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Review
. 2023 Feb 7;24(4):3325.
doi: 10.3390/ijms24043325.

Imaging Methods Applicable in the Diagnostics of Alzheimer's Disease, Considering the Involvement of Insulin Resistance

Petra Hnilicova  1 , Ema Kantorova  2 , Stanislav Sutovsky  3 , Milan Grofik  2 , Kamil Zelenak  4 , Egon Kurca  2 , Norbert Zilka  5 , Petra Parvanovova  6 , Martin Kolisek  1
Affiliations
Review

Imaging Methods Applicable in the Diagnostics of Alzheimer's Disease, Considering the Involvement of Insulin Resistance

Petra Hnilicova et al. Int J Mol Sci. .

Abstract

Alzheimer's disease (AD) is an incurable neurodegenerative disease and the most frequently diagnosed type of dementia, characterized by (1) perturbed cerebral perfusion, vasculature, and cortical metabolism; (2) induced proinflammatory processes; and (3) the aggregation of amyloid beta and hyperphosphorylated Tau proteins. Subclinical AD changes are commonly detectable by using radiological and nuclear neuroimaging methods such as magnetic resonance imaging (MRI), computed tomography (CT), positron emission tomography (PET), and single-photon emission computed tomography (SPECT). Furthermore, other valuable modalities exist (in particular, structural volumetric, diffusion, perfusion, functional, and metabolic magnetic resonance methods) that can advance the diagnostic algorithm of AD and our understanding of its pathogenesis. Recently, new insights into AD pathoetiology revealed that deranged insulin homeostasis in the brain may play a role in the onset and progression of the disease. AD-related brain insulin resistance is closely linked to systemic insulin homeostasis disorders caused by pancreas and/or liver dysfunction. Indeed, in recent studies, linkages between the development and onset of AD and the liver and/or pancreas have been established. Aside from standard radiological and nuclear neuroimaging methods and clinically fewer common methods of magnetic resonance, this article also discusses the use of new suggestive non-neuronal imaging modalities to assess AD-associated structural changes in the liver and pancreas. Studying these changes might be of great clinical importance because of their possible involvement in AD pathogenesis during the prodromal phase of the disease.

Keywords: Alzheimer’s disease; diffusion magnetic resonance; functional magnetic resonance; insulin resistance; liver; magnetic resonance spectroscopy; magnetic resonance volumetry; neuroimaging; pancreas; perfusion magnetic resonance; positron emission tomography.

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Conflict of interest statement

The funders had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript; or in the decision to publish the results.

Figures

Figure 1
Figure 1
Example of MR neuroimaging (T1-weighted MRI at 3 Tesla MR-scanner) of a control subject (70-year-old female), of an MCI patient proceeding to AD in two years (72-year-old male), and of an AD patient (75-year-old female) in axial, sagittal, and coronal sections. The differences are visually subtle, but the increased atrophy in the medial temporal lobe and the enlarged ventricles are apparent in MRI.
Figure 2
Figure 2
Example of MRI (I.; T1-weighted MRI at 3 Tesla MR-scanner) and MR-volumetric (II.; MR-volumetry performed on Freesurfer software) neuroimaging of a control subject (40-year-old female) and AD patient (42-year-old female) in axial, coronal, and sagittal sections. In AD, the apparent atrophy is shown across the white matter (III. 3D model of the whole brain) as well as in several brain structures (IV. 3D model of selected brain areas; atrophy of the hippocampus/yellow, atrophy of the thalamus/green, enlarged lateral ventricles/purple).
Figure 3
Figure 3
Example of MRI (T1-weighted MRI at 3 Tesla MR-scanner), DWI, and DTI (performed on DSI studio software incorporating MATLAB postscripts) neuroimaging of a control subject (50-year-old male) and AD patient (56-year-old female). AD exhibits more restricted diffusion in the tissue, a worse global network density, and lost white matter fiber tracts. Abbreviations: ADC, apparent diffusion coefficient; DTI, diffusion tensor imaging; DWI, diffusion weighted imaging; FA, fractional anisotropy.
Figure 4
Figure 4
Example of 1H MRS neuroimaging (T1-weighted MRI at 3 Tesla MR-scanner) obtained by the multivoxel spectroscopy approach with the presented spectra (one selected voxel indicated with the red square and arrow) showing the main metabolite peaks: total creatine (tCr), total choline (tCho), total N-acetyl-aspartate (tNAA), and myo-Inositol (mIns). The 1H MRS spectra for a control subject (50-year-old female) and AD patient (55-year-old female) are depicted with the typical metabolic peak changes being indicated by black arrows (↓: decreased, ↑: increased). Metabolic maps of the brain tissue are also shown (tNAA, mIns, and tCho maps).
Figure 5
Figure 5
Example of 1H MRS neuroimaging (T1-weighted MRI at 3 Tesla MR-scanner) measured by the multivoxel Mescher–Garwood-editing MRS approach with the represented spectra (one selected voxel indicated with the red square and arrow) showing the main metabolite peaks: glutamate with glutamine (Glx) and γ-aminobutyric acid (GABA). The 1H MRS spectra for a control subject (35-year-old female) and AD patient (42-year-old female) are depicted with the typical metabolic peak changes being indicated by black arrows (↓: decreased, ↑: increased). Metabolic maps of the brain tissue are also shown (GABA and Glx maps).
Figure 6
Figure 6
Example of 18F-flutemetamol (Vizamyl) PET neuroimaging of a control subject (73-year-old male) and AD patient (72-year-old male). Note the visualization of subtle cortical atrophy with enlarged ventricles (T1-weighted MRI at 3 Tesla MR-scanner) and increased retention of the Vizamyl radiotracer demonstrating the presence of Aβ deposition in the AD brain tissue, compared with that of the control subject.
Figure 7
Figure 7
Insulin signaling pathway. Transmembrane structure depicts insulin receptor complex sensing insulin (INS) and neuritin (N; a member of the neurotrophic factor family, promotes neuritogenesis, neuronal survival, and synaptic maturation). Abbreviations: Akt/PKB, Akt protein kinase B; AMP, adenosine monophosphate; cAMP, cyclic adenosine monophosphate; GSK3, glycogen synthase kinase-3 β; IRS-1/2, insulin receptor substrate 1 and 2; mTOR, mammalian target of rapamycin; PDE3b, phosphodiesterase 3B; PDK1, phosphoinositide-dependent protein kinase 1; PI3K, phosphoinositide 3-kinase; PIP2, phosphatidylinositol 4,5-bisphosphate; PIP3, phosphatidylinositol (3,4,5)-trisphosphate; PKA, protein kinase A; PKC λ/ζ, protein kinase C λ/ζ.
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