Imaging Techniques in Alzheimer’s Disease: A Review of Applications in Early Diagnosis and Longitudinal Monitoring

Abstract

Background. Alzheimer’s disease (AD) is a progressive neurodegenerative disorder affecting many individuals worldwide with no effective treatment to date. AD is characterized by the formation of senile plaques and neurofibrillary tangles, followed by neurodegeneration, which leads to cognitive decline and eventually death. Introduction. In AD, pathological changes occur many years before disease onset. Since disease-modifying therapies may be the most beneficial in the early stages of AD, biomarkers for the early diagnosis and longitudinal monitoring of disease progression are essential. Multiple imaging techniques with associated biomarkers are used to identify and monitor AD. Aim. In this review, we discuss the contemporary early diagnosis and longitudinal monitoring of AD with imaging techniques regarding their diagnostic utility, benefits and limitations. Additionally, novel techniques, applications and biomarkers for AD research are assessed. Findings. Reduced hippocampal volume is a biomarker for neurodegeneration, but atrophy is not an AD-specific measure. Hypometabolism in temporoparietal regions is seen as a biomarker for AD. However, glucose uptake reflects astrocyte function rather than neuronal function. Amyloid-β (Aβ) is the earliest hallmark of AD and can be measured with positron emission tomography (PET), but Aβ accumulation stagnates as disease progresses. Therefore, Aβ may not be a suitable biomarker for monitoring disease progression. The measurement of tau accumulation with PET radiotracers exhibited promising results in both early diagnosis and longitudinal monitoring, but large-scale validation of these radiotracers is required. The implementation of new processing techniques, applications of other imaging techniques and novel biomarkers can contribute to understanding AD and finding a cure. Conclusions. Several biomarkers are proposed for the early diagnosis and longitudinal monitoring of AD with imaging techniques, but all these biomarkers have their limitations regarding specificity, reliability and sensitivity. Future perspectives. Future research should focus on expanding the employment of imaging techniques and identifying novel biomarkers that reflect AD pathology in the earliest stages.

Diagnostic Fluid Biomarkers in Alzheimer’s Disease: Blood and Cerebrospinal Fluid

“…The pathological processes underpinning AD involve the accumulation of Aβ1-42 in the brain decades prior to the onset of clinical symptoms, followed by a decrease in cortical metabolism [32][33][34]. Diagnosis and prognosis of AD are currently dependent on costly imaging approaches and neurophysiological tests [6,35]. CSF biomarkers directly reflect the brain environment and have been investigated for use in disease diagnosis and prognosis [7,36].…”

“…The limitations of currently available MR imaging-based approaches are evident [6]. As such, the development of plasma-based biomarkers for early diagnosis and disease-monitoring provides a key solution for treatment and prevention of AD.…”

“…Therefore, early diagnosis and prevention of AD are crucial in order to reduce disease severity and improve prognosis [5]. Current methods for monitoring AD pathology include neuroimaging biomarkers using magnetic resonance imaging (MRI) and positron emission tomography (PET) [6], and cerebrospinal fluid (CSF) biomarkers [6,7]. However, neuroimaging biomarkers are expensive and availability of these is limited [6].…”

“…Current methods for monitoring AD pathology include neuroimaging biomarkers using magnetic resonance imaging (MRI) and positron emission tomography (PET) [6], and cerebrospinal fluid (CSF) biomarkers [6,7]. However, neuroimaging biomarkers are expensive and availability of these is limited [6]. Further, the measurement of CSF biomarkers requires lumbar puncture and is invasive, with numerous challenges associated with monitoring disease progression and developing disease-modifying treatments [7].…”

Editorial for “Individualized Prediction of Early Alzheimer's Disease Based on MRI Radiomics, Clinical and Laboratory Examinations: A 60‐Month Follow‐up Study”

“…6 However, these findings are not specific to AD and the change might be very subtle during the MCI stage. Several novel imaging techniques have emerged, 7 and the radiomics approach, which extracts a large number of imaging features and mines invisible but meaningful data, has been under vigorous investigation in numerous fields such as the diagnosis of tumors, psychiatric disorders, and neurodegenerative diseases. 8 Tang et al applied this radiomics approach to the diagnosis of AD, and found that their method of extracting the requisite features from the whole cerebral cortex (using FreeSurfer), subcortical nucleus (using SPM12), and white matter lesions successfully predicted the time to progression (TTP) from MCI to AD, based on a 5-year follow-up and validation study.…”