PET of Brain Amyloid and Tau in Mild Cognitive Impairment

Small, Gary W.; Kepe, Vladimir; Ercoli, Linda M.; Siddarth, Prabha; Bookheimer, Susan Y.; Miller, Karen J.; Lavretsky, Helen; Burggren, Alison C.; Cole, Greg M.; Vinters, Harry V.; Thompson, Paul M.; Huang, Sung‐Cheng; Satyamurthy, Nagichettiar; Phelps, Michael E.; Barrio, Jorge R.

doi:10.1056/nejmoa054625

Cited by 646 publications

(567 citation statements)

References 25 publications

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“…One explanation is that a higher degree of white matter microstructural damage, as seen in MCI,24 may be necessary before LV mass index relates to DTI measurements. MCI participants are more likely to have amyloid and tau pathology,25 which have been associated with white matter damage 26. It is possible that in the presence of pathology and more susceptible white matter, as seen in MCI, small changes in LV structure lead to greater changes in white matter microstructure.…”

Section: Discussionmentioning

confidence: 99%

Increased Left Ventricular Mass Index Is Associated With Compromised White Matter Microstructure Among Older Adults

Moore

Liu

Pechman

et al. 2018

JAHA

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BackgroundLeft ventricular (LV) hypertrophy is associated with cerebrovascular disease and cognitive decline. Increased LV mass index is a subclinical imaging marker that precedes overt LV hypertrophy. This study relates LV mass index to white matter microstructure and cognition among older adults with normal cognition and mild cognitive impairment.Methods and ResultsVanderbilt Memory & Aging Project participants free of clinical stroke, dementia, and heart failure (n=318, 73±7 years, 58% male, 39% mild cognitive impairment) underwent brain magnetic resonance imaging, cardiac magnetic resonance, and neuropsychological assessment. Voxelwise analyses related LV mass index (g/m2) to diffusion tensor imaging metrics. Models adjusted for age, sex, education, race/ethnicity, Framingham Stroke Risk Profile, cognitive diagnosis, and apolipoprotein E–ε4 status. Secondary analyses included a LV mass index×diagnosis interaction term with follow‐up models stratified by diagnosis. With identical covariates, linear regression models related LV mass index to neuropsychological performances. Increased LV mass index related to altered white matter microstructure (P<0.05). In models stratified by diagnosis, associations between LV mass index and diffusion tensor imaging were present among mild cognitive impairment participants only (P<0.05). LV mass index was related only to worse visuospatial memory performance (β=−0.003, P=0.036), an observation that would not withstand correction for multiple testing.ConclusionsIn the absence of prevalent heart failure and clinical stroke, increased LV mass index corresponds to altered white matter microstructure, particularly among older adults with clinical symptoms of prodromal dementia. Findings highlight the potential link between subclinical LV remodeling and cerebral white matter microstructure vulnerability.

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Section: Discussionmentioning

confidence: 99%

Increased Left Ventricular Mass Index Is Associated With Compromised White Matter Microstructure Among Older Adults

Moore

Liu

Pechman

et al. 2018

JAHA

View full text Add to dashboard Cite

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“…46 -48 Noninvasive diagnostic methods for tauopathies include positron emission tomography imaging with plaque-binding and especially tangle-binding tracers such as FDDNP, similar to the amyloidbinding radiotracer Pittsburgh compound B. 49,50 …”

Section: Tauopathiesmentioning

confidence: 99%

Tau-Based Treatment Strategies in Neurodegenerative Diseases

2008

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Summary:Neurofibrillary tangles are a characteristic hallmark of Alzheimer's and other neurodegenerative diseases, such as Pick's disease (PiD), progressive supranuclear palsy (PSP), corticobasal degeneration (CBD), and frontotemporal dementia and parkinsonism linked to chromosome 17 (FTDP-17). These diseases are summarized as tauopathies, because neurofibrillary tangles are composed of intracellular aggregates of the microtubule-associated protein tau. The molecular mechanisms of tau-mediated neurotoxicity are not well understood; however, pathologic hyperphosphorylation and aggregation of tau play a central role in neurodegeneration and neuronal dysfunction. The present review, therefore, focuses on therapeutic approaches that aim to inhibit tau phosphorylation and aggregation or to dissolve preexisting tau aggregates. Further experimental therapy strategies include the enhancement of tau clearance by activation of proteolytic, proteasomal, or autophagosomal degradation pathways or anti-tau directed immunotherapy. Hyperphosphorylated tau does not bind microtubules, leading to microtubule instability and transport impairment. Pharmacological stabilization of microtubule networks might counteract this effect. In several tauopathies there is a shift toward four-repeat tau isoforms, and interference with the splicing machinery to decrease four-repeat splicing might be another therapeutic option.

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“…This marker has a unique capability of being able to detect amyloid plaque along with neurofibrillary tangles. It also provides unique detection of AD pathology in the hippocampus [15,16]. However, the ability to bind amyloid plaque, neurofibrillary tangles, Lewy bodies, and prions may hinder the utility of FDNNP for routine imaging to distinguish AD from AD mimics [17][18][19][20].…”

Section: Compounds Of Interestmentioning

confidence: 99%

Amyloid Imaging: Poised for Integration into Medical Practice

Anand

Sabbagh

2017

Neurotherapeutics

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Amyloid imaging represents a significant advance as an adjunct in the diagnosis of Alzheimer's disease (AD) because it is the first imaging modality that identifies in vivo changes known to be associated with the pathogenesis. Initially, 11 C-PIB was developed, which was the prototype for many 18 F compounds, including florbetapir, florbetaben, and flutemetamol, among others. Despite the high sensitivity and specificity of amyloid imaging, it is not commonly used in clinical practice, mainly because it is not reimbursed under current Center for Medicare and Medicaid Services guidelines in the USA. To guide the field in who would be most appropriate for the utility of amyloid positron emission tomography, current studies are underway [Imaging Dementia Evidence for Amyloid Scanning (IDEAS) Study] that will inform the field on the utilization of amyloid positron emission tomography in clinical practice. With the advent of monoclonal antibodies that specifically target amyloid antibody, there is an interest, possibly a mandate, to screen potential treatment recipients to ensure that they are suitable for treatment. In this review, we summarize progress in the field to date.

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PET of Brain Amyloid and Tau in Mild Cognitive Impairment

Cited by 646 publications

References 25 publications

Increased Left Ventricular Mass Index Is Associated With Compromised White Matter Microstructure Among Older Adults

Increased Left Ventricular Mass Index Is Associated With Compromised White Matter Microstructure Among Older Adults

Tau-Based Treatment Strategies in Neurodegenerative Diseases

Amyloid Imaging: Poised for Integration into Medical Practice

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