Evidence for cortical “disconnection” as a mechanism of age-related cognitive decline

O’Sullivan, Michael; Jones, Derek K.; Summers, Paul; Morris, Robin G.; Williams, Steven; Markus, Hugh S.

doi:10.1212/wnl.57.4.632

Cited by 730 publications

(577 citation statements)

References 28 publications

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“…Note: To render FA-SES regression plots more interpretable, participants' SES values on the ISP were converted such that higher scores now reflected higher levels of SES (by subtracting each participant's score from 100) (2013) 35:2045-20562004; O'Sullivan et al 2001;Pfefferbaum et al 2000).…”

Section: Discussionmentioning

confidence: 99%

“…The unique correlations in the senior group raise the possibility that high SES may neuroprotect some agerelated frontal WM integrity declines. The anatomical specificity of the observed SES-frontal relationship may in part reflect that frontal WM tracts, because they are especially vulnerable to age-related declines (Head et al 2004;O'Sullivan et al 2001;Salat et al 2005a, b), also carry greater chance of incurring protective benefits from high SES than other regions.…”

Section: Discussionmentioning

confidence: 99%

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Socioeconomic status is positively correlated with frontal white matter integrity in aging

Johnson

Kim

Gold

2012

AGE

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Socioeconomic status (SES) is an important reserve variable which has been shown to benefit the aging brain's macrostructure. However, it remains unknown whether SES affects age-related changes in the brain's white matter (WM) microstructure. Here, we used diffusion tensor imaging to explore the relationship between SES and three components of the diffusion tensor [fractional anisotropy (FA), axial diffusivity, and radial diffusivity (DR)]. Participants were 40 (16 male) cognitively normal young adults (mean age=33.3 years, SD=4.27) and 44 (19 male) cognitively normal community dwelling seniors (mean age=66.2 years, SD= 7.5). Age-related FA declines were observed across a large portion of the WM skeleton. However, seniors with high SES showed lower age-related WM integrity declines in three frontal tracts: the right anterior corona radiata and bilateral portions of WM underlying the superior frontal gyri (SFG-WM). Positive SES-FA correlations were primarily driven by negative DR-SES correlations, suggesting that SES may buffer age-related declines in myelin. The functional significance of high SES in these frontal tracts was demonstrated through positive correlations with working memory performance. Possible mechanisms through which SES may attenuate the effects of age on frontal WM integrity are discussed.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Socioeconomic status is positively correlated with frontal white matter integrity in aging

Johnson

Kim

Gold

2012

AGE

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“…Executive function has been shown to correlate with age-related declines in diffusion anisotropy and increases in mean diffusivity (O'Sullivan, et al 2001a), and reading ability was correlated with a measure of fiber tract organization in a group of healthy and reading-impaired adults (Klingberg, et al 2000). Reduced integrity of the association white matter fiber tracts was seen in patients with Alzheimer's Disease (Rose, et al 2000) relative to normal controls.…”

Section: Introductionmentioning

confidence: 99%

“…Various studies investigating effects of aging (O'Sullivan, et al 2001a;Rose, et al 2000), depression (Steffens, et al 2002), multiple sclerosis (Edwards, et al 2001;Rovaris, et al 2002), or neurological abnormalities (Mulhern, et al 2001;O'Sullivan, et al 2001b) have demonstrated a connection between white matter properties and cognition. Executive function has been shown to correlate with age-related declines in diffusion anisotropy and increases in mean diffusivity (O'Sullivan, et al 2001a), and reading ability was correlated with a measure of fiber tract organization in a group of healthy and reading-impaired adults (Klingberg, et al 2000).…”

Section: Introductionmentioning

confidence: 99%

Cognitive functions correlate with white matter architecture in a normal pediatric population: A diffusion tensor MRI study

Schmithorst¹,

Wilke²,

Dardzinski³

et al. 2005

Human Brain Mapping

368

233

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A possible relationship between cognitive abilities and white matter structure as assessed by magnetic resonance diffusion tensor imaging (DTI) was investigated in the pediatric population. DTI was performed on 47 normal children ages 5–18. Using a voxelwise analysis technique, the fractional anisotropy (FA) and mean diffusivity (MD) were tested for significant correlations with Wechsler full‐scale IQ scores, with subject age and gender used as covariates. Regions displaying significant positive correlations of IQ scores with FA were found bilaterally in white matter association areas, including frontal and occipito‐parietal areas. No regions were found exhibiting correlations of IQ with MD except for one frontal area significantly overlapping a region containing a significant correlation with FA. The positive direction of the correlation with FA is the same as that found previously with age, and indicates a positive relationship between fiber organization and/or density with cognitive function. The results are consistent with the hypothesis that regionally specific increased fiber organization is a mechanism responsible for the normal development of white matter tracts. Hum Brain Mapp, 2005. © 2005 Wiley‐Liss, Inc.

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“…A related possibility is that the diffuse bilateral frontal patterns of activation we observed in older subjects across tasks may reflect a nonspecific recruitment that results from failure of inhibitory processes (Logan et al 2002). Recent studies examining white matter diffusion show age-related decreases in white matter integrity that may be related to reduced functional connectivity (O'Sullivan et al 2001;Pfefferbaum et al 2005). Degradation of white matter is particularly prominent in frontal regions.…”

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confidence: 99%

Changing channels: An fMRI study of aging and cross-modal attention shifts

2006

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Age-related deficits in visual selective attention suggest that the efficiency of inhibitory processes is particularly affected by aging. To investigate whether processing inefficiencies observed in visual attention are similar in auditory attention and when shifting attention across modalities, we conducted an FMRI study with healthy young and older adults using a task that required sustained auditory and visual selective attention and cross-modal attention shifts. Older adults in this study performed as well as the younger adults, but showed age-related differences in BOLD responses. The most striking of these differences were bilateral frontal and parietal regions of significantly increased activation in older adults during both focused and shifting attention. Our data suggest that this increased activation did not reflect new recruitment, but reliance on brain regions typically used by younger adults when task demands are greater. Older adults' activation patterns suggested that even during focused attention conditions they were "shifting" attention to stimuli in the unattended modality. Increased activation during processing of both task-relevant and task-irrelevant information implies age-related loss of processing selectivity. These patterns may reflect both task-specific compensatory neural recruitment and degradation of sensory inhibition. 2Selective attention modulates sensory response to enhance selected relative to non-selected information. Electrophysiological studies have shown that the neural response in visual cortex is increased when visual information is attended (Heinze et al. 1994;Hillyard et al. 1998;Mangun et al. 1998). However, attention driven modulation of sensory cortex is not simple signal enhancement (gain), but also reflects neural specificity for the attended information that results from some combination of augmentation of selected and inhibition of non-selected or less relevant stimulation (Murray and Wojciulik 2004).While selective attention may remain grossly intact with normal aging, some components of attentional processing are affected. Hasher and Zacks (Hasher and Zacks 1988) proposed a model in which age-related deficits in attentional selectivity underlie changes in memory function. They suggested that an ineffective inhibitory system would allow irrelevant information into working memory buffers resulting in the association of large numbers of less specific memory traces. Additionally, an inefficient inhibitory system would affect the ability to suppress irrelevant pathways during memory retrieval and may reflect a central mechanism underlying both distractibility and memory deficits in older adults. A number of studies have suggested that there are age-related decreases in attention modulated neural specificity -most commonly observed as a decreased efficiency in the inhibition of unattended or less relevant information. Single cell recordings in senescent monkeys have shown significant reduction in selectivity of neurons in primary visual cortex that may reflect...

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Evidence for cortical “disconnection” as a mechanism of age-related cognitive decline

Cited by 730 publications

References 28 publications

Socioeconomic status is positively correlated with frontal white matter integrity in aging

Socioeconomic status is positively correlated with frontal white matter integrity in aging

Cognitive functions correlate with white matter architecture in a normal pediatric population: A diffusion tensor MRI study

Changing channels: An fMRI study of aging and cross-modal attention shifts

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