Resumen
Antecedentes: Los pacientes con depresión y deterioro cognitivo leve (DCL) tienen un alto riesgo de desarrollar demencia. La depresión implica un alto riesgo de ideación suicida (IS) e intentos de suicidio (AS). Los biomarcadores de la enfermedad de Alzheimer (EA) pueden clarificar el papel de la depresión e IS en la EA. Método: Cincuenta y nueve participantes >50 años con criterios de DCL-EA positivo (DCL-EA; 22) y negativo (DCL-NoEA; 24) y 13 controles sanos. La depresión fue evaluada con la Escala Geriátrica de Depresión (GDS-30) y la IS con el factor GDS-IS. Además, se midieron los siguientes biomarcadores en el líquido cefalorraquídeo: ß-amiloide (ß-A), tau hiperfosforilada (H-tau) y total (T-tau). Resultados: No se encontraron diferencias significativas entre los tres grupos de participantes en depresión o en IS. Sin embargo, en el grupo DCL-EA, niveles más bajos de H-tau y T-tau, indicadores de menor patología EA, se relacionaron significativamente con mayor riesgo de suicidio indirecto. Conclusiones: Este resultado subraya la importancia de considerar la IS en fases iniciales de EA, y el potencial papel de los biomarcadores de EA para detectar sus síntomas.
Citas
Albert, M. S., DeKosky, S. T., Dickson, D., Dubois, B., Feldman, H. H., Fox, N. C., Gamst, A., Holtzman, D. M., Jagust, W. J., Petersen, R. C., Snyder, P. J., Carrillo, M. C., Thies, B., & Phelps, C. H. (2011). The diagnosis of mild cognitive impairment due to Alzheimer’s disease: recommendations from the National Institute on Aging-Alzheimer’s Association workgroups on diagnostic guidelines for Alzheimer’s disease. Alzheimer’s & dementia: the journal of the Alzheimer’s Association, 7(3), 270–279. https://doi.org/10.1016/j.jalz.2011.03.008
Alejos, M., Vázquez-Bourgon, J., Santurtún, M., Riancho, J., & Santurtún, A. (2020). Do patients diagnosed with a neurological disease present increased risk of suicide? Neurologia, Article S0213-4853(20)30129-8. https://doi.org/10.1016/j.nrl.2020.03.003
Alphs, L., Brashear, H. R., Chappell, P., Conwell, Y., Dubrava, S., Khin, N. A., Kozauer, N., Hartley, D. M., Miller, D. S., Schindler, R. J., Siemers, E. R., Stewart, M., & Yaffe, K. (2016). Considerations for the assessment of suicidal ideation and behavior in older adults with cognitive decline and dementia. Alzheimer’s & Dementia, 2(1), 48–59. https://doi.org/10.1016/j.trci.2016.02.00
Atri, A. (2019). The Alzheimer’s disease clinical spectrum: Diagnosis and management. Medical Clinics, 103(2), 263-293. https://doi.org/10.1016/j.mcna.2018.10.009
Babulal, G. M., Ghoshal, N., Head, D., Vernon, E. K., Holtzman, D. M., Benzinger, T., Fagan, A. M., Morris, J. C., & Roe, C. M. (2016). Mood Changes in Cognitively Normal Older Adults are Linked to Alzheimer Disease Biomarker Levels. The American Journal of Geriatric Psychiatry, 24(11), 1095–1104. https://doi.org/10.1016/j.jagp.2016.04.004
Babulal, G. M., Roe, C. M., Stout, S. H., Rajasekar, G., Wisch, J. K., Benzinger, T. L., Morris, J. C., & Ances, B. M. (2020). Depression is Associated with Tau and Not Amyloid Positron Emission Tomography in Cognitively Normal Adults. Journal of Alzheimer’s Disease, 74(4), 1045-1055. https://doi.org/10.3233/JAD-191078
Banning, L. C., Ramakers, I. H., Deckers, K., Verhey, F. R., & Aalten, P. (2019). Affective symptoms and AT (N) biomarkers in mild cognitive impairment and Alzheimer’s disease: A systematic literature review. Neuroscience & Biobehavioral Reviews, 107, 346-359. https://doi.org/10.1016/j.neubiorev.2019.09.014
Baquero, M., Blasco, R., Campos-García, A., Garcés, M., Fages, E. M., & Andreu-Català, M. (2004). Descriptive study of behavioural disorders in mild cognitive impairment. Revista de Neurologia, 38(4), 323–326.
Baquero, M., & Martín, N. (2015). Depressive symptoms in neuro- degenerative diseases. World Journal of Clinical Cases, 3(8), 682-693. https://doi.org/10.12998/wjcc.v3.i8.682
Beekman, A. T., Copeland, J. R., & Prince, M. J. (1999). Review of community prevalence of depression in later life. The British Journal of Psychiatry, 174, 307-311. https://doi.org/10.1192/bjp.174.4.307
Bhalla, R. K., Butters, M. A., Becker, J. T., Houck, P. R., Snitz, B. E., Lopez, O. L., Aizentein, H. J., Raina, K. D., DeKosky, S. T., & Reynolds III,
C. F. (2009). Patterns of mild cognitive impairment after treatment of depression in the elderly. The American Journal of Geriatric Psychiatry, 17(4), 308-316. https://doi.org/10.1097/JGP.0b013e318190b8d8
Blennow, K., & Zetterberg, H. (2018). Biomarkers for Alzheimer’s disease: current status and prospects for the future. Journal of Internal Medicine, 284(6), 643-663. https://doi.org/10.1111/joim.12816
Braak, H., Zetterberg, H., Del Tredici, K., & Blennow, K. (2013). Intraneuronal tau aggregation precedes diffuse plaque deposition, but amyloid-β changes occur before increases of tau in cerebrospinal fluid. Acta Neuropathologica, 126(5), 631–641. https://doi.org/10.1007/s00401-013-1139-0
Brink, T. L., Yesavage, J. A., Lum, O., Heersema, P. H., Adey, M., & Rose, T. L. (1982). Screening tests for geriatric depression. Clinical Gerontologist, 1(1), 37-43. https://doi.org/10.1300/J018v01n01_06
Calderón, D. (2018). Epidemiología de la depresión en el adulto mayor [Epidemiology of depression in the elderly]. Revista Médica Herediana, 29(3), 182-191. https://doi.org/10.20453/rmh.v29i3.3408
Canevelli, M., Cesari, M., Lucchini, F., Valletta, M., Sabino, M., Lacorte, E., Vanacore, N., & Bruno, G. (2017). Need to recalibrate research outcomes in Alzheimer’s disease: focus on neuropsychiatric symptoms. Journal of the American Geriatrics Society, 65(9), 2071-2073.
https://doi.org/10.1111/jgs.14989
Cheng, S. T., Edwin, C. S., Lee, S. Y., Wong, J. Y., Lau, K. H., Chan, L. K., Chan, H., & Wong, M. W. (2010). The geriatric depression scale as a screening tool for depression and suicide ideation: a replication and extension. The American Journal of Geriatric Psychiatry, 18(3), 256-
https://doi.org/10.1097/JGP.0b013e3181bf9edd
Conde-Sala, J. L., Reñé-Ramírez, R., Turró-Garriga, O., Gascón-Bayarri, J., Campdelacreu-Fumadó, J., Juncadella-Puig, M., Rico-Pons, I., & Garre- Olmo, J. (2014). Severity of dementia, anosognosia, and depression in relation to the quality of life of patients with Alzheimer disease: discrepancies between patients and caregivers. The American Journal of Geriatric Psychiatry, 22(2), 138–147. https://doi.org/10.1016/j.jagp.2012.07.00
Conejero, I., Lopez-Castroman, J., Giner, L., & Baca-Garcia, E. (2016). Sociodemographic antecedent validators of suicidal behavior: a review of recent literature. Current Psychiatry Reports, 18(10), Article 94. https://doi.org/10.1007/s11920-016-0732-z
Conejero, I., Navucet, S., Keller, J., Olié, E., Courtet, P., & Gabelle, A. (2018a). A complex relationship between suicide, dementia, and amyloid: a narrative review. Frontiers in Neuroscience, 12, Article 371. https://doi.org/10.3389/fnins.2018.00371
Conejero, I., Olié, E., Courtet, P., & Calati, R. (2018b). Suicide in older adults: current perspectives. Clinical Interventions in Aging, 13, 691– 699. https://doi.org/10.2147/CIA.S130670
Dafsari, F. S., & Jessen, F. (2020). Depression—an underrecognized target for prevention of dementia in Alzheimer’s disease. Translational Psychiatry, 10(1), Article 160. https://doi.org/1-13, 10.1038/s41398-020-0839-1
Dean, B., Tsatsanis, A., Lam, L. Q., Scarr, E., & Duce, J. A. (2020). Changes in cortical protein markers of iron transport with gender, major depressive disorder and suicide. The World Journal of Biological Psychiatry, 21(2), 119–126. https://doi.org/10.1080/15622975.2018.1555377
Desseilles, M., Perroud, N., Guillaume, S., Jaussent, I., Genty, C., Malafosse, A., & Courtet, P. (2012). Is it valid to measure suicidal ideation by depression rating scales?. Journal of Affective Disorders, 136(3), 398- 404. https://doi.org/10.1016/j.jad.2011.11.013
Ekman, U., Ferreira, D., & Westman, E. (2018). The A/T/N biomarker scheme and patterns of brain atrophy assessed in mild cognitive impairment. Scientific Reports, 8(1), 1-10. https://doi.org/10.1038/s41598-018-26151-8
Fernández‐San Martín, M. I., Andrade, C., Molina, J., Muñoz, P. E., Carretero, B., Rodríguez, M., & Silva, A. (2002). Validation of the Spanish version of the geriatric depression scale (GDS) in primary care. International Journal of Geriatric Psychiatry, 17(3), 279-287. https://doi.org/10.1002/gps.588
Folstein, M. F., Folstein, S. E., & McHugh, P. R. (1975). “Mini-mental state”: a practical method for grading the cognitive state of patients for the clinician. Journal of Psychiatric Research, 12(3), 189-198.
Goñi-Sarriés, A., Blanco, M., Azcárate, L., Peinado, R., & López-Goñi, J.L. (2018). Are previous suicide attempts a risk factor for completed suicide? Psicothema, 30(1), 33-38 https://doi.org/10.7334/psicothema2016.318
Heisel, M. J., Duberstein, P. R., Lyness, J. M., & Feldman, M. D. (2010). Screening for suicide ideation among older primary care patients. The Journal of the American Board of Family Medicine, 23(2), 260-269. https://doi.org/10.3122/jabfm.2010.02.080163
Heisel, M. J., Flett, G. L., Duberstein, P. R., & Lyness, J. M. (2005). Does the geriatric depression scale (GDS) distinguish between older adults with high versus low levels of suicidal ideation? The American Journal of Geriatric Psychiatry, 13(10), 876-883. https://doi.org/10.1097/00019442-200510000-00007
Hussain, M., Kumar, P., Khan, S., Gordon, D. K., & Khan, S. (2020). Similarities Between Depression and Neurodegenerative Diseases: Pathophysiology, Challenges in Diagnosis and Treatment Options. Cureus, 12(11), Article e11613. https://doi.org/10.7759/cureus.11613
Ismail, Z., Gatchel, J., Bateman, D. R., Barcelos-Ferreira, R., Cantillon, M., Jaeger, J., Donovan, N. J., & Mortby, M. E. (2018). Affective and emotional dysregulation as pre-dementia risk markers: exploring the mild behavioral impairment symptoms of depression, anxiety, irritability,
and euphoria. International Psychogeriatrics, 30(2), 185-196. https://doi.org/10.1017/S1041610217001880
Jack, C. R., Bennett, D. A., Blennow, K., Carrillo, M. C., Feldman, H. H., Frisoni, G. B., Hampel, H., Jagust, W. J., Johnson, K. A., Knopman, D.
S., Petersen, R. C., Scheltens, P., Sperling, R. A., & Dubois, B. (2016). A/T/N: an unbiased descriptive classification scheme for Alzheimer
disease biomarkers. Neurology, 87(5), 539-547. https://doi.org/10.1212/WNL.0000000000002923
Jack, C. R., Jr, Bennett, D. A., Blennow, K., Carrillo, M. C., Dunn, B., Haeberlein, S. B., Holtzman, D. M., Jagust, W., Jessen, F., Karlawish,
J., Liu, E., Molinuevo, J. L., Montine, T., Phelps, C., Rankin, K. P., Rowe, C. C., Scheltens, P., Siemers, E., Snyder, H. M., & Sperling, R.
(2018). NIA-AA Research Framework: Toward a biological definition of Alzheimer’s disease. Alzheimer’s & Dementia, 14(4), 535–562.
https://doi.org/10.1016/j.jalz.2018.02.018
Javaherian, K., Newman, B. M., Weng, H., Hassenstab, J., Xiong, C., Coble, D., Fagan, A. M., Benzinger, T., & Morris, J. C. (2019). Examining the
complicated relationship between depressive symptoms and cognitive impairment in preclinical Alzheimer disease. Alzheimer Disease &
Associated Disorders, 33(1), 15-20. https://doi.org/10.1097/WAD.0000000000000284
Krell-Roesch, J., Vassilaki, M., Mielke, M. M., Kremers, W. K., Lowe, V. J., Vemuri, P., Machulda, M. M., Christianson, T. J., Syrjanen, J. A., Stokin,
G. B., Butler, L. M., Traber, M., Jack, C. R., Knopman, D. S., Roberts, R. O., Petersen, R. C. & Geda, Y. E. (2019). Cortical β-amyloid burden,
neuropsychiatric symptoms, and cognitive status: the Mayo Clinic Study of Aging. Translational Psychiatry, 9(1), 1-8.
https://doi.org/10.1038/s41398-019-0456-z
Lai, A. X., Kaup, A. R., Yaffe, K., & Byers, A. L. (2018). High occurrence of psychiatric disorders and suicidal behavior across dementia subtypes.
The American Journal of Geriatric Psychiatry, 26(12), 1191-1201. https://doi.org/10.1016/j.jagp.2018.08.012
Lavretsky, H., Siddarth, P., Kepe, V., Ercoli, L. M., Miller, K. J., Burggren, A. C., Bookheimer, S. Y, Huang, S. C., Barrio, J. R., & Small, G. W.
(2009). Depression and anxiety symptoms are associated with cerebral FDDNP-PET binding in middle-aged and older nondemented adults.
The American Journal of Geriatric Psychiatry, 17(6), 493-502. https://doi.org/10.1097/JGP.0b013e3181953b82
Li, N., Chen, G., Zeng, P., Pang, J., Gong, H., Han, Y., Zhang, Y., Zhang, E., Zhang, T., & Zheng, X. (2018). Prevalence and factors associated with
mild cognitive impairment among Chinese older adults with depression. Geriatrics Gerontology International, Feb;18(2), 263-268. https://doi.org/10.1111/ggi.13171
Linnemann, C., & Leyhe, T. (2015). Suicide in the elderly–risk factors and prevention. Therapeutische Umschau. Revue therapeutique, 72(10),
-636. https://doi.org/10.1024/0040-5930/a000729
Lopez, O. L., Becker, J. T., Sweet, R. A., Klunk, W., Kaufer, D. I., Saxton, J., Habeych, M., & DeKosky, S. T. (2003). Psychiatric symptoms vary with
the severity of dementia in probable Alzheimer’s disease. The Journal of Neuropsychiatry and Clinical Neurosciences, 15(3), 346-353.
Mahoney, F. I., & Barthel, D. W. (1965). Functional evaluation: the Barthel Index. Maryland State Medical Journal, 14, 61–65.
Martin, E., & Velayudhan, L. (2020). Neuropsychiatric Symptoms in Mild Cognitive Impairment: A Literature Review. Dementia and Geriatric
Cognitive Disorders, 49(2), 146–155. https://doi.org/10.1159/000507078
McKhann, G. M., Knopman, D. S., Chertkow, H., Hyman, B. T., Jack Jr, C. R., Kawas, C. H., Klunk, W. E., Koroshetz, W. J., Manly, J. J., Mayeux, R., Mohs, R. C., Morris, J. C., Rossor, M. N., Scheltens, P., Carrillo, M. C., Thies, B., Weintraub, S., & Phelps, C. H. (2011). The diagnosis of dementia due to Alzheimer’s disease: recommendations from the National Institute on Aging‐Alzheimer’s Association workgroups on diagnostic guidelines for Alzheimer’s disease. Alzheimer’s & Dementia, 7(3), 263-269. https://doi.org/10.1016/j.jalz.2011.03.005
Ng, K. P., Chiew, H., Rosa-Neto, P., Kandiah, N., Ismail, Z., & Gauthier, S. (2021). Associations of AT(N) biomarkers with neuropsychiatric symptoms in preclinical Alzheimer’s disease and cognitively unimpaired individuals. Translational Neurodegeneration, 10(1), 1-4. https://doi.org/10.1186/s40035-021-00236-3
Pérez Rodríguez, S., Marco Salvador, J. H., & García-Alandete, J. (2017). The role of hopelessness and meaning in life in a clinical sample with non- suicidal self-injury and suicide attempts. Psicothema, 29, 3, 323-328. https://doi.org/10.7334/psicothema2016.284
Petersen, R. C., Roberts, R. O., Knopman, D. S., Boeve, B. F., Geda, Y. E., Ivnik, R. J., Smith, G. E., & Jack, C. R. (2009). Mild cognitive impairment: ten years later. Archives of Neurology, 66(12), 1447-1455. https://doi.org/10.1001/archneurol.20092
Pomara, N., Bruno, D., Sarreal, A. S., Hernando, R. T., Nierenberg, J., Petkova, E., Sidtis, J. J., Wisniewski, T. M., Mehta, P. D., Pratico, D., Zetterberg, H., & Blennow, K. (2012). Lower CSF amyloid beta peptides and higher F2-isoprostanes in cognitively intact elderly individuals with major depressive disorder. American Journal of Psychiatry, 169(5), 523- 530. https://doi.org/10.1176/appi.ajp.2011.11081153
Rao, R., Dening, T., Brayne, C., & Huppert, F. A. (1997). Suicidal thinking in community residents over eighty. International Journal of Geriatric Psychiatry, 12(3), 337-343.
Sekhon, S., Patel, J., & Sapra, A. (2020). Late Onset Depression. StatPearls Publishing.
Serafini, G., Calcagno, P., Lester, D., Girardi, P., Amore, M., & Pompili, M. (2016). Suicide risk in Alzheimer’s disease: a systematic review. Current Alzheimer Research, 13(10), 1083-1099. https://doi.org/10.1002/(10.2174/1567205013666160720112608
Schoonenboom, N. S., Reesink, F. E., Verwey, N. A., Kester, M. I., Teunissen, C. E., van de Ven, P. M., Pijnenburg, Y. A., Blankenstein, M. A., Rozemuller, A. J., Scheltens, P., & van der Flier, W. M. (2012). Cerebrospinal fluid markers for differential dementia diagnosis in a large memory clinic cohort. Neurology, 78(1), 47–54. https://doi.org/10.1212/WNL.0b013e31823ed0f0
Showraki, A., Murari, G., Ismail, Z., Barfett, J. J., Fornazzari, L., Munoz, D. G., Schweizer, T. A., & Fischer, C. E. (2019). Cerebrospinal Fluid Correlates of Neuropsychiatric Symptoms in Patients with Alzheimer’s Disease/ Mild Cognitive Impairment: A Systematic Review. Journal of Alzheimer’s Disease, 71(2), 477–501. https://doi.org/10.3233/JAD-190365
Small, S. A., & Duff, K. (2008). Linking Abeta and tau in late-onset Alzheimer’s disease: a dual pathway hypothesis. Neuron, 60(4), 534– 542.
https://doi.org/10.1016/j.neuron.2008.11.007
Stepién, T., Heitzman, J., Wierzba-Bobrowicz, T., Gosek, P., Krajewski, P., Chrzczonowicz-Stepién, A., Berent, J., Jurek, T. & Bolechała, F. (2021). Neuropathological Changes in the Brains of Suicide Killers. Biomolecules, 11, Article 1674. https://doi.org/10.3390/biom11111674
Uncapher, H., & Sandberg, D. A. (1998). Using the Geriatric Depression Scale to detect suicidal ideation in inpatient older adults. Journal of Clinical Geropsychology, 4, 349-358.
Waern, M., Rubenowitz, E., & Wilhelmson, K. (2003). Predictors of suicide in the old elderly. Gerontology, 49(5), 328-334. https://doi.org/10.1159/000071715
Wenzler, S., Knochel, C., Balaban, C., Kraft, D., Kopf, J., Alves, G. S., Prvulovic, D., Carvalho, A. F., & Oertel-Knochel, V. (2017). Integrated Biomarkers for Depression in Alzheimer’s Disease: A Critical Review. Current Alzheimer Research, 14(4), 441–452. https://doi.org/10.2174/1567205013666160603011256
Wiels, W., Baeken, C., & Engelborghs, S. (2020). Depressive Symptoms in the Elderly—An Early Symptom of Dementia? A Systematic Review. Frontiers in Pharmacology, 11, Article 34. https://doi.org/10.3389/fphar.2020.00034
World Health Organization. (2020). Dementia. https://www.who.int/es/news-room/fact-sheets/detail/dementia
Yesavage, J. A., Brink, T. L., Rose, T. L., Lum, O., Huang, V., Adey, M., & Leirer, O.V. (1982). Development and validation of a geriatric depression scale. Journal of Psychiatric Research, 17, 31-49. https://doi.org/10.1016/0022-3956(82)90033-4
Yoshida, K., Hata, Y., Ichimata, S., & Nishida, N. (2019). Tau and Amyloid-β Pathology in Japanese Forensic Autopsy Series Under 40 Years of Age: Prevalence and Association with APOE Genotype and Suicide Risk. Journal of Alzheimer’s Disease, 72(2), 641-652. https://doi.org/10.3233/JAD-190196
Youn, H., Lee, S., Han, C., Kim, S. H., & Jeong, H. G. (2019). Association between brain amyloid accumulation and neuropsychological characteristics in elders with depression and mild cognitive impairment. International Journal of Geriatric Psychiatry, 34(12), 1907-1915.
https://doi.org/10.1002/gps.5209
Zhang, X. X., Tian, Y., Wang, Z. T., Ma, Y. H., Tan, L., & Yu, J. T. (2021). The Epidemiology of Alzheimer’s Disease Modifiable Risk Factors and Prevention. The Journal of Prevention of Alzheimer’s Disease, 8(3), 313-321. https://dx.doi.org/10.14283/jpad.2021.15