Reconsidering harbingers of dementia: progression of parietal lobe white matter hyperintensities predicts Alzheimer's disease incidence

Brickman, Adam M.; Zahodne, Laura B.; Guzman, Vanessa A.; Narkhede, Atul; Meier, Irene B.; Griffith, Erica Y.; Provenzano, Frank A.; Schupf, Nicole; Manly, Jennifer J.; Stern, Yaakov; Luchsinger, José A.; Mayeux, Richard

doi:10.1016/j.neurobiolaging.2014.07.019

Cited by 202 publications

(198 citation statements)

References 45 publications

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“…The study of Brickman et al [62] showed that the parietal lobe, where early dysfunction was apparent in AD, was strongly interconnected, so the damage to parietal lobes may reflect Wallerian-type degeneration. These studies could illustrate that in the process of progressing to AD, the parietal lobe was really impaired, but unimodal network analysis cannot come to this conclusion.…”

Section: Discussionmentioning

confidence: 99%

Aberrant Connectivity in Mild Cognitive Impairment and Alzheimer Disease Revealed by Multimodal Neuroimaging Data

Li¹,

Wu²,

Xie³

et al. 2018

Neurodegener Dis

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Background: Making use of multimodal data simultaneously to understand the neural mechanism of mild cognitive impairment (MCI) has been in the focus nowadays. The simultaneous use of multimodal data can take advantage of each modality which may only provide the view of one specific aspect of the brain. Objective: To this end, the present study used structural magnetic resonance imaging (sMRI), fluorodeoxyglucose positron emission tomography (FDG-PET) and florbetapir PET to reveal the integrated brain network between MCI and normal controls (NCs). Methods: In this study, 116 MCI, 116 NC and 116 Alzheimer disease (AD) subjects from the Alzheimer's Disease Neuroimaging Initiative were included for the evaluation of the brain covariance graphic model. Sparse inverse covariance estimation was utilized to get the graphic model. Results: The connections among different brain regions were quite different between NC and MCI or between MCI and AD subjects (p < 0.01). The number of connections, which were represented by the covariance among different brain regions in the graphic model, decreased from NC to MCI and then AD, especially in the temporal lobe, occipital-parietal lobe and parietal-temporal lobe. Conclusion: These findings are good evidence to reveal the difference between MCI or AD and NC, and enhance the understanding of MCI.

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Section: Discussionmentioning

confidence: 99%

Aberrant Connectivity in Mild Cognitive Impairment and Alzheimer Disease Revealed by Multimodal Neuroimaging Data

Li¹,

Wu²,

Xie³

et al. 2018

Neurodegener Dis

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“…5,6,98 In the Rotterdam Scan Study, WMHs and brain infarcts at baseline were strongly associated with an increased risk of subsequent development of dementia, including AD. 8,98 This temporality provides strong evidence for a causal relationship between WMHs and cognitive decline and dementia.…”

Section: Wmhs and The Development Of Dementiamentioning

confidence: 99%

“…3,4 Clear evidence exists that WMHs lead to cognitive decline and have a role in the aetiology of dementia. [5][6][7][8] WMHs, together with lacunar infarcts and cerebral microbleeds, are considered to be the primary pathology in subcortical ischaemic vascular dementia (VaD). [9][10][11] Furthermore, vascular factors and cerebrovascular pathologies such as WMHs are increasingly recognized to be involved in the aetiology of Alzheimer disease (AD).…”

Section: Introductionmentioning

confidence: 99%

“…5,8 In dementia research, the focus is largely on the amyloid hypothesis, and the influence of cerebral small vessel disease, including WMHs, is sometimes neglected. However, in order to delay the onset and progression of dementia, vascular factors such as WMHs may be more important than the presence of amyloid, and should, therefore, be acknowledged and addressed.…”

Section: Introductionmentioning

confidence: 99%

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White matter hyperintensities, cognitive impairment and dementia: an update

2015

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White matter hyperintensities (WMHs) in the brain are the consequence of cerebral small vessel disease, and can easily be detected on MRI. Over the past three decades, research has shown that the presence and extent of white matter hyperintense signals on MRI are important for clinical outcome, in terms of cognitive and functional impairment. Large, longitudinal population-based and hospital-based studies have confirmed a dose-dependent relationship between WMHs and clinical outcome, and have demonstrated a causal link between large confluent WMHs and dementia and disability. Adequate differential diagnostic assessment and management is of the utmost importance in any patient, but most notably those with incipient cognitive impairment. Novel imaging techniques such as diffusion tensor imaging might reveal subtle damage before it is visible on standard MRI. Even in Alzheimer disease, which is thought to be primarily caused by amyloid, vascular pathology, such as small vessel disease, may be of greater importance than amyloid itself in terms of influencing the disease course, especially in older individuals. Modification of risk factors for small vessel disease could be an important therapeutic goal, although evidence for effective interventions is still lacking. Here, we provide a timely Review on WMHs, including their relationship with cognitive decline and dementia.

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“…Chronic cerebral hypoxic-ischemic injury, an important factor contributing to many age-related neurodegenerative disorders, 11–13 also appears to involve HIF-1 related pathways. 14 Interestingly, HIF-1 activation is also reduced in aging.…”

Section: Introductionmentioning

confidence: 99%

Deferoxamine, Cerebrovascular Hemodynamics, and Vascular Aging

Sorond

Tan

LaRose

et al. 2015

Stroke

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Background and Purpose Iron chelation therapy is emerging as a novel neuroprotective strategy. The mechanisms of neuroprotection are diverse and include both neuronal and vascular pathways. We sought to examine the effect of iron chelation on cerebrovascular function in healthy aging and to explore whether HIF-1 activation may be temporally correlated with vascular changes Methods We assessed cerebrovascular function (autoregulation, vasoreactivity, neurovascular coupling) and serum concentrations of vascular endothelial growth factor (VEGF) and erythropoietin (EPO), as representative measures of HIF-1 activation, during 6 hours of deferoxamine (DFO) infusion in healthy 24 young and 24 older volunteers in a randomized, blinded, placebo-controlled cross-over study design. Cerebrovascular function was assessed using the transcranial Doppler ultrasound. VEGF and EPO serum protein assays were conducted using the Meso Scale Discovery platform. Results DFO elicited a strong age- and time-dependent increase in the plasma concentrations of EPO and VEGF, which persisted up to 3 hours post infusion (age effect p=0.04, treatment x time p<0.01). DFO infusion also resulted in a significant time- and age-dependent improvement in cerebral vasoreactivity (treatment x time, p<0.01, age p<0.01) and cerebral autoregulation (gain: age x time x treatment p=0.04). Conclusions DFO infusion improved cerebrovascular function, particularly in older individuals. The temporal association between improved cerebrovascular function and increased serum VEGF and EPO concentrations is supportive of shared HIF-1 regulated pathways. Therefore, pharmacological activation of HIF-1 to enhance cerebrovascular function may be a promising neuroprotective strategy in acute and chronic ischemic syndromes, especially in elderly patients. Clinical Trial Registration URL: http://www.clinicaltrials.gov. Unique identifier: NCT013655104.

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Reconsidering harbingers of dementia: progression of parietal lobe white matter hyperintensities predicts Alzheimer's disease incidence

Cited by 202 publications

References 45 publications

Aberrant Connectivity in Mild Cognitive Impairment and Alzheimer Disease Revealed by Multimodal Neuroimaging Data

Aberrant Connectivity in Mild Cognitive Impairment and Alzheimer Disease Revealed by Multimodal Neuroimaging Data

White matter hyperintensities, cognitive impairment and dementia: an update

Deferoxamine, Cerebrovascular Hemodynamics, and Vascular Aging

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