Blood-based Alzheimer's disease biomarkers and cognitive decline in essential tremor

BackgroundTwo epidemiological studies demonstrated an association between essential tremor (ET) and prevalent dementia as well as substantially elevated risks of incident dementia among ET cases. At this early point, the underlying pathophysiology of ET-dementia is not known. In vivo biomarkers of Alzheimer's disease (AD) and neurodegeneration could help bridge the gap between the pathophysiological processes that present in the context of ET-dementia.ObjectiveExamine blood concentrations of t-tau, p-tau181, p-tau217, Aβ_42/40, neurofilament light (NfL) and glial fibrillary acidic protein (GFAP) in ET with a range of cognitive diagnoses.Methods40 ET cases (mean age = 81.5 ± 7.3; including 20 normal cognition (NC), 12 cognitively normal with some weaknesses, 4 mild cognitive impairment, and 4 dementia) were enrolled in a study of cognitive performance in ET, during which phlebotomy was performed.ResultsGreater cognitive difficulty was associated with higher blood concentrations of p-tau217, p-tau181, GFAP, and NfL, and a lower Aβ_42/40 ratio (<i>p</i> tests for trend < 0.05). Cases with dementia had marginally higher concentrations of p-tau217 (<i>p</i> = 0.06) and higher concentrations of GFAP and NfL (<i>p</i> < 0.05) than cases with NC. Furthermore, higher concentrations of p-tau217, GFAP, and NfL were associated with lower cognitive test scores across multiple cognitive domains (<i>p</i> < 0.05).ConclusionsAlbeit based on a small sample of cases, our findings suggest a potential role of blood-based biomarkers as markers for cognitive function in ET patients. Cognitive decline in ET may be due to underlying neurodegenerative processes involving tau and perhaps Aβ pathology.