Brain-first vs. body-first in Lewy body disease.

Brain-first vs. body-first in Lewy body disease. 

Friday Jan. 31st 08.30-09.00 AM
Per Borghammer, Professor, MD, PhD, DMSc 

     Lewy body diseases (LBDs) are heterogeneous disorders characterized by motor symptoms and a multitude of non-motor symptoms including autonomic, sleep, psychiatric symptoms, and dementia. LBDs are special among the neurodegenerative diseases, since the defining pathology (Lewy pathology) involves not only the CNS but also the peripheral autonomic nervous system. Mounting evidence support that the first Lewy pathology arises outside the brain, in either the enteric nervous system of the gut or in the olfactory epithelium – perhaps induced by external triggers such as toxins or infections.

     This lecture covers recent evidence supporting that Lewy pathology commonly originates in the gut (body-first) or the olfactory bulb/amygdala (brain-first). The pathology then spreads through the neural connectome and leads to different clinical subtypes of the disease. Body-first PD shows early, marked involvement of the autonomic nervous system before diagnosis, whereas brain-first patients typically do not develop autonomic dysfunction until after diagnosis. Other factors, such as genetic risks and the presence of co-pathologies (especially Alzheimer-type pathology) also influence the clinical phenotype and progression rates. It is argued that that clinical DLB phenotype often arises as a consequence of body-first Lewy body disease with concomitant Alzheimer’s co-pathology.

   The implications of this novel understanding for future research will be discussed.