Aβ-related hyperactivation in frontoparietal control regions in cognitively normal elderly

Oh, Hwamee; Steffener, Jason; Razlighi, Qolamreza R.; Habeck, Christian; Liú, Dan; Gazes, Yunglin; Janicki, Sarah; Stern, Yaakov

doi:10.1016/j.neurobiolaging.2015.08.016

Cited by 36 publications

(26 citation statements)

References 72 publications

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“…Several previous studies have also observed positive relationships between AD pathology and BOLD response during episodic memory tasks (Sperling et al, 2009; Mormino et al, 2012; Elman et al, 2014) and executive tasks (Gordon et al, 2015; Oh et al, 2015). Considering WMH-BOLD relationships in CN older adults, there have been reports of both positive (Lockhart et al, 2015) and negative correlations (Nordahl et al, 2006; Venkatraman et al, 2010).…”

Section: Discussionmentioning

confidence: 66%

“…Separate studies conducted with CN older adults have reported functional brain alterations during the performance of executive tasks associated with WMHs (Nordahl et al, 2006; Venkatraman et al, 2010) and more recently with AD pathology (Gordon et al, 2015; Oh et al, 2015). However, few if any studies have explored the impact of both WMH and AD pathology on functional brain activations using a common task paradigm and participant group.…”

Section: Introductionmentioning

confidence: 99%

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

Gold

Brown

Hakun

et al. 2017

Neurobiology of Aging

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Aging is associated with declines in executive function. We examined how executive functional brain systems are influenced by clinically silent Alzheimer’s disease (AD) pathology and cerebral white matter hyperintensities (WMHs). Twenty-nine younger adults and thirty-four cognitively normal older adults completed a working memory paradigm while functional magnetic resonance imaging (fMRI) was performed. Older adults further underwent lumbar cerebrospinal fluid (CSF) draw for assessment of AD pathology and FLAIR imaging for assessment of WMHs. Accurate working memory performance in both age groups was associated with high fronto-visual functional connectivity (fC). However, in older adults, higher expression of fronto-visual fC was linked with lower levels of clinically silent AD pathology. In addition, AD pathology and WMHs were each independently related to increased fMRI response in the left dorsolateral prefrontal cortex, a pattern associated with slower task performance. Our results suggest that clinically silent AD pathology is related to lower expression of a fronto-visual fC pattern supporting executive task performance. Further, our findings suggest that AD pathology and WMHs appear to be linked with ineffective increases in frontal response in CN older adults.

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Section: Discussionmentioning

confidence: 66%

Section: Introductionmentioning

confidence: 99%

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

Gold

Brown

Hakun

et al. 2017

Neurobiology of Aging

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“…SUVrs are obtained by comparing tracer uptake in target regions to a reference area devoid of specific uptake. By comparing SUVrs in AD patients with SUVrs obtained in healthy volunteers, previous studies derived cut-off thresholds that could discriminate between amyloid positive and amyloid negative individuals ( Barthel et al, 2011 ; Chiotis et al, 2015 ; Fleisher, 2011 ; Nordberg et al, 2013 ; Oh et al, 2015 ; Ong et al, 2015 ; Vandenberghe et al, 2010 ). Semi-quantitative amyloid burden is generally estimated on average (composite) SUVr based on neocortical regions, usually including frontal, parietal, temporal and cingulate regions ( Clark et al, 2012 ; Fleisher, 2011 ).…”

Section: Introductionmentioning

confidence: 99%

Low-dose CT for the spatial normalization of PET images: A validation procedure for amyloid-PET semi-quantification

Presotto

Iaccarino

Sala

et al. 2018

NeuroImage: Clinical

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The reference standard for spatial normalization of brain positron emission tomography (PET) images involves structural Magnetic Resonance Imaging (MRI) data. However, the lack of such structural information is fairly common in clinical settings. This might lead to lack of proper image quantification and to evaluation based only on visual ratings, which does not allow research studies or clinical trials based on quantification.PET/CT systems are widely available and CT normalization procedures need to be explored. Here we describe and validate a procedure for the spatial normalization of PET images based on the low-dose Computed Tomography (CT) images contextually acquired for attenuation correction in PET/CT systems. We included N = 34 subjects, spanning from cognitively normal to mild cognitive impairment and dementia, who underwent amyloid-PET/CT (18F-Florbetaben) and structural MRI scans. The proposed pipeline is based on the SPM12 unified segmentation algorithm applied to low-dose CT images. The validation of the normalization pipeline focused on 1) statistical comparisons between regional and global 18F-Florbetaben-PET/CT standardized uptake value ratios (SUVrs) estimated from both CT-based and MRI-based normalized PET images (SUVrCT, SUVrMRI) and 2) estimation of the degrees of overlap between warped gray matter (GM) segmented maps derived from CT- and MRI-based spatial transformations.We found negligible deviations between regional and global SUVrs in the two CT and MRI-based methods. SUVrCT and SUVrMRI global uptake scores showed negligible differences (mean ± sd 0.01 ± 0.03). Notably, the CT- and MRI-based warped GM maps showed excellent overlap (90% within 1 mm).The proposed analysis pipeline, based on low-dose CT images, allows accurate spatial normalization and subsequent PET image quantification. A CT-based analytical pipeline could benefit both research and clinical practice, allowing the recruitment of larger samples and favoring clinical routine analysis.

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“…First, there was no age-matched prevalence of FBB positivity in the normal subjects in this study. Only few studies on FBB have reported evidence that a proportion of cognitively normal older subjects reveal Aβ deposits in the brain [37]. Most studies have determined Aβ positivity in persons without dementia using PIB PET [28].…”

Section: Discussionmentioning

confidence: 99%

Extremely Low Prevalence of Amyloid Positron Emission Tomography Positivity in Parkinson's Disease without Dementia

Mashima¹,

Ito²,

Kameyama

et al. 2017

Eur Neurol

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Background: Most cases of dementia with Lewy bodies (DLB) show Alzheimer's disease pathology-like senile plaques and neurofibrillary tangles. Several studies have also revealed a high prevalence of positive amyloid imaging with positron emission tomography (PET) in DLB and moderate prevalence in Parkinson's disease (PD) with dementia. However, it remains unclear in PD without dementia as to when the brain β amyloid (Aβ) burden begins and progresses. Our study aimed to determine the prevalence of Aβ deposition in PD without dementia using amyloid PET. Methods: This was a cross-sectional study on 33 patients with PD without dementia, of whom 21 had normal cognition and 12 met the criteria for PD-mild cognitive impairment. All subjects underwent neuropsychological assessment and [¹⁸F] florbetaben (FBB) PET. Results: All subjects had Lewy body-related disorders, displaying a significantly reduced myocardial [¹²³I] metaiodobenzylguanidine uptake. The cortical FBB-binding pattern in all subjects, including APOE e4 carriers, suggested negative Aβ deposition. Conclusion: Patients with PD without dementia exhibit an extremely low prevalence of Aβ positivity compared with those reported in cognitively normal elderly controls. Further longitudinal imaging studies and long-term follow-up are needed; however, our findings provide novel insights for understanding Aβ metabolism in PD.

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Aβ-related hyperactivation in frontoparietal control regions in cognitively normal elderly

Cited by 36 publications

References 72 publications

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

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

Low-dose CT for the spatial normalization of PET images: A validation procedure for amyloid-PET semi-quantification

Extremely Low Prevalence of Amyloid Positron Emission Tomography Positivity in Parkinson's Disease without Dementia

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