High field 1H MRS of the hippocampus after donepezil treatment in Alzheimer disease

Bartha, Robert; Smith, Morgan; Rupsingh, Raul; Rylett, R. Jane; Wells, Jennie; Borrie, Michael

doi:10.1016/j.pnpbp.2007.12.011

Cited by 46 publications

(47 citation statements)

References 65 publications

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“…The fact that the increase of Cho/Cr levels in striatum of A␤PP/PS1 mice is partially mitigated by treatment with the acetylcholine-esterase inhibitor donepezil [70] raises the possibility that Cho/Cr levels could be used as a biomarker of therapeutic efficacy in AD trials. This result is also in line with a study made in AD patients, showing decreased levels of Cho/Cr after four months of donepezil treatment [71].…”

Section: Discussionsupporting

confidence: 92%

Systematic Evaluation of Magnetic Resonance Imaging and Spectroscopy Techniques for Imaging a Transgenic Model of Alzheimer's Disease (AβPP/PS1)

Esteras

Alquézar

Antequera

et al. 2012

JAD

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Abstract. Murine models of Alzheimer's disease (AD) provide means to detect and follow biomarker changes similar to those observed in humans. Non-invasive biomarkers, such as those provided by magnetic resonance imaging (MRI) and spectroscopy (MRS) methods are highly desirable, however, systematic studies of in vivo MRI/MRS methods to characterize the cerebral morphology and metabolic pattern of these mice remain scarce. We investigated sixteen consecutive slices from the brain of wild-type and A␤PP/PS1 mice, obtaining a collection of T 2 -weighted, diffusion weighted and magnetization transfer weighted images as well as 1 H PRESS spectra from the cortical and subcortical areas. Compared to controls, A␤PP/PS1 mice show significant regional hyperintensities in T 2 -weighted images of the cerebral cortex, significant ventricular enlargement, and decreased hippocampal area and fractional magnetization transfer. MRS demonstrated an increase in the ratio of choline (Cho) to creatine (Cr) in the cortical and subcortical areas of the transgenic animals. A logistic regression classifier was implemented considering all parameters investigated, and revealed the most characteristic changes and allowed for the correct classification of control and A␤PP/PS1 mice. In summary, the present results provide a useful frame to evaluate optimal MRI/MRS biomarkers for the characterization of AD models, potentially applicable in drug discovery processes, because of their non-invasive and repeatable nature in longitudinal studies.

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Section: Discussionsupporting

confidence: 92%

Systematic Evaluation of Magnetic Resonance Imaging and Spectroscopy Techniques for Imaging a Transgenic Model of Alzheimer's Disease (AβPP/PS1)

Esteras

Alquézar

Antequera

et al. 2012

JAD

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“…For example, a transient increase in tNAA concentration was associated with short-term functional response during donepezil treatment in Alzheimer disease, suggesting that tNAA also reflects functional integrity and recovery (137). Other studies have shown a decreased mIns/tCr ratio following donepezil treatment (138) and an increased Glu level after galantamine treatment for Alzheimer disease (139).…”

Section: Special Review: Clinical Proton Mr Spectroscopy In Central Nmentioning

confidence: 99%

Clinical Proton MR Spectroscopy in Central Nervous System Disorders

Öz¹,

Alger²,

Barker³

et al. 2014

Radiology

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356

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A large body of published work shows that proton (hydrogen 1 [ 1 H]) magnetic resonance (MR) spectroscopy has evolved from a research tool into a clinical neuroimaging modality. Herein, the authors present a summary of brain disorders in which MR spectroscopy has an impact on patient management, together with a critical consideration of common data acquisition and processing procedures. The article documents the impact of 1 H MR spectroscopy in the clinical evaluation of disorders of the central nervous system. The clinical usefulness of 1 H MR spectroscopy has been established for brain neoplasms, neonatal and pediatric disorders (hypoxia-ischemia, inherited metabolic diseases, and traumatic brain injury), demyelinating disorders, and infectious brain lesions. The growing list of disorders for which 1 H MR spectroscopy may contribute to patient management extends to neurodegenerative diseases, epilepsy, and stroke. To facilitate expanded clinical acceptance and standardization of MR spectroscopy methodology, guidelines are provided for data acquisition and analysis, quality assessment, and interpretation. Finally, the authors offer recommendations to expedite the use of robust MR spectroscopy methodology in the clinical setting, including incorporation of technical advances on clinical units.q RSNA, 2014 Online supplemental material is available for this article. G.O. (e-mail: gulin@cmrr.umn.edu). 2 The complete list of authors and affiliations is at the end of this article.q RSNA, 2014 Note: This copy is for your personal non-commercial use only. To order presentation-ready copies for distribution to your colleagues or clients, contact us at www.rsna.org/rsnarights. Radiology H MR Spectrum of the Brain: Metabolites and Their Biomarker PotentialMR spectroscopy provides a very different basic "readout" than MR imaging, namely a spectrum rather than an techniques were developed. These early localization techniques included pointresolved spectroscopy (PRESS) (1,2) and stimulated echo acquisition mode (STEAM) (3), methods that are now widely used in clinical MR spectroscopy applications.Preliminary studies revealed large differences in metabolite levels in acute stroke (4), chronic multiple sclerosis (5), and brain tumors compared with healthy brain (6). Although this work stimulated a surge of interest in 1 H MR spectroscopy for diagnosing and assessing CNS disorders during the early days of the "Decade of the Brain" (1990)(1991)(1992)(1993)(1994)(1995)(1996)(1997)(1998)(1999), many suboptimal patient studies (7) and the lack of consistent guidelines have led to a situation where, 20 years later, MR spectroscopy is still considered an "investigational technique" by some medical professionals and health care organizations. However, the ability to make an early, noninvasive diagnosis or to increase confidence in a suspected diagnosis is highly valued by patients and clinicians alike. As a result, an increasing number of imaging centers are incorporating MR spectroscopy into their clinical protocols for brain...

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“…A small and uncontrolled trial with 17 patients treated with donepezil for 4 months showed a correlation between cognitive function and NAA level changes in the parietal lobe. 44 In another study with 15 AD patients treated with donepezil the NAA levels in the right hippocampus decreased after 4 months with no changes in cognitive function [45] . A randomized trial comparing donepezil with Memantine for 6 months showed no significant differences in clinical scales and metabolite levels.…”

Section: Mrs To Track Progression Of Admentioning

confidence: 95%

The contribution of magnetic resonance spectroscopy as biomarker in Alzheimer’s disease

Modrego

2012

JBGC

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The use of biomarkers is growing in the early detection of Alzheimer's disease (AD). Although some biomarkers such as medial temporal lobe volumetry, amyloid Positron Emision Tomography (PET), and Aβ42 in CSF are being widely used, there is no clear consensus about the best biomarker to be used in each phase of the disease. Magnetic Resonance Spectroscopy (MRS) of the brain is less known as biomarker but has proven useful according to cross-sectional and longitudinal studies. This technique measures metabolite levels that reflect the degree of pathology in the brain. N-acetyl aspartate (NAA), a marker of neuronal density, decreases and Myo-inositol, a marker of glial proliferation, increases as the disease progresses. Decreased NAA levels have been detected in the prodromal phases of AD and even in presymptomatic stages in carriers of tau and amyloid protein mutations. Longitudinal studies have demonstrated good correlation between NAA levels and progression of AD, even in spite of treatment with cholinesterase inhibitors. From clinical trials we have learned that the current therapies have a modest effect on AD progression and that they do not have neuroprotective effects. This modest effect is reflected in the modest or null changes in metabolite levels in clinical trials using MRS as biomarker.

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High field 1H MRS of the hippocampus after donepezil treatment in Alzheimer disease

Cited by 46 publications

References 65 publications

Systematic Evaluation of Magnetic Resonance Imaging and Spectroscopy Techniques for Imaging a Transgenic Model of Alzheimer's Disease (AβPP/PS1)

Systematic Evaluation of Magnetic Resonance Imaging and Spectroscopy Techniques for Imaging a Transgenic Model of Alzheimer's Disease (AβPP/PS1)

Clinical Proton MR Spectroscopy in Central Nervous System Disorders

The contribution of magnetic resonance spectroscopy as biomarker in Alzheimer’s disease

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