Autonomic and neurosensory disorders in dementia with lewy bodies: prevalence and neural basis in the AlphaLewyMA cohort

In dementia with Lewy bodies (DLB), autonomic and neurosensory disorders can precede neurocognitive symptoms by several years. Improving knowledge of these symptoms is essential to avoid associated complications and could reveal potential diagnostic biomarkers and shed light on the pathophysiological mechanisms involved in the early stages of the disease. Within the AlphaLewyMA cohort, 142 probable DLB patients at the mild cognitive impairment or dementia stages were screened for 10 autonomic and three neurosensory disorders, at 0, 6, 12, 18, 24, 36, 48, 60, 72, 84 and 96 months of follow-up, using a standardized questionnaire and a test for neurogenic orthostatic hypotension. We described the prevalence and evolution over time of these disorders. To explore their neuroanatomical correlates, we performed whole-brain voxel-based morphometry (VBM) analyses on grey matter volumes in a subsample of 116 patients with MRI data. The mean age was 71, and 51% were men. Reports of autonomic and neurosensory disorders were very common in our main sample. As some fluctuated during follow-up, repeated screening had a major impact on their prevalence, with 95.7% of the patients declaring an autonomic disorder at least once during the follow-up and 76.8% a neurosensory disorder. The six most frequent symptoms over the follow-up were rhinorrhoea (79.3%), dry mouth (73.3%), sexual dysfunction (70.6%), neurogenic orthostatic hypotension (68.9%), urinary dysfunction (68.0%) and constipation (67.2%). In VBM analysis, dryness (whether ocular, nasal or oral) and severe taste disorders were associated with lower grey matter volumes in the left insula and in the left putamen and caudate nucleus, respectively. Reports of autonomic and neurosensory disorders were very common and some seemed to fluctuate, highlighting the need for regular, systematic screening. Among these disorders, several symptoms little studied so far in DLB turned out to be the most frequently reported by our patients (rhinorrhoea, dry mouth and sexual dysfunction) and could provide interesting clues for diagnosis. VBM analysis may support an involvement of the insula and certain basal ganglia in dryness-type symptoms and taste disorders. Further prospective studies combining self-reporting and objective measures are needed to refine our results.