The use of neuroimaging techniques in the early and differential diagnosis of dementia

Abstract

Dementia is a leading cause of disability and death worldwide. At present there is no disease modifying treatment for any of the most common types of dementia such as Alzheimer's disease (AD), Vascular dementia, Lewy Body Dementia (LBD) and Frontotemporal dementia (FTD). Early and accurate diagnosis of dementia subtype is critical to improving clinical care and developing better treatments. Structural and molecular imaging has contributed to a better understanding of the pathophysiology of neurodegenerative dementias and is increasingly being adopted into clinical practice for early and accurate diagnosis. In this review we summarise the contribution imaging has made with particular focus on multimodal magnetic resonance imaging (MRI) and positron emission tomography imaging (PET). Structural MRI is widely used in clinical practice and can help exclude reversible causes of memory problems but has relatively low sensitivity for the early and differential diagnosis of dementia subtypes. ¹⁸F-fluorodeoxyglucose PET has high sensitivity and specificity for AD and FTD, while PET with ligands for amyloid and tau can improve the differential diagnosis of AD and non-AD dementias, including recognition at prodromal stages. Dopaminergic imaging can assist with the diagnosis of LBD. The lack of a validated tracer for α-synuclein or TAR DNA-binding protein 43 (TDP-43) imaging remain notable gaps, though work is ongoing. Emerging PET tracers such as ¹¹C-UCB-J for synaptic imaging may be sensitive early markers but overall larger longitudinal multi-centre cross diagnostic imaging studies are needed.

Fig. 1. Representative MRI scans in different types of dementia.

The figure shows representative MRI scans from a non-demented control and from patients with Dementia with Lewy Bodies (DLB), Alzheimer’s disease (AD) and frontotemporal lobe degeneration (FTLD). It highlights the characteristic patterns of atrophy with relative preservation of the hippocampus in DLB, severe hippocampal atrophy in AD and temporal pole atrophy in FTLD. These scans are from the Neuroimaging of Inflammation in Memory and Other disorders (NIMROD) study cohort. Images are courtesy of Dr Elijah Mak, University of Cambridge, UK.

Fig. 2. ¹⁸F-Fluorodeoxyglucose (FDG) PET in Alzheimer’s disease (AD) and Dementia with Lewy Bodies (DLB).

FDG PET representative images showing reduced local cerebral metabolic rate of glucose consumption in cases of AD and DLB compared to a non-demented control study participant. The white arrows highlight the relative preservation of the hippocampus and posterior cingulate gyrus in DLB compared to AD and the occipital hypometabolism in DLB. These are FDG PET scans from the Study of the clinical utility, patient preference and cost benefit of SPECT and PET-CT brain imaging in the evaluation and diagnosis of Alzheimer’s Disease (Suspected-AD). Images are courtesy of Dr Michael Firbank, Newcastle University, UK.

Fig. 3. Tau Positron emission tomography in Mild Cognitive Impairment (MCI) and Alzheimer’s Disease (AD).

The figure shows the stereotypical progression of tau binding on 18F-flortaucipir from normal controls (CON) to MCI to AD depicting volume and surface in the left and right panels respectively. These are group-averaged mean maps from the NIMROD study cohort. The top of the coloured bar (red) signifies greater radioligand binding and the bottom of the bar (blue/grey) lower binding. Images are courtesy of Dr Elijah Mak, University of Cambridge, UK.

Fig. 4. Synaptic PET imaging in different types of dementia.

¹¹C-UCBJ PET cases images showing differential loss of synaptic density in cases of people with Alzheimer’s disease (AD), Dementia with Lewy Bodies (DLB), Progressive supranuclear palsy (PSP) and Frontotemporal dementia (FTD) compared to a healthy control. Images are courtesy of Dr Maura Malpetti and Dr Simon Jones, University of Cambridge, UK.