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EAN 2026 | Clinical markers of progression in prodromal alpha-synucleinopathies

Dario Arnaldi, MD, PhD, University of Genoa, Genoa, Italy, discusses clinical markers of disease progression across the prodromal to overt alpha-synucleinopathy continuum. He highlights REM sleep behavior disorder as a key early indicator of Parkinson’s disease and dementia with Lewy bodies, alongside subtle motor, cognitive, autonomic, and olfactory changes that may help identify individuals at high risk. This interview took place at the 12th Congress of the European Academy of Neurology (EAN) in Geneva, Switzerland.

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Transcript

Yeah, we know very well that alpha-synucleinopathies, such as Parkinson’s disease and dementia with Lewy bodies, start decades before the emergence of overt clinical syndromes, such as overt parkinsonism or full-blown dementia. The strongest risk factors and the strongest prodromal sign for alpha-synucleinopathies is the presence of REM sleep behavior disorder, in which patients act out their dreams, often during episodes in which they can harm themselves or their bed partner...

Yeah, we know very well that alpha-synucleinopathies, such as Parkinson’s disease and dementia with Lewy bodies, start decades before the emergence of overt clinical syndromes, such as overt parkinsonism or full-blown dementia. The strongest risk factors and the strongest prodromal sign for alpha-synucleinopathies is the presence of REM sleep behavior disorder, in which patients act out their dreams, often during episodes in which they can harm themselves or their bed partner. So this is the first tip. You need to use this presence of behaviors as red flags. Then, if a patient has REM sleep behavior disorder, you might then want to check for subtle motor signs or cognitive signs that may not be enough yet for the full diagnosis of Parkinson’s disease and dementia with Lewy bodies, but then they can be in a prodromal stage. There are other markers that can also be useful. For example, the presence of hyposmia or orthostatic hypotension, that often patients with REM sleep behavior disorder have, and this increases the risk of developing the full-blown syndrome over time.

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