Dementia with Lewy bodies and Parkinson disease dementia – the same or different and is it important?

Biological definitions of neurological diseases are now becoming a reality, although still in the research phase. This development will recategorize neurological diseases, providing objective diagnostics and the promise of therapeutics that target biological mechanisms — similar to the strategy that has proven successful in tumours and other conditions. In this Perspective article, we discuss this development for dementias with dominant Lewy pathology, as the availability of biological assays for this pathology has sparked new interest in a single disease diagnosis for all individuals positive for α-synuclein. On the basis of current evidence, we argue that an α-synuclein assay alone is unlikely to be a specific criterion for a spectrum of clinical syndromes with Lewy pathology or a definitive diagnostic marker for Lewy body dementia. We advocate that one biological assay will not reflect the complex spatiotemporal features of brain pathology. Diverse sequential mechanisms underpin the highly heterogeneous phenotypes and clinicopathological processes of Lewy body dementias. Disease modification, if possible, will be most effective when it targets the early underlying mechanisms, especially those leading to aggressive phenotypes.