Imaging Biomarkers in Alzheimer's Disease: A Practical Guide for Clinicians

Abstract

Although recent developments in imaging biomarkers have revolutionized the diagnosis of Alzheimer's disease at early stages, the utility of most of these techniques in clinical setting remains unclear. The aim of this review is to provide a clear stepwise algorithm on using multitier imaging biomarkers for the diagnosis of Alzheimer's disease to be used by clinicians and radiologists for day-to-day practice. We summarized the role of most common imaging techniques and their appropriate clinical use based on current consensus guidelines and recommendations with brief sections on acquisition and analysis techniques for each imaging modality. Structural imaging, preferably MRI or alternatively high resolution CT, is the essential first tier of imaging. It improves the accuracy of clinical diagnosis and excludes other potential pathologies. When the results of clinical examination and structural imaging, assessed by dementia expert, are still inconclusive, functional imaging can be used as a more advanced option. PET with ligands such as amyloid tracers and ¹⁸F-fluorodeoxyglucose can improve the sensitivity and specificity of diagnosis particularly at the early stages of the disease. There are, however, limitations in using these techniques in wider community due to a combination of lack of facilities and expertise to interpret the findings. The role of some of the more recent imaging techniques including tau imaging, functional MRI, or diffusion tensor imaging in clinical practice, remains to be established in the ongoing and future studies.

Keywords: Alzheimer’s disease; biomarkers; guidelines; imaging; magnetic resonance imaging; positron emission tomography.

Fig.1

Visual assessment of MTL and hippocampal atrophy. a) largest vertical width of choroid fissure; b) width of temporal horn; c) maximum vertical height of hippocampal formation. ↑, increase; ↓, decrease; N, normal.

Fig.2

Summary of structural MRI applications in assessment of AD based on current guidelines and literature review.

Fig.3

MRI images of common types of dementia in axial, coronal, and sagittal planes, a) early AD with hippocampal and MTL atrophy; b) PCA with superior posterior parietal lobes atrophy; c) logopenic variant of PPA with atrophy in left temporoparietal junction; note more prominent left sided atrophy of posterior and lateral temporal lobes; d) semantic variant of PPA with atrophy in anterior and lateral temporal lobes; e) non-fluent variant of PPA with left frontal operculum and insular atrophy.

Fig.4

MRI (top), FDG-PET (middle), and PiB-PET (bottom) images of a typical AD case in axial (a), coronal (b) and sagittal (c) planes showing hypometabolism in parietal and temporal lobes in FDG-PET and extensive cortical amyloid deposition in PiB-PET.

Fig.5

Stepwise algorithm of PET imaging in the evaluation of AD. Patients who fulfill the criteria for PET imaging, can be imaged by FDG-PET or SPECT. If FDG-PET is inconclusive, amyloid imaging will be the next step. The dashed lines are demonstrating the role of tau PET when it becomes clinically available.