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. 2020 May 15;10(1):8027.
doi: 10.1038/s41598-020-64998-y.

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

H Holm  1   2 , K Nägga  3 , E D Nilsson  3 , F Ricci  4   5 , O Melander  4   6 , O Hansson  3 , E Bachus  4   7 , A Fedorowski  4   6 , M Magnusson  4   6   8
Affiliations

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

H Holm et al. Sci Rep. .

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.

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Conflict of interest statement

The authors declare no competing interests.

Figures

Figure 1
Figure 1
Malmö Preventive Project and re-screening program.
Figure 2
Figure 2
(A,B) Kaplan-Meier curves for cumulative incidence of (A) all-cause dementia and (B) Alzheimer disease incidence stratified according to quartiles of MR-PENK A; Q1 < 49.9 pmol/l; Q2 49.9–60.6 pmol/l; Q3 60.7–73.2 pmol/l; Q4 > 73.2 pmol/l.
Figure 3
Figure 3
(A,B) Kaplan-Meier curves for cumulative incidence of (A) all-cause dementia and (B) Alzheimer disease incidence stratified according to quartiles of NT-PTA; Q1 < 66 pmol/l; Q2 66–79.2 pmol/l; Q3 79.2–94.8 pmol/l; Q4 > 94.8 pmol/l.
Figure 4
Figure 4
Kaplan-Meier curves for cumulative vascular dementia incidence from rescreening (2002–2006) to the end of follow-up (December 31, 2009) among 5,292 participants of Malmö Preventive Project stratified according to quartiles of MR-PENK; Q1 < 49.9 pmol/l; Q2 49.9–60.6 pmol/l; Q3 60.7–73.2 pmol/l; Q4 > 73.2 pmol/l.
Figure 5
Figure 5
Diagnostic yield of MR-PENK A in relation to dementia subtypes by receiver operating characteristic curve analysis.
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