Proton Magnetic Resonance Spectroscopy in Common Dementias—Current Status and Perspectives

Abstract

Dementia occurs mainly in the elderly and is associated with cognitive decline and impairment of activities of daily living. The most common forms of dementia are Alzheimer's disease (AD), vascular dementia (VD), dementia with Lewy bodies (DLB), and frontotemporal dementia (FTD). To date, there are no causal options for therapy, but drug and non-drug treatments can positively modulate the course of the disease. Valid biomarkers are needed for the earliest possible and reliable diagnosis, but so far, such biomarkers have only been established for AD and require invasive and expensive procedures. In this context, proton magnetic resonance spectroscopy (1 H-MRS) provides a non-invasive and widely available technique for investigating the biochemical milieu of brain tissue in vivo. Numerous studies have been conducted for AD, but for VD, DLB, and FTD the number of studies is limited. Nevertheless, MRS can detect measurable metabolic alterations in common dementias. However, most of the studies conducted are too heterogeneous to assess the potential use of MRS technology in clinical applications. In the future, technological advances may increase the value of MRS in dementia diagnosis and treatment. This review summarizes the results of MRS studies conducted in common dementias and discusses the reasons for the lack of transfer into clinical routine.

Ex vivo MRI and histopathology detect novel iron-rich cortical inflammation in frontotemporal lobar degeneration with tau versus TDP-43 pathology

“…( Irwin et al, 2015 ) Indeed, while some frontotemporal dementia (FTD) clinical syndromes have group-level statistical associations with one of these proteinopathies, the majority of FTD syndromes do not reliably predict pathology. ( Irwin et al, 2015 , Gorno-Tempini et al, 2011 , Höglinger et al, 2017 , Giannini et al, 2019 , Irwin et al, 2018 , Perry et al, 2017 , Spinelli et al, 2017 ) Moreover, while various degenerative processes can be detected using structural, ( McKiernan and O’Brien, 2017 , McMillan et al, 2014 , Rohrer et al, 2009 , Whitwell et al, 2005 , Whitwell et al, 2015 , Perry et al, 2017 ), diffusion, ( McMillan et al, 2014 , Whitwell et al, 2010 , Illán-Gala et al, 2019 ), and spectroscopic MRI, ( Maul et al, 2020 , Murley et al, 20202020 ), as well as PET, ( Kim et al, 2019 , Whitwell et al, 2020 ); there is currently no method to directly sensitize traditional MRI, or any other in vivo imaging technology, including molecular imaging, to the specific protein inclusions or pathological features that would allow in vivo discrimination of patients with tau and/or TDP-43 inclusions in FTLD. In this report, we explore the novel combination of histopathology and T 2 *-weighted (T2*w) ex vivo 7 T MRI for the purpose of developing a more reliable, data-driven approach to diagnosis of pathology in FTLD spectrum disorders.…”

Diagnóstico da doença de Alzheimer: recomendações do Departamento Científico de Neurologia Cognitiva e do Envelhecimento da Academia Brasileira de Neurologia

“…As an example, although the MRI proton magnetic resonance spectroscopy technique - which assesses brain metabolites such as N-acetylaspartate (Naa), creatine (Cr), and myo-inositol (mI) - shows differences between groups of patients with and without AD, it still has many limitations and technique heterogeneity as to be applied in clinical practice as a marker of the disease. The main findings of the technique are a decrease in NAA and NAA/Cr ratio and an increase in mI and mI/Cr ratio 100 .…”

Saturation Transfer MRI for Detection of Metabolic and Microstructural Impairments Underlying Neurodegeneration in Alzheimer’s Disease

“…Since changes in metabolism precede any structural changes in AD, MRS may appear to be an ideal technique for AD diagnosis. A recent review of MRS in common dementias has found decreased N-acetylaspartate (NAA) in posterior cingulate cortex, hippocampus, temporal, and parietal lobes in patients with AD [ 42 ]. Increased myo-inositol (mIns) and total choline levels, relative to total creatine (tCr), are also observed in the posterior cingulate cortex [ 42 ].…”

“…A recent review of MRS in common dementias has found decreased N-acetylaspartate (NAA) in posterior cingulate cortex, hippocampus, temporal, and parietal lobes in patients with AD [ 42 ]. Increased myo-inositol (mIns) and total choline levels, relative to total creatine (tCr), are also observed in the posterior cingulate cortex [ 42 ]. However, the utility of MRS in prediction or differential diagnosis of AD has been hampered by a number of technical issues.…”

“…The signal measured by MRS is low compared to that measured with MRI, meaning that it takes considerably longer to acquire, and only some metabolites are present in large enough quantities to be measured [ 43 ]. MRS typically measures only one voxel at a time, so most research has focused only on a few select brain regions, making meta-analyses difficult [ 42 ]. Magnetic resonance spectroscopic imaging (MRSI) can solve this problem, but at the cost of reduced data quality compared with MRS [ 44 ].…”