiosis

White matter hyperintensities mediate gray matter volume and processing speed relationship in cognitively unimpaired participants

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