Neuroanatomical and clinical correlates of prodromal dementia with Lewy bodies: a systematic literature review of neuroimaging findings

Prodromal Dementia with Lewy bodies (pro-DLB) has been recently defined; however, the neuroanatomical and functional correlates of this stage have not yet been univocally established. This study aimed to systematically review neuroimaging findings focused on pro-DLB. A literature search of works employing MRI, PET, and SPECT was performed. Forty records were included: 15 studies assessed gray matter (GM) and white matter (WM) integrity, and 31 investigated metabolism, perfusion, and resting-state connectivity. Results showed that, in pro-DLB, frontal lobe areas were characterized by decreased function, cortical atrophy, and WM damage. Volumetric reductions were found in the insula, which also showed heightened metabolism. A pattern of hypofunction and structural damage was observed in the lateral and ventral temporal lobe; instead, the parahippocampal cortex and hippocampus exhibited greater function. Hypofunction marked parietal and occipital regions, with additional atrophy in the medial occipital lobe and posterior parietal cortex. Subcortically, atrophy and microstructural damage in the nucleus basalis of Meynert were reported, and dopamine transporter uptake was reduced in the basal ganglia. Overall, structural and functional damage was already present in pro-DLB and was coherent with the possible clinical onset. Frontal and parieto-occipital alterations may be associated with deficits in attention and executive functions and in visuo-perceptual/visuo-spatial abilities, respectively. Degeneration of cholinergic and dopaminergic transmission appeared substantial at this disease stage. This review provided an updated and more precise depiction of the brain alterations that are specific to pro-DLB and valuable to its differentiation from physiological aging and other dementias.