Background: Increased somatostatin plasma concentration has been found in patients with vascular dementia. However, it is unknown whether or not somatostatin levels may predict dementia development in the general population. To this end, we sought to assess the association of circulating N-terminal prosomatostatin (NT-proSST) with incident dementia among community-dwelling older adults. Methods: In the prospective population-based Malmö Preventive Project, 5,347 study participants (mean age: 69 ± 6years; 70% men) provided plasma for the determination of NT-proSST concentration. Of these, 373 participants (7%) were diagnosed with dementia (120 Alzheimer's disease, 83 vascular, 102 mixed, and 68 other aetiology) during a follow-up period of 4.6 ± 1.3 years. The association of NT-proSST with the risk of dementia and its subtypes was studied using multivariable-adjusted Cox regression models controlling for age, gender, body mass index, systolic blood pressure, antihypertensive treatment, smoking, diabetes, lipid levels and prevalent stroke. Results: Higher levels of NT-proSST were significantly associated with an increased risk of vascular dementia (hazard ratio [HR] per 1 SD: 1.29; 95% CI 1.05-1.59; p = 0.016), whereas no association was observed with Alzheimer's disease (HR per 1 SD: 0.99; 95% CI 0.81-1.20; p = 0.91), all-cause dementia (HR per 1 SD: 1.04; 95% CI 0.94-1.16; p = 0.44), and mixed dementia (HR per 1 SD: 0.98; 95% CI 0.79-1.21; p = 0.84). Levels of NT-proSST above 563 pmol/L (highest quartile) conferred distinctly increased risk of vascular dementia (HR 1.66; 95% CI 1.05-2.63; p = 0.029) compared with lower values. Conclusions: Higher levels of circulating N-terminal-prosomatostatin are associated with increased incidence of vascular dementia. Our findings might be of importance for the understanding of dementia development in older adults.

Waldemar G, Dubois B, Emre M, Georges J, McKeith IG, Rossor M, et al: Recommendations for the diagnosis and management of Alzheimer's disease and other disorders associated with dementia: EFNS guideline. Eur J Neurol 2007;14:e1-e26.
Jorm AF, Jolley D: The incidence of dementia: a meta-analysis. Neurology 1998;51:728-733.
Robinson L, Tang E, Taylor JP: Dementia: timely diagnosis and early intervention. BMJ 2015;350:h3029.
Rizzi L, Rosset I, Roriz-Cruz M: Global epidemiology of dementia: Alzheimer's and vascular types. Biomed Res Int 2014;2014:908915.
Formichi P, Parnetti L, Radi E, Cevenini G, Dotti MT, Federico A: CSF biomarkers profile in CADASIL-A model of pure vascular dementia: usefulness in differential diagnosis in the dementia disorder. Int J Alzheimers Dis 2010;2010:pii:959257.
Jagtap A, Gawande S, Sharma S: Biomarkers in vascular dementia: a recent update. Bio Genomic Med 2015;7:43-56.
Justin BN, Turek M, Hakim AM: Heart disease as a risk factor for dementia. Clin Epidemiol 2013;5:135-145.
Fillit H, Nash DT, Rundek T, Zuckerman A: Cardiovascular risk factors and dementia. Am J Geriatr Pharmacother 2008;6:100-118.
Pantoni L, Poggesi A, Inzitari D: Cognitive decline and dementia related to cerebrovascular diseases: some evidence and concepts. Cerebrovasc Dis 2009;27(suppl 1):191-196.
Miralbell J, Lopez-Cancio E, Lopez-Oloriz J, Arenillas JF, Barrios M, Soriano-Raya JJ, et al: Cognitive patterns in relation to biomarkers of cerebrovascular disease and vascular risk factors. Cerebrovasc Dis 2013;36:98-105.
Shen Y, Gao HM: Serum somatostatin and neuron-specific enolase might be biochemical markers of vascular dementia in the early stage. Int J Clin Exp Med 2015;8:19471-19475.
Hedback T, Almgren P, Nilsson PM, Melander O: N-terminal prosomatostatin as a risk marker for cardiovascular disease and diabetes in a general population. J Clin Endocrinol Metab 2016;101:3437-3444.
Fedorowski A, Stavenow L, Hedblad B, Berglund G, Nilsson PM, Melander O: Orthostatic hypotension predicts all-cause mortality and coronary events in middle-aged individuals (The Malmo Preventive Project). Eur Heart J 2010;31:85-91.
Fava C, Sjogren M, Montagnana M, Danese E, Almgren P, Engstrom G, et al: Prediction of blood pressure changes over time and incidence of hypertension by a genetic risk score in Swedes. Hypertension 2013;61:319-326.
Nilsson ED, Melander O, Elmstahl S, Lethagen E, Minthon L, Pihlsgard M, et al: Copeptin, a marker of vasopressin, predicts vascular dementia but not Alzheimer's disease. J Alzheimers Dis 2016;52:1047-1053.
Jaffe M: Ueber den Niederschlag, welchen Pikrinsäure in normalen Harn erzeugt und über eine neue reaction des Kreatinins. Z Physiol Chem 1986;10:391-400.
Struck J: Google Patents, Assignee. Diagnostic Use of Prosomatostatin, 2012.
Brazeau P, Vale W, Burgus R, Ling N, Butcher M, Rivier J, et al: Hypothalamic polypeptide that inhibits the secretion of immunoreactive pituitary growth hormone. Science 1973;179:77-79.
Lin TM, Evans DC, Shaar CJ, Root MA: Action of somatostatin on stomach, pancreas, gastric mucosal blood flow, and hormones. Am J Physiol 1983;244:G40-G45.
Bissette G, Myers B: Somatostatin in Alzheimer's disease and depression. Life Sci 1992;51:1389-1410.
Johansson O, Hokfelt T, Elde RP: Immunohistochemical distribution of somatostatin-like immunoreactivity in the central nervous system of the adult rat. Neuroscience 1984;13:265-339.
Foy CJ, Ardill J, Filmore D, Lawson JT, Passmore AP: Plasma somatostatin and gastrointestinal peptides in Alzheimer's disease and vascular dementia. QJM 2001;94:631-635.
Lundqvist G, Gustavsson S, Elde R, Arimura A: A radioimmunoabsorbent assay for plasma somatostatin. Clin Chim Acta 1980;101:183-191.
Lucey MR, Fairclough PD, Wass JA, Kwasowski P, Medbak S, Webb J, et al: Response of circulating somatostatin, insulin, gastrin and GIP, to intraduodenal infusion of nutrients in normal man. Clin Endocrinol (Oxf) 1984;21:209-217.
Strazzulla G, Guazzelli R, Romano S, Matassi L, Cotrozzi G, Brocchi A: Circadian variations of plasma somatostatin levels in healthy subjects. Chronobiologia 1990;17:219-225.
van Dijk PR, Landman GW, van Essen L, Struck J, Groenier KH, Bilo HJ, et al: The relationship between N-terminal prosomatostatin, all-cause and cardiovascular mortality in patients with type 2 diabetes mellitus (ZODIAC-35). BMC Endocr Disord 2015;15:19.
Kalmijn S, Mehta KM, Pols HA, Hofman A, Drexhage HA, Breteler MM: Subclinical hyperthyroidism and the risk of dementia. The Rotterdam study. Clin Endocrinol (Oxf) 2000;53:733-737.
Martocchia A, Stefanelli M, Falaschi GM, Toussan L, Ferri C, Falaschi P: Recent advances in the role of cortisol and metabolic syndrome in age-related degenerative diseases. Aging Clin Exp Res 2016;28:17-23.
Cordoba-Chacon J, Gahete MD, Castano JP, Kineman RD, Luque RM: Somatostatin and its receptors contribute in a tissue-specific manner to the sex-dependent metabolic (fed/fasting) control of growth hormone axis in mice. Am J Physiol Endocrinol Metab 2011;300:E46-E54.
Nagaya N, Mori H, Murakami S, Kangawa K, Kitamura S: Adrenomedullin: angiogenesis and gene therapy. Am J Physiol Regul Integr Comp Physiol 2005;288:R1432-R1437.
Dahl A, Berg S, Nilsson SE: Identification of dementia in epidemiological research: a study on the usefulness of various data sources. Aging Clin Exp Res 2007;19:381-389.
Jin YP, Gatz M, Johansson B, Pedersen NL: Sensitivity and specificity of dementia coding in two Swedish disease registries. Neurology 2004;63:739-741.
Copyright / Drug Dosage / Disclaimer
Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher.
Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.
You do not currently have access to this content.