MRS in neurodegenerative dementias, prodromal syndromes and at‐risk states: A systematic review of the literature

McKiernan, Elizabeth; Su, Li; O’Brien, John

doi:10.1002/nbm.4896

Cited by 7 publications

(13 citation statements)

References 118 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…This enables us to study metabolic alterations associated with AD progression. 14 One of the most valuable MRI modalities in AD is resting-state functional MRI, which has been used to show how AD impairs multiple functional networks across the brain, including the default mode network, the salience network, or the dorsal attention network. 11 Nuclear imaging techniques such as PET and single photon emission computerized tomography are methods of choice to study important hallmarks of AD by using radioactive tracers that specifically bind to brain metabolites, protein aggregates, or neurotransmitters, or can visualize glucose metabolism, inflammatory events, and other processes involved in the AD pathophysiology.…”

Section: Neuroimaging From Cellular To Full System Level In Admentioning

confidence: 99%

Preserving cognitive function in patients with Alzheimer's disease: The Alzheimer's disease neuroprotection research initiative (ADNRI)

Liu,

van Beusekom,

et al. 2023

Neuroprotection

View full text Add to dashboard Cite

The global trend toward aging populations has resulted in an increase in the occurrence of Alzheimer's disease (AD) and associated socioeconomic burdens. Abnormal metabolism of amyloid‐β (Aβ) has been proposed as a significant pathomechanism in AD, supported by results of recent clinical trials using anti‐Aβ antibodies. Nonetheless, the cognitive benefits of the current treatments are limited. The etiology of AD is multifactorial, encompassing Aβ and tau accumulation, neuroinflammation, demyelination, vascular dysfunction, and comorbidities, which collectively lead to widespread neurodegeneration in the brain and cognitive impairment. Hence, solely removing Aβ from the brain may be insufficient to combat neurodegeneration and preserve cognition. To attain effective treatment for AD, it is necessary to (1) conduct extensive research on various mechanisms that cause neurodegeneration, including advances in neuroimaging techniques for earlier detection and a more precise characterization of molecular events at scales ranging from cellular to the full system level; (2) identify neuroprotective intervention targets against different neurodegeneration mechanisms; and (3) discover novel and optimal combinations of neuroprotective intervention strategies to maintain cognitive function in AD patients. The Alzheimer's Disease Neuroprotection Research Initiative's objective is to facilitate coordinated, multidisciplinary efforts to develop systemic neuroprotective strategies to combat AD. The aim is to achieve mitigation of the full spectrum of pathological processes underlying AD, with the goal of halting or even reversing cognitive decline.

show abstract

Section: Neuroimaging From Cellular To Full System Level In Admentioning

confidence: 99%

Preserving cognitive function in patients with Alzheimer's disease: The Alzheimer's disease neuroprotection research initiative (ADNRI)

Liu,

van Beusekom,

et al. 2023

Neuroprotection

View full text Add to dashboard Cite

show abstract

“…Alterations have also been reported in the concentration of other metabolites, though less consistently. Creatine may be lower in MCI and AD 7 but has been found to increase with age. 11 Both increases and decreases in Cho in AD have been reported, with the lack of consistency potentially attributable to the routine usage of acetylcholinesterase inhibitors.…”

Section: Introductionmentioning

confidence: 96%

“… 4-6 Alterations have also been found in other dementias including dementia with Lewy bodies (DLB), Parkinson’s disease dementia (PDD) and frontotemporal dementia (FTD) compared to normal ageing. Spatial patterns of metabolite changes are different between different dementia types, for example, changes in AD are reported largely in the posterior cingulate cortex (PCC) and hippocampus while in FTD frontal changes predominate 7 . A summary of metabolites detectable at 3T and relevant to studies of AD can be found in Table 1 .…”

Section: Introductionmentioning

confidence: 99%

Investigating the brain’s neurochemical profile at midlife in relation to dementia risk factors

Dounavi,

McKiernan,

Langsen

et al. 2024

Brain Communications

Self Cite

View full text Add to dashboard Cite

Changes in the brain’s physiology in Alzheimer’s disease (AD) are thought to occur early in the disease’s trajectory. In this study our aim was to investigate the brain’s neurochemical profile in a midlife cohort in relation to risk factors for future dementia using single voxel proton magnetic resonance spectroscopy (MRS). Participants in the multi-site PREVENT-Dementia study (age range 40-59 year old) underwent 3T MRS with the spectroscopy voxel placed in the posterior cingulate/precuneus region. Using LCModel, we quantified the absolute concentrations of myo-inositol (mI), total N-acetylaspartate (tNAA), total creatine (tCr), choline (Cho), glutathione (GSH) and glutamate-glutamine (Glx) for 406 participants (mean age 51.1; 65.3% female). Underlying partial volume effects were accounted for by applying a correction for the presence of cerebrospinal fluid in the MRS voxel. We investigated how metabolite concentrations related to apolipoprotein ε4 (APOE4) genotype, dementia family history (FHD), a risk score (Cardiovascular Risk Factors, Aging and Incidence of Dementia -CAIDE) for future dementia including non-modifiable and potentially-modifiable factors and dietary patterns (adherence to Mediterranean diet). FHD was associated with decreased tNAA and no differences were found between APOE4 carriers and non-carriers. A higher CAIDE score related to higher mI, Cho, tCr and Glx, an effect which was mainly driven by older age and a higher body mass index. Greater adherence to the Mediterranean diet was associated with lower Cho, mI and tCr; these effects did not survive correction for multiple comparisons. The observed associations suggest that at midlife the brain demonstrates subtle neurochemical changes in relation to both inherited and potentially-modifiable risk factors for future dementia.

show abstract

“…MRS is the only non-invasive technique for in-vivo detection and quantification of metabolite concentrations in the human brain. It can provide insight into the neurochemistry of various brain diseases 1 , potentially leading to the discovery of clinically relevant biomarkers 2–6 and enabling a better understanding of the underlying biochemical processes.…”

Section: Introductionmentioning

confidence: 99%

“…• MM: Macromolecule 1 , potentially leading to the discovery of clinically relevant biomarkers [2][3][4][5][6] and enabling a better understanding of the underlying biochemical processes.…”

mentioning

confidence: 99%

Macromolecule modelling for improved metabolite quantification using short echo time brain¹H MRS at 3 T and 7 T: The PRaMM Model

Dell’Orco,

Riemann,

Ellison

et al. 2023

Preprint

View full text Add to dashboard Cite

PurposeTo improve reliability of metabolite quantification at both, 3 T and 7 T, we propose a novel parametrized macromolecules quantification model (PRaMM) for brain1H MRS, in which the ratios of macromolecule peak intensities are used as soft constraints.MethodsFull- and metabolite-nulled spectra were acquired in three different brain regions with different ratios of grey and white matter from six healthy volunteers, at both 3 T and 7 T. Metabolite-nulled spectra were used to identify highly correlated macromolecular signal contributions and estimate the ratios of their intensities. These ratios were then used as soft constraints in the proposed PRaMM model for quantification of full spectra. The PRaMM model was validated by comparison with a single component macromolecule model and a macromolecule subtraction technique. Moreover, the influence of the PRaMM model on the repeatability and reproducibility compared to those other methods was investigated.ResultsThe developed PRaMM model performed better than the two other approaches in all three investigated brain regions. Several estimates of metabolite concentration and their Cramér-Rao lower bounds were affected by the PRaMM model reproducibility, and repeatability of the achieved concentrations were tested by evaluating the method on a second repeated acquisitions dataset. While the observed effects on both metrics were not significant, the fit quality metrics were improved for the PRaMM method (p≤0.0001). Minimally detectable changes are in the range 0.5 – 1.9 mM and percent coefficients of variations are lower than 10% for almost all the clinically relevant metabolites. Furthermore, potential overparameterization was ruled out.ConclusionHere, the PRaMM model, a method for an improved quantification of metabolites was developed, and a method to investigate the role of the MM background and its individual components from a clinical perspective is proposed.

show abstract

MRS in neurodegenerative dementias, prodromal syndromes and at‐risk states: A systematic review of the literature

Abstract: Background: In recent years, MRS has benefited from increased MRI field strengths, new acquisition protocols and new processing techniques. This review aims to determine how this has altered our understanding of MRS neurometabolic markers in neurodegenerative dementias.

Cited by 7 publications

References 118 publications

Preserving cognitive function in patients with Alzheimer's disease: The Alzheimer's disease neuroprotection research initiative (ADNRI)

Preserving cognitive function in patients with Alzheimer's disease: The Alzheimer's disease neuroprotection research initiative (ADNRI)

Investigating the brain’s neurochemical profile at midlife in relation to dementia risk factors

Macromolecule modelling for improved metabolite quantification using short echo time brain¹H MRS at 3 T and 7 T: The PRaMM Model

Contact Info

Product

Resources

About

MRS in neurodegenerative dementias, prodromal syndromes and at‐risk states: A systematic review of the literature

Abstract: Background: In recent years, MRS has benefited from increased MRI field strengths, new acquisition protocols and new processing techniques. This review aims to determine how this has altered our understanding of MRS neurometabolic markers in neurodegenerative dementias.

Cited by 7 publications

References 118 publications

Preserving cognitive function in patients with Alzheimer's disease: The Alzheimer's disease neuroprotection research initiative (ADNRI)

Preserving cognitive function in patients with Alzheimer's disease: The Alzheimer's disease neuroprotection research initiative (ADNRI)

Investigating the brain’s neurochemical profile at midlife in relation to dementia risk factors

Macromolecule modelling for improved metabolite quantification using short echo time brain1H MRS at 3 T and 7 T: The PRaMM Model

Contact Info

Product

Resources

About

Macromolecule modelling for improved metabolite quantification using short echo time brain¹H MRS at 3 T and 7 T: The PRaMM Model