High circulating levels of midregional proenkephalin A predict vascular dementia: a population-based prospective study

H Holm,A Fedorowski,E D Nilsson,E Bachus,M Magnusson,O Hansson,O Melander,K Nägga,F Ricci

doi:10.1038/s41598-020-64998-y

H Holm, A Fedorowski + Show 7 more

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https://doi.org/10.1038/s41598-020-64998-y

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Abstract

Midregional Pro-enkephalin A (MR-PENK A) and N-terminal Protachykinin A (NT-PTA) have been associated with vascular dementia. However, the longitudinal relationship between these biomarkers and incident dementia has not been fully investigated. In the population-based Malmö Preventive Project, circulating levels of MR-PENK A and NT-PTA were determined in a random sample of 5,323 study participants (mean age: 69 ± 6 years) who were followed-up over a period of 4.6 ± 1.6 years. The study sample included 369 patients (7%) who were diagnosed in the same period with dementia. We analyzed relationship of MR-PENK A and NT-PTA with the risk of developing dementia by using multivariable-adjusted Cox regression models adjusted for traditional risk factors. Increased plasma levels of MR-PENK A were associated with higher risk of incident vascular dementia whereas no associations were found with all-cause or Alzheimer dementia. The risk of vascular dementia was mainly conferred by the highest quartile of MR-PENK as compared with lower quartiles. Elevated levels of NT-PTA yielded significant association with all-cause dementia or dementia subtypes. Elevated plasma concentration of MR-PENK A independently predicts vascular dementia in the general population. MR-PENK A may be used as an additional tool for identifying vascular subtype in ambiguous dementia cases.

Highlights

Dementia is a collective term for neurodegenerative diseases associated with impairment of cognitive functions including memory, speech, executive functions, and mental speed[1]
We aimed to investigate whether elevated plasma levels of MR-PENK A and N-terminal Protachykinin A (NT-PTA) could be used for prediction of dementia subtypes in a community-dwelling older population
Plasma concentration of MR-PENK A and NT-PTA was increased for individuals with vascular dementia compared with other dementia subtypes (Supplementary Table 1)

Summary

Introduction

Dementia is a collective term for neurodegenerative diseases associated with impairment of cognitive functions including memory, speech, executive functions, and mental speed[1]. Since cardiovascular comorbidities are frequently found in individuals with Alzheimer, the coexistence with vascular dementia is substantial[4]. Overlapping features of both Alzheimer and vascular dementia define mixed dementia. Cerebrospinal fluid biomarkers signaling neurodegenerative disease offers the opportunity to distinguish pure dementia cases from those with mixed dementia. The stable precursor fragments of the neuropeptides enkephalin (proenkephalin A [MR-PENK A]) and substance P (protachykinin A [NT-PTA]) have been found in blood and cerebrospinal fluid (CSF)[7,8] and have recently been used for the assessment of vascular dementia, Alzheimer’s disease and neuroinflammatory disorders[9]. We aimed to investigate whether elevated plasma levels of MR-PENK A and NT-PTA could be used for prediction of dementia subtypes in a community-dwelling older population

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