There are a number of potential mechanisms for this, including initiating or accelerating the accumulation of tau, amyloid, synuclein and TDP-43 pathologies.7,68 Neurodegenerative diseases, such as Alzheimer's disease, frontotemporal lobar degeneration and CTE have long prodromal phases, where progressive pathology is present without clinical symptoms of dementia.69-71 If RHI accelerates neurodegenerative processes this might increase the dementia risk or bring forward the age at which it manifests.56 The gene discussed is TARDBP; the disease is early-onset autosomal dominant Alzheimer disease.