Depression and Plasma Biomarkers of Alzheimer’s Disease in a Diverse Community Cohort: The Impact of Ethnicity and Level of Depression
Main Article Content
Abstract
Background: Depression is both a risk factor for and early symptom of Alzheimer’s disease. Numerous studies have investigated the relationship between AT(N) biomarkers of AD and depression; however, the majority of these have utilized CSF in Non-Hispanic White populations.
Objective: To investigate the relationship between plasma total Tau, Aβ40, Aβ42, NFL and depression in Mexican-Americans and Non-Hispanic Whites.
Methods: The study was a cross-sectional comparison of 645 Mexican American and 644 Non-Hispanic White older adults in a community-based study of cognitive aging who had been categorized as having unimpaired cognition using a consensus based algorithmic approach. Plasma biomarkers were assayed using Simoa technology. The Geriatric Depression Scale assessed depression.
Results: Mexican Americans had significantly higher scores on the GDS. Non-Hispanic Whites had higher Aβ40, and Aβ42 and MAs had higher NFL and Tau. For Mexican Americans, linear regression analyses found NfL and Aβ42 significant predictors of GDS scores whereas for the Non-Hispanic White group none of the biomarkers was significantly related to GDS total score or any of the subscale scores. Those scoring in the depressed range had significantly higher levels of Aβ40, Aβ42, and NFL. When analyzed by ethnicity the depressed Mexican Americans had significantly higher levels of Aβ40, Aβ42, and NFL than the non-depressed. No difference between the depression levels on any of the biomarkers was found for Non-Hispanic Whites.
Conclusions: Findings support the importance of evaluating the effect of ethnicity and level of depressive symptoms when assessing the relationship of AD biomarkers to depression. In cognitively unimpaired MAs depression is related to the Alzheimer’s Disease biomarkers but this is not the case for Non-Hispanic Whites. Higher levels of these biomarkers among depressed cognitively unimpaired Mexican Americans may be an indicator of increased risk for cognitive impairment but not for Non-Hispanic Whites. Longitudinal research is needed to clarify the effect of ethnicity on the biomarker-depression relationship.
Keywords:
Plasma Biomarkers, Alzheimer’s, Depression, Ethnicity
Article Details
How to Cite
HALL, James R. et al.
Depression and Plasma Biomarkers of Alzheimer’s Disease in a Diverse Community Cohort: The Impact of Ethnicity and Level of Depression.
Medical Research Archives, [S.l.], v. 11, n. 1, jan. 2023.
ISSN 2375-1924.
Available at: <https://esmed.org/MRA/mra/article/view/3466>. Date accessed: 03 dec. 2024.
doi: https://doi.org/10.18103/mra.v11i1.3466.
Section
Research Articles
The Medical Research Archives grants authors the right to publish and reproduce the unrevised contribution in whole or in part at any time and in any form for any scholarly non-commercial purpose with the condition that all publications of the contribution include a full citation to the journal as published by the Medical Research Archives.
References
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26. McKnight-Eily LR, Okoro CA, Strine TW, et al. Racial and Ethnic Disparities in the Prevalence of Stress and Worry, Mental Health Conditions, and Increased Substance Use Among Adults During the COVID-19 Pandemic - United States, April and May 2020. MMWR Morb Mortal Wkly Rep. 2021;70(5):162-166. Published 2021 Feb 5. doi:10.15585/mmwr.mm7005a3
27. Babulal GM, Quiroz YT, Albensi BC, et al. Perspectives on ethnic and racial disparities in Alzheimer's disease and related dementias: Update and areas of immediate need. Alzheimers Dement. 2019;15(2):292-312. doi:10.1016/j.jalz.2018.09.009
28. Barnes LL. Biomarkers for Alzheimer Dementia in Diverse Racial and Ethnic Minorities-A Public Health Priority. JAMA Neurol. 2019;76(3):251-253. doi:10.1001/jamaneurol.2018.3444
29. O'Bryant SE, Johnson LA, Barber RC, et al. The Health & Aging Brain among Latino Elders (HABLE) study methods and participant characteristics. Alzheimers Dement (Amst). 2021;13(1):e12202. Published 2021 Jun 21. doi:10.1002/dad2.12202
30. Institute for Translational Research. Accessed March 19, 2022. https://apps.unthsc.edu/itr/
31. Yesavage JA, Brink TL, Rose TL, et al. Development and validation of a geriatric depression screening scale: a preliminary report. J Psychiatr Res. 1982;17(1):37-49. doi:10.1016/0022-3956(82)90033-4
32. Hall, J.R., O’Bryant, S.E., Johnson, L.A. & Barber, R. Depressive Symptom Clusters and Neuropsychological Performance in Mild Alzheimer’s and Cognitively Intact Elderly. Journal of Depression Research and Treatment, vol. 2011, 2011, Article ID 396958, 6 pp. doi:10.1155/2011/396958.
33. O'Bryant SE, Waring SC, Cullum CM, et al. Staging dementia using Clinical Dementia Rating Scale Sum of Boxes scores: a Texas Alzheimer's research consortium study. Arch Neurol. 2008 Aug;65(8):1091-5. doi: 10.1001/archneur.65.8.1091. PMID: 18695059; PMCID: PMC3409562.
34. O'Bryant SE, Gupta V, Henriksen K, et al. Guidelines for the standardization of preanalytic variables for blood-based biomarker studies in Alzheimer's disease research. Alzheimers Dement. 2015 May;11(5):549-60.
doi: 10.1016/j.jalz.2014.08.099.
35. Johansson M, Stomrud E, Johansson PM, et al. Development of Apathy, Anxiety, and Depression in Cognitively Unimpaired Older Adults: Effects of Alzheimer's Disease Pathology and Cognitive Decline. Biol Psychiatry. 2022;92(1):34-43. doi:10.1016/j.biopsych.2022.01.012
36. Donovan NJ, Locascio JJ, Marshall GA, et al. Longitudinal Association of Amyloid Beta and Anxious-Depressive Symptoms in Cognitively Normal Older Adults. Am J Psychiatry. 2018;175(6):530-537. doi:10.1176/appi.ajp.2017.17040442
37. Chen MH, Liu YL, Kuo HW, et al. Neurofilament Light Chain Is a Novel Biomarker for Major Depression and Related Executive Dysfunction. Int J Neuropsychopharmacol. 2022;25(2):99-105. doi:10.1093/ijnp/pyab068
36. O’Bryant SE, Johnson L, Reisch J, et al. Risk factors for mild cognitive impairment among Mexican Americans. Alzheimers Dement. 2013;9:622–31.e1. [PubMed: 23643456]
37. O’Bryant SE, Johnson L, Balldin V, et al. Characterization of Mexican Americans with mild cognitive impairment and Alzheimer’s disease. J AlzheimersDis. 2013;33:373–9
38. O'Bryant SE, Barber RC, Philips N, et al. The Link between APOE4 Presence and Neuropsychological Test Performance among Mexican Americans and Non-Hispanic Whites of the Multiethnic Health & Aging Brain Study - Health Disparities Cohort. Dement Geriatr Cogn Disord. 2022;51(1):26-31. doi:10.1159/000521898
39. Burns RA, Andrews S, Cherbuin N, Anstey KJ. Role of apolipoprotein E epsilon 4 (APOE*ε4) as an independent risk factor for incident depression over a 12-year period in cognitively intact adults across the lifespan. BJPsych Open. 2020;6(3):e47. Published 2020 May 8. doi:10.1192/bjo.2020.29
40. Chan CK, Soldan A, Pettigrew C, et al. Depressive symptoms and CSF Alzheimer's disease biomarkers in relation to clinical symptom onset of mild cognitive impairment. Alzheimers Dement (Amst). 2020;12(1):e12106. Published 2020 Sep 24. doi:10.1002/dad2.12106
41. Moriguchi S, Takahata K, Shimada H, et al. Excess tau PET ligand retention in elderly patients with major depressive disorder. Mol Psychiatry. 2021;26(10):5856-5863. doi:10.1038/s41380-020-0766-9
42. Babulal GM, Roe CM, Stout SH, et al. Depression is Associated with Tau and Not Amyloid Positron Emission Tomography in Cognitively Normal Adults. J Alzheimers Dis. 2020;74(4):1045-1055. doi:10.3233/JAD-191078
2. Steenland K, Karnes C, Seals R, Carnevale C, Hermida A, Levey A. Late-life depression as a risk factor for mild cognitive impairment or Alzheimer's disease in 30 US Alzheimer's disease centers. J Alzheimers Dis. 2012;31(2):265-275. doi:10.3233/JAD-2012-111922
3. Ownby RL, Crocco E, Acevedo A, John V, Loewenstein D. Depression and risk for Alzheimer disease: systematic review, meta-analysis, and metaregression analysis. Arch Gen Psychiatry. 2006;63(5):530-538. doi:10.1001/archpsyc.63.5.530
4. Diniz BS, Butters MA, Albert SM, Dew MA, Reynolds CF 3rd. Late-life depression and risk of vascular dementia and Alzheimer's disease: systematic review and meta-analysis of community-based cohort studies. Br J Psychiatry. 2013;202(5):329-335. doi:10.1192/bjp.bp.112.118307
5. Donovan NJ, Amariglio RE, Zoller AS, et al. Subjective cognitive concerns and neuropsychiatric predictors of progression to the early clinical stages of Alzheimer disease. Am J Geriatr Psychiatry. 2014;22(12):1642-1651. doi:10.1016/j.jagp.2014.02.007
6. Hall, JR, O’Bryant, SE, Johnson, L & Barber, RC. Depression and Brain-derived Neurotrophic Factor levels in Alzheimer’s disease. Neuroscience and Medicine;2011: 2: 1, 43-47.
7. Matsushima J, Kawashima T, Nabeta H, et al. Association of inflammatory biomarkers with depressive symptoms and cognitive decline in a community-dwelling healthy older sample: a 3-year follow-up study. J Affect Disord. 2015 Mar 1;173:9-14. doi: 10.1016/j.jad.2014.10.030. Epub 2014 Oct 22. PMID: 25462389.
8. Wenzler S, Knochel C, Balaban C, et al. Integrated Biomarkers for Depression in Alzheimer's Disease: A Critical Review. Curr Alzheimer Res. 2017;14(4):441-452. doi:10.2174/1567205013666160603011256
9. Liguori C, Pierantozzi M, Chiaravalloti A, et al. When Cognitive Decline and Depression Coexist in the Elderly: CSF Biomarkers Analysis Can Differentiate Alzheimer's Disease from Late-Life Depression. Front Aging Neurosci. 2018 Feb 23;10:38. doi: 10.3389/fnagi.2018.00038. PMID: 29527163; PMCID: PMC5829060.
10. Zhang Z, Wei F, Shen XN, et al. Alzheimer's Disease Neuroimaging Initiative. Associations of Subsyndromal Symptomatic Depression with Cognitive Decline and Brain Atrophy in Elderly Individuals without Dementia: A Longitudinal Study. J Affect Disord. 2020 Sep 1;274:262-268. doi: 10.1016/j.jad.2020.05.097. Epub 2020 May 23. PMID: 32469814.
11. Jack CR Jr, Bennett DA, Blennow K, et al. NIA-AA Research Framework: Toward a biological definition of Alzheimer's disease. Alzheimers Dement. 2018;14(4):535-562. doi:10.1016/j.jalz.2018.02.018
12. Pomara N, Bruno D, Sarreal AS, et al. Lower CSF amyloid beta peptides and higher F2-isoprostanes in cognitively intact elderly individuals with major depressive disorder. Am J Psychiatry. 2012 May;169(5):523-30. doi: 10.1176/appi.ajp.2011.11081153. PMID: 22764362
13. Gudmundsson P, Skoog I, Waern M, et al. The relationship between cerebrospinal fluid biomarkers and depression in elderly women. Am J Geriatr Psychiatry. 2007;15(10):832-838. doi:10.1097/JGP.0b013e3180547091
14. Gudmundsson P, Skoog I, Waern M, et al. Is there a CSF biomarker profile related to depression in elderly women?. Psychiatry Res. 2010;176(2-3):174-178. doi:10.1016/j.psychres.2008.11.012
15. Johansson M, Stomrud E, Johansson PM, et al. Development of Apathy, Anxiety, and Depression in Cognitively Unimpaired Older Adults: Effects of Alzheimer's Disease Pathology and Cognitive Decline [published online ahead of print, 2022 Jan 31]. Biol Psychiatry. 2022;S0006-3223(22)00053-1. doi:10.1016/j.biopsych.2022.01.012
16. Gonzales MM, Insel PS, Nelson C, et al. Alzheimer's Disease Neuroimaging Initiative. Chronic depressive symptomatology and CSF amyloid beta and tau levels in mild cognitive impairment. Int J Geriatr Psychiatry. 2018 Oct;33(10):1305-1311. doi: 10.1002/gps.4926. Epub 2018 Jun 28. PMID: 29953668.
17. Xu W, Feng W, Shen XN, et al. Alzheimer’s Disease Neuroimaging Initiative, Yu JT. Amyloid Pathologies Modulate the Associations of Minimal Depressive Symptoms With Cognitive Impairments in Older Adults Without Dementia. Biol Psychiatry. 2020 Jul 15:S0006-3223(20)31742-X. doi: 10.1016/j.biopsych.2020.07.004. Epub ahead of print. PMID: 32980133.
18. Hall JR, Petersen M, Johnson LA and O’Bryant S. Level of plasma tau and depression, anxiety and worry in cognitively normal adults. Alzheimer’s Dement. 2020, 16:e039495. https://doi.org/10.1002/alz.039495
19. Babulal GM, Roe CM, Stout SH, et al. Depression is Associated with Tau and Not Amyloid Positron Emission Tomography in Cognitively Normal Adults. J Alzheimers Dis. 2020;74(4):1045-1055. doi:10.3233/JAD-191078
20. Yamazaki C, Tamaoki T, Nunomura A, Tamai K, Yasuda K, Motohashi N. Plasma Amyloid-β and Alzheimer's Disease-Related Changes in Late-Life Depression. J Alzheimers Dis. 2017;58(2):349-354. doi:10.3233/JAD-170111
21. Banning LCP, Ramakers IHGB, Rosenberg PB, Lyketsos CG, Leoutsakos JS; Alzheimer's Disease Neuroimaging Initiative. Alzheimer's disease biomarkers as predictors of trajectories of depression and apathy in cognitively normal individuals, mild cognitive impairment, and Alzheimer's disease dementia. Int J Geriatr Psychiatry. 2021;36(1):224-234. doi:10.1002/gps.5418
22. Banning LCP, Ramakers IHGB, Deckers K, Verhey FRJ, Aalten P. Affective symptoms and AT(N) biomarkers in mild cognitive impairment and Alzheimer's disease: A systematic literature review. Neurosci Biobehav Rev. 2019 Dec;107:346-359. doi: 10.1016/j.neubiorev.2019.09.014. Epub 2019 Sep 13. PMID: 31525387.
23. U.S. Census Bureau QuickFacts: United States. https://www.census. gov/quickfacts/fact/table/US/PST045219. Accessed December 8, 2020.
24. Pew Research Center [Internet]. How the Hispanic Population is Changing? [Cited 2020 March 10]. Available from: https://www.pewresearch.org/fact-tank/2017/09/18/how-the-u-s-hispanic-population-is- changing/
25. Mehta KM, Yeo GW. Systematic review of dementia prevalence and incidence in United States race/ethnic populations. Alzheimers Dement. 2017 Jan;13(1):72-83. doi: 10.1016/j.jalz.2016.06.2360. Epub 2016 Sep 4. PMID: 27599209
26. McKnight-Eily LR, Okoro CA, Strine TW, et al. Racial and Ethnic Disparities in the Prevalence of Stress and Worry, Mental Health Conditions, and Increased Substance Use Among Adults During the COVID-19 Pandemic - United States, April and May 2020. MMWR Morb Mortal Wkly Rep. 2021;70(5):162-166. Published 2021 Feb 5. doi:10.15585/mmwr.mm7005a3
27. Babulal GM, Quiroz YT, Albensi BC, et al. Perspectives on ethnic and racial disparities in Alzheimer's disease and related dementias: Update and areas of immediate need. Alzheimers Dement. 2019;15(2):292-312. doi:10.1016/j.jalz.2018.09.009
28. Barnes LL. Biomarkers for Alzheimer Dementia in Diverse Racial and Ethnic Minorities-A Public Health Priority. JAMA Neurol. 2019;76(3):251-253. doi:10.1001/jamaneurol.2018.3444
29. O'Bryant SE, Johnson LA, Barber RC, et al. The Health & Aging Brain among Latino Elders (HABLE) study methods and participant characteristics. Alzheimers Dement (Amst). 2021;13(1):e12202. Published 2021 Jun 21. doi:10.1002/dad2.12202
30. Institute for Translational Research. Accessed March 19, 2022. https://apps.unthsc.edu/itr/
31. Yesavage JA, Brink TL, Rose TL, et al. Development and validation of a geriatric depression screening scale: a preliminary report. J Psychiatr Res. 1982;17(1):37-49. doi:10.1016/0022-3956(82)90033-4
32. Hall, J.R., O’Bryant, S.E., Johnson, L.A. & Barber, R. Depressive Symptom Clusters and Neuropsychological Performance in Mild Alzheimer’s and Cognitively Intact Elderly. Journal of Depression Research and Treatment, vol. 2011, 2011, Article ID 396958, 6 pp. doi:10.1155/2011/396958.
33. O'Bryant SE, Waring SC, Cullum CM, et al. Staging dementia using Clinical Dementia Rating Scale Sum of Boxes scores: a Texas Alzheimer's research consortium study. Arch Neurol. 2008 Aug;65(8):1091-5. doi: 10.1001/archneur.65.8.1091. PMID: 18695059; PMCID: PMC3409562.
34. O'Bryant SE, Gupta V, Henriksen K, et al. Guidelines for the standardization of preanalytic variables for blood-based biomarker studies in Alzheimer's disease research. Alzheimers Dement. 2015 May;11(5):549-60.
doi: 10.1016/j.jalz.2014.08.099.
35. Johansson M, Stomrud E, Johansson PM, et al. Development of Apathy, Anxiety, and Depression in Cognitively Unimpaired Older Adults: Effects of Alzheimer's Disease Pathology and Cognitive Decline. Biol Psychiatry. 2022;92(1):34-43. doi:10.1016/j.biopsych.2022.01.012
36. Donovan NJ, Locascio JJ, Marshall GA, et al. Longitudinal Association of Amyloid Beta and Anxious-Depressive Symptoms in Cognitively Normal Older Adults. Am J Psychiatry. 2018;175(6):530-537. doi:10.1176/appi.ajp.2017.17040442
37. Chen MH, Liu YL, Kuo HW, et al. Neurofilament Light Chain Is a Novel Biomarker for Major Depression and Related Executive Dysfunction. Int J Neuropsychopharmacol. 2022;25(2):99-105. doi:10.1093/ijnp/pyab068
36. O’Bryant SE, Johnson L, Reisch J, et al. Risk factors for mild cognitive impairment among Mexican Americans. Alzheimers Dement. 2013;9:622–31.e1. [PubMed: 23643456]
37. O’Bryant SE, Johnson L, Balldin V, et al. Characterization of Mexican Americans with mild cognitive impairment and Alzheimer’s disease. J AlzheimersDis. 2013;33:373–9
38. O'Bryant SE, Barber RC, Philips N, et al. The Link between APOE4 Presence and Neuropsychological Test Performance among Mexican Americans and Non-Hispanic Whites of the Multiethnic Health & Aging Brain Study - Health Disparities Cohort. Dement Geriatr Cogn Disord. 2022;51(1):26-31. doi:10.1159/000521898
39. Burns RA, Andrews S, Cherbuin N, Anstey KJ. Role of apolipoprotein E epsilon 4 (APOE*ε4) as an independent risk factor for incident depression over a 12-year period in cognitively intact adults across the lifespan. BJPsych Open. 2020;6(3):e47. Published 2020 May 8. doi:10.1192/bjo.2020.29
40. Chan CK, Soldan A, Pettigrew C, et al. Depressive symptoms and CSF Alzheimer's disease biomarkers in relation to clinical symptom onset of mild cognitive impairment. Alzheimers Dement (Amst). 2020;12(1):e12106. Published 2020 Sep 24. doi:10.1002/dad2.12106
41. Moriguchi S, Takahata K, Shimada H, et al. Excess tau PET ligand retention in elderly patients with major depressive disorder. Mol Psychiatry. 2021;26(10):5856-5863. doi:10.1038/s41380-020-0766-9
42. Babulal GM, Roe CM, Stout SH, et al. Depression is Associated with Tau and Not Amyloid Positron Emission Tomography in Cognitively Normal Adults. J Alzheimers Dis. 2020;74(4):1045-1055. doi:10.3233/JAD-191078