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Salivary Alpha-Amylase Activity and Mild Cognitive Impairment among Japanese Older Adults: The Toon Health Study

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Abstract

Background

There is growing interest in examining objective markers for early identification and behavioral intervention to prevent dementia and mild cognitive impairment in clinical and community settings.

Objective

To investigate the association between salivary alpha-amylase as an objective measure of psychological stress response and mild cognitive impairment for the implication of psychological stress in the development of mild cognitive impairment.

Design, Setting, and Participants

This cross-sectional study involved 865 participants aged ≥ 65 years. A saliva sample was collected in the morning, and the levels of salivary alpha-amylase were assayed. Mild cognitive impairment was evaluated using the Japanese version of the Montreal Cognitive Assessment; a score < 26 was indicative of mild cognitive impairment. A multivariable logistic regression model was used to examine the association of salivary alpha-amylase and mild cognitive impairment after adjusting for age, sex, current drinking status, current smoking status, body mass index, hypertension, diabetes mellitus, physical activity, education, social support, social network, and heart rate variability.

Results

Salivary alpha-amylase was associated with mild cognitive impairment (the multivariable-adjusted odds ratio [95% confidence interval] for the 1-standard deviation increment of log-transformed salivary alpha-amylase was 1.24 [1.07–1.44]). This significant association persisted after adjusting for various confounding factors.

Conclusion

Elevation of salivary alpha-amylase was associated with mild cognitive impairment among Japanese community-dwelling older adults. This suggests that salivary alpha-amylase is a useful objective marker of psychological stress responses associated with mild cognitive impairment.

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References

  1. World Health Organization (2021) Dementia. https://www.who.int/news-room/fact-sheets/detail/dementia. Last updated 2 September 2021, Accessed on 11 December 2021.

  2. Gauthier S, Reisberg B, Zaudig M, Petersen RC, Ritchie K, Broich K, et al. International Psychogeriatric Association Expert Conference on mild cognitive impairment. Lancet. 2006;367(9518):1262–1270. doi:https://doi.org/10.1016/S0140-6736(06)68542-5.

    Article  Google Scholar 

  3. Petersen RC, Smith GE, Waring SC, Ivnik RJ, Tangalos EG, Kokmen E. Mild cognitive impairment: clinical characterization and outcome. Arch Neurol. 1999;56(3):303–308. doi:https://doi.org/10.1001/archneur.56.3.303

    Article  CAS  Google Scholar 

  4. Livingston G, Huntley J, Sommerlad A, Ames D, Ballard C, Banerjee S, et al. Dementia prevention, intervention, and care: 2020 report of the Lancet Commission. Lancet. 2020;396(10248):413–446. doi:https://doi.org/10.1016/S0140-6736(20)30367-6.

    Article  Google Scholar 

  5. Freire ACC, Pondé MP, Liu A, Caron J. Anxiety and depression as longitudinal predictors of mild cognitive impairment in older adults. Can J Psychiatry. 2017;62(5):343–350. doi:https://doi.org/10.1177/0706743717699175

    Article  Google Scholar 

  6. Wilson RS, Schneider JA, Boyle PA, Arnold SE, Tang Y, Bennett DA. Chronic distress and incidence of mild cognitive impairment. Neurology. 2007;68(24):2085–2092. doi:https://doi.org/10.1212/01.wnl.0000264930.97061.82

    Article  CAS  Google Scholar 

  7. Johansson L, Guo X, Waern M, Ostling S, Gustafson D, Bengtsson C, et al. Midlife psychological stress and risk of dementia: a 35-year longitudinal population study. Brain. 2010;133(Pt 8):2217–2224. doi:https://doi.org/10.1093/brain/awq116

    Article  Google Scholar 

  8. Binder EB, Nemeroff CB. The CRF system, stress, depression and anxiety-insights from human genetic studies. Mol Psychiatry. 2010;15(6):574–588. doi:https://doi.org/10.1038/mp.2009.141

    Article  CAS  Google Scholar 

  9. Cohen S, Janicki-Deverts D, Miller GE. Psychological stress and disease. JAMA. 2007;298(14):1685–1687. doi:https://doi.org/10.1001/jama.298.14.1685

    Article  CAS  Google Scholar 

  10. Hackett RA Steptoe A. Type 2 diabetes mellitus and psychological stress — a modifiable risk factor. Nat Rev Endocrinol. 2017;13(9):547–560. doi:https://doi.org/10.1038/nrendo.2017.64

    Article  Google Scholar 

  11. Lupien S, Lecours AR, Lussier I, Schwartz G, Nair NP, Meaney MJ. Basal cortisol levels and cognitive deficits in human aging. J Neurosci. 1994;14(5 Pt 1):2893–2903. doi:https://doi.org/10.1523/JNEUROSCI.14-05-02893.1994

    Article  CAS  Google Scholar 

  12. Lind K, Edman A, Nordlund A, Olsson T, Wallin A. Increased saliva cortisol awakening response in patients with mild cognitive impairment. Dement Geriatr Cogn Disord. 2007;24(5):389–395. doi:https://doi.org/10.1159/000109938

    Article  Google Scholar 

  13. Venero C, Díaz-Mardomingo C, Pereda-Pérez I, García-Herranz S, Utrera L, Valencia A, et al. Increased morning salivary cortisol levels in older adults with nonamnestic and multidomain mild cognitive impairment. Psychoneuroendocrinology. 2013;38(4):488–498. doi:https://doi.org/10.1016/j.psyneuen.2012.07.007

    Article  CAS  Google Scholar 

  14. Nicolini P, Ciulla MM, Malfatto G, Abbate C, Mari D, Rossi PD, et al. Autonomic dysfunction in mild cognitive impairment: evidence from power spectral analysis of heart rate variability in a cross-sectional case-control study. PLoS One. 2014;9(5):e96656. Published 2014 May 6. doi:https://doi.org/10.1371/journal.pone.0096656

    Article  Google Scholar 

  15. Collins O, Dillon S, Finucane C, Lawlor B, Kenny RA. Parasympathetic autonomic dysfunction is common in mild cognitive impairment. Neurobiol Aging. 2012;33(10):2324–2333. doi:https://doi.org/10.1016/j.neurobiolaging.2011.11.017

    Article  Google Scholar 

  16. Nater UM, Rohleder N. Salivary alpha-amylase as a non-invasive biomarker for the sympathetic nervous system: current state of research. Psychoneuroendocrinology. 2009;34(4):486–496. doi:https://doi.org/10.1016/j.psyneuen.2009.01.014

    Article  CAS  Google Scholar 

  17. Yu NN, Wang XX, Yu JT, Wang ND, Lu RC, Miao D, et al. Blocking beta2-adrenergic receptor attenuates acute stress-induced amyloid beta peptides production. Brain Res. 2010;1317:305–310. doi:https://doi.org/10.1016/j.brainres.2009.12.087

    Article  CAS  Google Scholar 

  18. Ni Y, Zhao X, Bao G, Zou L, Teng L, Wang Z, et al. Activation of beta2-adrenergic receptor stimulates gamma-secretase activity and accelerates amyloid plaque formation. Nat Med. 2006;12(12):1390–1396. doi:https://doi.org/10.1038/nm1485.

    Article  CAS  Google Scholar 

  19. Tanzi RE. The synaptic Abeta hypothesis of Alzheimer disease. Nat Neurosci. 2005;8(8):977–979. doi:https://doi.org/10.1038/nn0805-977

    Article  CAS  Google Scholar 

  20. Saito I, Maruyama K, Eguchi E, Kato T, Kawamura R, Takata Y, et al. Low heart rate variability and sympathetic dominance modifies the association between insulin resistance and metabolic syndrome — the toon health study. Circ J. 2017;81(10):1447–1453. doi:https://doi.org/10.1253/circj.CJ-17-0192

    Article  Google Scholar 

  21. Fujiwara Y, Suzuki H, Yasunaga M, Sugiyama M, Ijuin M, Sakuma N, et al. Brief screening tool for mild cognitive impairment in older Japanese: validation of the Japanese version of the Montreal Cognitive Assessment. Geriatr Gerontol Int. 2010;10(3):225–232. doi:https://doi.org/10.1111/j.1447-0594.2010.00585.x

    Article  Google Scholar 

  22. Waldron-Perrine B, Gabel NM, Seagly K, Kraal AZ, Pangilinan P, Spencer RJ, et al. Montreal Cognitive Assessment as a screening tool: Influence of performance and symptom validity. Neurol Clin Pract. 2019;9(2):101–108. doi:https://doi.org/10.1212/CPJ.0000000000000604

    Article  Google Scholar 

  23. Vaglio J Jr, Conard M, Poston WS, O’Keefe J, Haddock CK, House J, et al. Testing the performance of the ENRICHD Social Support Instrument in cardiac patients. Health Qual Life Outcomes. 2004;2:24. Published 2004 May 13. doi:https://doi.org/10.1186/1477-7525-2-24

    Article  Google Scholar 

  24. Berkman LF, Syme SL. Social networks, host resistance, and mortality: a nine-year follow-up study of Alameda County residents. Am J Epidemiol. 1979;109(2):186–204. doi:https://doi.org/10.1093/oxfordjournals.aje.a112674

    Article  CAS  Google Scholar 

  25. Ishikawa-Takata K, Naito Y, Tanaka S, Ebine N, Tabata I. Use of doubly labeled water to validate a physical activity questionnaire developed for the Japanese population. J Epidemiol. 2011;21(2):114–121. doi:https://doi.org/10.2188/jea.je20100079

    Article  Google Scholar 

  26. McEwen BS. Protective and damaging effects of stress mediators: central role of the brain. Dialogues Clin Neurosci. 2006;8(4):367–381. doi:https://doi.org/10.31887/DCNS.2006.8.4/bmcewen

    Article  Google Scholar 

  27. Byman E, Schultz N, Netherlands Brain Bank, Blom AM, Wennström M. A Potential Role for α-Amylase in Amyloid-β-Induced Astrocytic Glycogenolysis and Activation. J Alzheimers Dis. 2019;68(1):205–217. doi:https://doi.org/10.3233/JAD-180997

    Article  CAS  Google Scholar 

  28. Luong Kv, Nguyen LT. The role of Beta-adrenergic receptor blockers in Alzheimer’s disease: potential genetic and cellular signaling mechanisms. Am J Alzheimers Dis Other Demen. 2013;28(5):427–439. doi:https://doi.org/10.1177/1533317513488924

    Article  Google Scholar 

  29. Gorelick PB, Scuteri A, Black SE, Decarli C, Greenberg SM, Iadecola C, et al. Vascular contributions to cognitive impairment and dementia: a statement for healthcare professionals from the american heart association/american stroke association. Stroke. 2011;42(9):2672–2713. doi:https://doi.org/10.1161/STR.0b013e3182299496

    Article  Google Scholar 

  30. Nation DA, Hong S, Jak AJ, Delano-Wood L, Mills PJ, Bondi MW, et al. Stress, exercise, and Alzheimer’s disease: a neurovascular pathway. Med Hypotheses. 2011;76(6):847–854. doi:https://doi.org/10.1016/j.mehy.2011.02.034

    Article  CAS  Google Scholar 

  31. Ali N, Nater UM. Salivary Alpha-Amylase as a Biomarker of Stress in Behavioral Medicine. International Journal of Behavioral Medicine. 2020;27(3):337–342. doi:https://doi.org/10.1007/s12529-019-09843-x.

    Article  Google Scholar 

  32. Booij SH, Bos EH, Bouwmans MEJ, et al. Cortisol and α-Amylase Secretion Patterns between and within Depressed and Non-Depressed Individuals. PloS One. 2015;10(7), e0131002. doi:https://doi.org/10.1371/journal.pone.0131002.

    Article  Google Scholar 

  33. Nater UM, La Marca R, Florin L, et al. Stress-induced changes in human salivary alpha-amylase activity — associations with adrenergic activity. Psychoneuroendocrinology. 2006;31(1), 49–58. doi:https://doi.org/10.1016/j.psyneuen.2005.05.010.

    Article  CAS  Google Scholar 

  34. Mangialasche F, Kivipelto M, Solomon A, Fratiglioni L. Dementia prevention: current epidemiological evidence and future perspective. Alzheimers Res Ther. 2012;4(1):6. Published 2012 Feb 13. doi:https://doi.org/10.1186/alzrt104

    Article  Google Scholar 

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Acknowledgments

The authors thank all the participants and staff members of the Toon Health Study for their substantial contribution.

Funding

Funding: This study was supported by JSPS KAKENHI Grant Numbers; JP16K09072, JP17KK0175, JP19K10670, 25293142, and 8020 Promotion Foundation, Japan in 2016, 2017. The sponsors had no role in the design and conduct of the study; in the collection, analysis, and interpretation of data; in the preparation of the manuscript; or in the review or approval of the manuscript.

Author information

Authors and Affiliations

  1. Department of Public Health, Juntendo University Faculty of Medicine, Tokyo, Japan

    N. Yamane, A. Ikeda & K. Tomooka

  2. Department of Public Health and Epidemiology, Faculty of Medicine, Oita University, Yufu, Japan

    I. Saito

  3. Laboratory of Community Health and Nutrition, Special Course of Food and Health Science, Department of Bioscience, Graduate School of Agriculture, Ehime University, Toon, Japan

    K. Maruyama

  4. Department of Epidemiology, Fukushima Medical University School of Medicine, Fukushima City, Japan

    E. Eguchi

  5. Department of Community Health Systems Nursing, Graduate School of Medicine, Ehime University, Toon, Japan

    K. Suyama, A. Fujii, T. Shiba & A. Kooka

  6. Faculty of Nursing, Shijonawate Gakuen University, Osaka, Japan

    K. Tanaka

  7. Department of Nursing, Faculty of Human Health and Welfare, St. Catherine University, Matsuyama City, Japan

    S. Nakamura & M. Kajita

  8. Department of Diabetes and Molecular Genetics, Graduate School of Medicine, Ehime University, Toon, Japan

    R. Kawamura, Y. Takata & H. Osawa

  9. Department of Behavioural Science and Health, University College London, London, UK

    A. Steptoe

  10. Department of Public Health, Juntendo University Graduate School of Medicine, 2-1-1 Hongo, Bunkyo-ku, Tokyo, 113-8421, Japan

    Takeshi Tanigawa

Authors
  1. N. Yamane
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  2. A. Ikeda
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  5. K. Maruyama
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  8. A. Fujii
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  9. T. Shiba
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  10. K. Tanaka
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  15. Y. Takata
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  16. H. Osawa
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  17. A. Steptoe
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  18. Takeshi Tanigawa
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Corresponding author

Correspondence to Takeshi Tanigawa.

Ethics declarations

Conflict of Interest: Dr. Ikeda reports grants from JSPS KAKENHI, during the conduct of the study. Dr. Saito reports grants from 8020 Promotion Foundation, during the conduct of the study. Dr. Tanigawa reports grants from JSPS KAKENHI, during the conduct of the study. The other authors have nothing to disclose.

Ethical standards: This study was approved by the Institutional Review Board of Ehime University Hospital, Toon, Japan and the Ethics Committee of Juntendo University, Tokyo, Japan.

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Yamane, N., Ikeda, A., Tomooka, K. et al. Salivary Alpha-Amylase Activity and Mild Cognitive Impairment among Japanese Older Adults: The Toon Health Study. J Prev Alzheimers Dis 9, 752–757 (2022). https://doi.org/10.14283/jpad.2022.51

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  • DOI: https://doi.org/10.14283/jpad.2022.51

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