Neuroimaging biomarkers in prodromal Dementia with Lewy Bodies: a systematic literature review

Aims: We systematically reviewed the neuroimaging studies published so far that employed MRI, PET (FDG, FP-CIT), and SPECT to study the recently defined prodromal stage of dementia with Lewy Bodies (pro-DLB). We aimed to provide an updated and more precise depiction of the structural and functional brain alterations that are specific to pro-DLB and that differentiate it from physiological ageing and the predementia stage of other diseases, especially MCI due to AD. Materials: We performed a literature search using PubMed and Scopus and retrieved 8956 unique records employing MRI, PET and SPECT to examine pro-DLB patients. Method: After applying inclusion and exclusion criteria, 40 records were included in the systematic review: 15 studies assessed structural gray matter (GM) and white matter (WM) integrity and 31 investigated functional metabolism, perfusion, and resting-state connectivity alterations. Results: In pro-DLB, frontal lobe areas (including the prefrontal cortex) were characterized by significantly lower metabolism and perfusion, consistent cortical atrophy, and WM damage. Volumetric reductions were found in the insular cortex, which also showed heightened metabolism. A pattern of increased metabolism and perfusion and of structural GM and WM damage characterized the lateral and ventral temporal lobe, comprising the fusiform and lingual gyri; notably, greater functionality was also found in the parahippocampal cortex and hippocampi in the medial temporal lobe. Hypometabolism and hypoperfusion marked the parietal and occipital lobes, with localized atrophy in the medial occipital lobe (i.e., the visual system) and posterior parietal cortex (encompassing the precuneus and supramarginal/angular gyrus), with less consistent results regarding the cingulate island sign. Subcortically, we reported atrophy and microstructural damage in the nucleus basalis of Meynert, and hypometabolism and cortical thinning in the thalamus together with WM changes in the tract connecting the thalamus to the pedunculopontine nucleus. Lastly, dopamine transporter uptake was reduced in the basal ganglia. Discussion: Structural and functional damage was already present at the prodromal stage of DLB. Frontal and parieto-occipital alterations in structure and function may be associated with deficits in attention and executive functions and in visuo-perceptual and visuo-spatial abilities, respectively, which are commonly observed in DLB patients. Degeneration of cholinergic and dopaminergic transmission appeared substantial at this disease stage. Conclusions: We confirmed that some of the neuroimaging biomarkers proposed for pro-DLB were actually useful for the identification of these patients; additionally, we highlighted that other biomarkers might be used to support the recognition of pro-DLB patients in the clinical context.