THE RELATIONSHIP BETWEEN SCHIZOPHRENIA AND ALZHEIMER'S DISEASE - AN ATTEMPT TO A HOLISTIC VIEW OF NEURODEGENERATIVE DISORDERS
DOI:
https://doi.org/10.31435/ijitss.3(51).2026.5858Keywords:
Schizophrenia, Alzheimer's Disease, Dementia, Therapeutic Strategies, BiomarkersAbstract
Schizophrenia and Alzheimer's disease are serious neurological disorders that, despite their different clinical pictures, show significant connections at the neuroanatomical, genetic, and functional levels. Research suggests that patients with schizophrenia have an increased risk of developing dementia, including Alzheimer's disease. Neuroimaging analyses indicate similarities in white matter damage, reduction in the volume of the hippocampus and prefrontal cortex, suggesting common neurodegenerative mechanisms that lead to cognitive impairment and behavioral changes. Genetic studies show a partial overlap in the polygenic risk of schizophrenia and Alzheimer's disease, especially in the genes related to neurotransmission, neuroinflammation, and synaptic function. Furthermore, the occurrence of psychotic symptoms in Alzheimer's disease may have different mechanisms than in schizophrenia, which significantly affects the effectiveness of therapy. Second-generation drugs, such as risperidone or aripiprazole, exhibit varying effectiveness depending on the neuropathological basis of psychosis, which underscores the need for individualized therapy and the search for new treatment strategies. New research directions focus on identifying neurodegenerative biomarkers and innovative therapeutic methods. There is particular hope for anti-PD-1 immunotherapy, which can modulate the inflammatory response and slow the progression of Alzheimer's disease. Additionally, the development of liquid biomarkers and advanced neuroimaging studies may enable earlier detection of pathological changes, which will allow for more effective therapeutic intervention.
References
Gałecki, P., & Szulc, A. (2023). Psychiatria tom 1–2. Edra Urban & Partner.
Kraepelin, E. (1919). Dementia praecox and paraphrenia (R. M. Barclay, Trans.). E. & S. Livingstone. (Original work published 1896)
Cai, L., & Huang, J. (2018). Schizophrenia and risk of dementia: A meta-analysis study. Neuropsychiatric Disease and Treatment, 2047–2055. https://doi.org/10.2147/NDT.S172933
Fischer, C. E., & Agüera-Ortiz, L. (2018). Psychosis and dementia: Risk factor, prodrome, or cause? International Psychogeriatrics, 30(2), 209–219. https://doi.org/10.1017/S1041610217000874
Ribe, A. R., Laursen, T. M., Charles, M., et al. (2015). Long-term risk of dementia in persons with schizophrenia: A Danish population-based cohort study. JAMA Psychiatry, 72(11), 1095–1101. https://doi.org/10.1001/jamapsychiatry.2015.1546
Husa, A. P., Moilanen, J., Murray, G. K., Marttila, R., Haapea, M., Rannikko, I., Barnett, J. H., Jones, P. B., Isohanni, M., Remes, A. M., Koponen, H., Miettunen, J., & Jääskeläinen, E. (2017). Lifetime antipsychotic medication and cognitive performance in schizophrenia at age 43 years in a general population birth cohort. Psychiatry Res., 247, 130–138. https://doi.org/10.1016/j.psychres.2016.10.085
Kochunov, P., Zavaliangos-Petropulu, A., Jahanshad, N., Thompson, P. M., Ryan, M. C., Chiappelli, J., Chen, S., Du, X., Hatch, K., Adhikari, B., Sampath, H., Hare, S., Kvarta, M., Goldwaser, E., Yang, F., Olvera, R. L., Fox, P. T., Curran, J. E., Blangero, J., … Hong, L. E. (2021). A white matter connection of schizophrenia and Alzheimer’s disease. Schizophrenia Bulletin, 47(1), 197–206.
Manca, R., Pardiñas, A. F., Venneri, A., & Alzheimer’s Disease Neuroimaging Initiative. (2023). The neural signatures of psychoses in Alzheimer's disease: A neuroimaging genetics approach. Eur Arch Psychiatry Clin Neurosci., 273(1), 253–267.
Serra, L., Perri, R., Cercignani, M., Spanò, B., Fadda, L., Marra, C., Carlesimo, G. A., Caltagirone, C., & Bozzali, M. (2010). Are the behavioral symptoms of Alzheimer’s disease directly associated with neurodegeneration? J Alzheimers Dis, 21, 627–639.
Chen, J., Bacanu, S. A., Yu, H., et al. (2016). Genetic relationship between schizophrenia and nicotine dependence. Sci Rep, 6, 25671.
DeMichele-Sweet, M. A. A., Weamer, E. A., Klei, L., Vrana, D. T., Hollingshead, D. J., Seltman, H. J., Sims, R., Foroud, T., Hernandez, I., Moreno-Grau, S., Tárraga, L., Boada, M., Ruiz, A., Williams, J., Mayeux, R., Lopez, O. L., Sibille, E. L., Kamboh, M. I., Devlin, B., & Sweet, R. A. (2018). Genetic risk for schizophrenia and psychosis in Alzheimer disease. Mol Psychiatry, 23(4), 963–972.
Fan, P., Kofler, J., Ding, Y., Marks, M., Sweet, R. A., & Wang, L. (2022). Efficacy difference of antipsychotics in Alzheimer's disease and schizophrenia: Explained with network efficiency and pathway analysis methods. Brief Bioinform., 23(6), bbac394.
Haque, R., Watson, C. M., Liu, J., Carter, E. K., Duong, D. M., Lah, J. J., Wingo, A. P., Roberts, B. R., Johnson, E. C. B., Saykin, A. J., Shaw, L. M., Seyfried, N. T., Wingo, T. S., & Levey, A. I. (2023). A protein panel in cerebrospinal fluid for diagnostic and predictive assessment of Alzheimer's disease. Sci Transl Med., 15(712), eadg4122.
Ismail, Z., Creese, B., Aarsland, D., et al. (2022). Psychosis in Alzheimer disease — mechanisms, genetics and therapeutic opportunities. Nat Rev Neurol, 18, 131–144.
Schwartz, M., Arad, M., & Ben-Yehuda, H. (2019). Potential immunotherapy for Alzheimer disease and age-related dementia. Dialogues in Clinical Neuroscience, 21(1), 21–25.
Baruch, K., Deczkowska, A., Rosenzweig, N., et al. (2016). PD-1 immune checkpoint blockade reduces pathology and improves memory in mouse models of Alzheimer's disease. Nat Med, 22, 135–137.
Ghareghani, M., & Rivest, S. (2023). The synergistic potential of combining PD-1/PD-L1 immune checkpoint inhibitors with NOD2 agonists in Alzheimer’s disease treatment. Int. J. Mol. Sci., 24, 10905.
Grabert, K., Michoel, T., Karavolos, M. H., Clohisey, S., Baillie, J. K., Stevens, M. P., Freeman, T. C., Summers, K. M., & McColl, B. W. (2016). Microglial brain region−dependent diversity and selective regional sensitivities to aging. Nat. Neurosci., 19, 504–516.
Mukherjee, A., Biswas, S., & Roy, I. (2024). Immunotherapy: An emerging treatment option for neurodegenerative diseases. Drug Discovery Today, 29(5), 103974.
Cao, J., Hou, J., Ping, J., et al. (2018). Advances in developing novel therapeutic strategies for Alzheimer’s disease. Mol Neurodegeneration, 13, 64.
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Copyright (c) 2026 Mateusz Korowacki, Amadea Wrzesińska, Iga Rusin, Krystian Mączka, Daniel Grobecki, Karol Kazimierczak, Michał Przybylski, Filip Kruczek, Jakub Dyczko, Bartosz Świrad
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