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

TL;DR

This study explores blood-based Alzheimer's disease biomarkers in patients with essential tremor and finds associations with cognitive decline.

Contribution

The study is novel in examining specific blood biomarkers for Alzheimer's disease in essential tremor patients with varying cognitive status.

Findings

Higher concentrations of p-tau217, GFAP, and NfL were linked to greater cognitive difficulty in essential tremor patients.

Lower Aβ42/40 ratios were associated with worse cognitive performance.

Dementia cases showed higher levels of GFAP and NfL compared to cognitively normal cases.

Abstract

Two 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.

Examine blood concentrations of t-tau, p-tau181, p-tau217, Aβ42/40, neurofilament light (NfL) and glial fibrillary acidic protein (GFAP) in ET with a range of cognitive diagnoses.

40 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.

Greater cognitive difficulty was associated with higher blood concentrations of p-tau217, p-tau181, GFAP, and NfL, and a lower Aβ42/40 ratio (p tests for trend < 0.05). Cases with dementia had marginally higher concentrations of p-tau217 (p = 0.06) and higher concentrations of GFAP and NfL (p < 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 (p < 0.05).

Albeit 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.

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