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Clinicopathological investigation of the background of cognitive decline in elderly schizophrenia

Published online by Cambridge University Press:  04 November 2020

Ayako Miwa
Affiliation:
Moriyama General Mental Hospital, Aichi, Japan
Mitsuaki Hirano*
Affiliation:
Department of Psychiatry, Nagoya University Graduate School of Medicine, Aichi, Japan
Youta Torii
Affiliation:
Moriyama General Mental Hospital, Aichi, Japan Department of Psychiatry, Nagoya University Graduate School of Medicine, Aichi, Japan
Hirotaka Sekiguchi
Affiliation:
Okehazama Hospital Fujita Mental Care Center & the Neuroscience Research Center, Aichi, Japan
Chikako Habuchi
Affiliation:
Aichi Psychiatric Medical Center, Aichi, Japan
Hiroshige Fujishiro
Affiliation:
Department of Psychiatry, Nagoya University Graduate School of Medicine, Aichi, Japan Kawasaki Memorial Hospital, Kanagawa, Japan
Mari Yoshida
Affiliation:
Department of Neuropathology, Institute for Medical Science of Aging, Aichi Medical University, Aichi, Japan
Kiyoshi Iwai
Affiliation:
Moriyama General Mental Hospital, Aichi, Japan
Kunihiro Kawashima
Affiliation:
Moriyama General Mental Hospital, Aichi, Japan
Shuji Iritani
Affiliation:
Moriyama General Mental Hospital, Aichi, Japan Department of Psychiatry, Nagoya University Graduate School of Medicine, Aichi, Japan
*
Author for correspondence: Mitsuaki Hirano, Email: mthiranomthirano@yahoo.co.jp

Abstract

Objective:

We have often observed dementia symptoms or severe neurocognitive decline in the long-term course of schizophrenia. While there are epidemiological reports that patients with schizophrenia are at an increased risk of developing dementia, there are also neuropathological reports that the prevalence of Alzheimer’s disease (AD) in schizophrenia is similar to that in normal controls. It is difficult to distinguish, based solely on the clinical symptoms, whether the remarkable dementia symptoms and cognitive decline seen in elderly schizophrenia are due to the course of the disease itself or a concomitant neurocognitive disease. Neuropathological observation is needed for discrimination.

Methods:

We conducted a neuropathological search on three cases of schizophrenia that developed cognitive decline or dementia symptoms after a long illness course of schizophrenia. The clinical symptoms of total disease course were confirmed retrospectively in the medical record. We have evaluated neuropathological diagnosis based on not only Hematoxylin–Eosin and Klüver–Barrera staining specimens but also immunohistochemical stained specimens including tau, β-amyloid, pTDP-43 and α-synuclein protein throughout clinicopathological conference with multiple neuropathologists and psychiatrists.

Results:

The three cases showed no significant pathological findings or preclinical degenerative findings, and poor findings consistent with symptoms of dementia were noted.

Conclusion:

Although the biological background of dementia symptoms in elderly schizophrenic patients is still unclear, regarding the brain capacity/cognitive reserve ability, preclinical neurodegeneration changes in combination with certain brain vulnerabilities due to schizophrenia itself are thought to induce dementia syndrome and severe cognitive decline.

Type
Original Article
Copyright
© Scandinavian College of Neuropsychopharmacology 2020

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References

Arnold, SE and Trojanowski, JQ (1996a) Cognitive impairment in elderly schizophrenia: a dementia (still) lacking distinctive histopathology. Schizophrenia Bulletin 22(1), 59.CrossRefGoogle ScholarPubMed
Arnold, SE and Trojanowski, JQ (1996b) Recent advances in defining the neuropathology of schizophrenia. Acta Neuropathologica 92(3), 217231.CrossRefGoogle ScholarPubMed
American Psychiatric Association (APA) (ed) (2013) Diagnostic and Statistical Manual of Mental Disorders (DSM-5®).CrossRefGoogle Scholar
Braak, H, Alafuzoff, I, Arzberger, T, Kretzschmar, H and Del Tredici, K (2006) Staging of Alzheimer disease-associated neurofibrillary pathology using paraffin sections and immunocytochemistry. Acta Neuropathologica 112(4), 389404.CrossRefGoogle ScholarPubMed
Braak, H and Braak, E (1991) Neuropathological stageing of Alzheimer-related changes. Acta Neuropathologica 82(4), 239259.CrossRefGoogle ScholarPubMed
Braak, H, Del Tredici, K, Rub, U, de Vos, RA, Jansen Steur, EN and Braak, E (2003) Staging of brain pathology related to sporadic Parkinson’s disease. Neurobiology of Aging 24(2), 197211.CrossRefGoogle ScholarPubMed
Cai, L and Huang, J (2018) Schizophrenia and risk of dementia: a meta-analysis study. Neuropsychiatric Disease and Treatment 14, 20472055.CrossRefGoogle ScholarPubMed
Der, G, Gupta, S and Murray, RM (1990) Is schizophrenia disappearing? Lancet 335(8688), 513516.CrossRefGoogle Scholar
Eyler, LT and Jeste, DV (2018) Aging of the body and the brain in schizophrenia. Schizophrenia Research 196, 13.CrossRefGoogle Scholar
Giusti-Rodriguez, P and Sullivan, PF (2013) The genomics of schizophrenia: update and implications. Journal of Clinical Investigation 123(11), 45574563.CrossRefGoogle ScholarPubMed
Guo, JY, Huhtaniska, S, Miettunen, J, Jaaskelainen, E, Kiviniemi, V, Nikkinen, J, Moilanen, J, Haapea, M, Maki, P, Jones, PB, Veijola, J, Isohanni, M and Murray, GK (2015) Longitudinal regional brain volume loss in schizophrenia: Relationship to antipsychotic medication and change in social function. Schizophrenia Research 168(1–2), 297304.CrossRefGoogle ScholarPubMed
Hoenig, J (1983) The concept of Schizophrenia. Kraepelin-Bleuler-Schneider. British Journal of Psychiatry 142, 547556.CrossRefGoogle ScholarPubMed
Jeong, JW, Kim, KW, Lee, DY, Lee, SB, Park, JH, Choi, EA, Choe, JY, Do, YJ, Ryang, JS, Roh, HA, Park, YS, Choi, Y, Woo, JI (2007) A normative study of the Revised Hasegawa Dementia Scale: comparison of demographic influences between the Revised Hasegawa Dementia Scale and the Mini-mental Status Examination. Dementia and Geriatric Cognitive Disorders 24(4), 288293.CrossRefGoogle ScholarPubMed
Kahn, RS and Keefe, RS (2013) Schizophrenia is a cognitive illness: time for a change in focus. JAMA Psychiatry 70(10), 11071112.CrossRefGoogle ScholarPubMed
Kendler, KS and Engstrom, EJ (2018) Criticisms of Kraepelin’s Psychiatric Nosology: 1896–1927. The American Journal of Psychiatry 175(4), 316326.CrossRefGoogle ScholarPubMed
Kishi, T, Matsunaga, S, Oya, K, Nomura, I, Ikuta, T and Iwata, N (2017) Memantine for Alzheimer’s Disease: An Updated Systematic Review and Meta-analysis. Journal of Alzheimerʼs Disease 60(2), 401425.CrossRefGoogle ScholarPubMed
Kon, T, Tomiyama, M and Wakabayashi, K (2020) Neuropathology of Lewy body disease: clinicopathological crosstalk between typical and atypical cases. Neuropathology 40(1), 3039.CrossRefGoogle ScholarPubMed
Ladea, M and Prelipceanu, D (2009) Markers of vulnerability in schizophrenia. Journal of Medicine and Life 2(2), 155164.Google Scholar
Lang, FU, Kosters, M, Lang, S, Becker, T and Jager, M (2013) Psychopathological long-term outcome of schizophrenia -- a review. Acta Psychiatrica Scandinavica 127(3), 173182.CrossRefGoogle ScholarPubMed
Li, XM and Xu, H (2007) Evidence for neuroprotective effects of antipsychotic drugs: implications for the pathophysiology and treatment of schizophrenia. International Review of Neurobiology 77, 107142.CrossRefGoogle ScholarPubMed
Lieberman, J, Chakos, M, Wu, H, Alvir, J, Hoffman, E, Robinson, D and Bilder, R (2001) Longitudinal study of brain morphology in first episode schizophrenia. Biological Psychiatry 49(6), 487499.CrossRefGoogle ScholarPubMed
McKeith, IG, Dickson, DW, Lowe, J, Emre, M, O’Brien, JT, Feldman, H, Cummings, J, Duda, JE, Lippa, C, Perry, EK, Aarsland, D, Arai, H, Ballard, CG, Boeve, B, Burn, DJ, Costa, D, Del Ser, T, Dubois, B, Galasko, D, Gauthier, S, Goetz, CG, Gomez-Tortosa, E, Halliday, G, Hansen, LA, Hardy, J, Iwatsubo, T, Kalaria, RN, Kaufer, D, Kenny, RA, Korczyn, A, Kosaka, K, Lee, VM, Lees, A, Litvan, I, Londos, E, Lopez, OL, Minoshima, S, Mizuno, Y, Molina, JA, Mukaetova-Ladinska, EB, Pasquier, F, Perry, RH, Schulz, JB, Trojanowski, JQ, Yamada, M and Consortium on DLB (2005) Diagnosis and management of dementia with Lewy bodies: third report of the DLB Consortium. Neurology 65(12), 18631872.CrossRefGoogle ScholarPubMed
Mirra, SS, Heyman, A, McKeel, D, Sumi, SM, Crain, BJ, Brownlee, LM, Vogel, FS, Hughes, JP, van Belle, G and Berg, L (1991) The Consortium to Establish a Registry for Alzheimer’s Disease (CERAD). Part II. Standardization of the neuropathologic assessment of Alzheimer’s disease. Neurology 41(4), 479486.CrossRefGoogle Scholar
Murray, RM, Bhavsar, V, Tripoli, G and Howes, O (2017) 30 years on: how the neurodevelopmental hypothesis of schizophrenia morphed into the developmental risk factor model of psychosis. Schizophrenia Bulletin 43(6), 11901196.CrossRefGoogle Scholar
Niizato, K, Arai, T, Kuroki, N, Kase, K, Iritani, S and Ikeda, K (1998) Autopsy study of Alzheimer’s disease brain pathology in schizophrenia. Schizophrenia Research 31(2–3), 177184.CrossRefGoogle Scholar
Perez-Neri, I, Ramirez-Bermudez, J, Montes, S and Rios, C (2006) Possible mechanisms of neurodegeneration in schizophrenia. Neurochemical Research 31(10), 12791294.CrossRefGoogle Scholar
Pino, O, Guilera, G, Gomez-Benito, J, Najas-Garcia, A, Rufian, S and Rojo, E (2014) Neurodevelopment or neurodegeneration: review of theories of schizophrenia. Actas Españolas de Psiquiatría 42(4), 185195.Google ScholarPubMed
Plum, F (1972) Prospects for research on schizophrenia. 3. Neurophysiology. Neuropathological findings. Neurosciences Research Program Bulletin 10(4), 384388.Google ScholarPubMed
Rund, BR (2018) The research evidence for schizophrenia as a neurodevelopmental disorder. Scandinavian Journal of Psychology 59(1), 4958.CrossRefGoogle ScholarPubMed
Saito, Y, Ruberu, NN, Sawabe, M, Arai, T, Tanaka, N, Kakuta, Y, Yamanouchi, H and Murayama, S (2004) Staging of argyrophilic grains: an age-associated tauopathy. Journal of Neuropathology & Experimental Neurology 63(9), 911918.CrossRefGoogle Scholar
Sarter, M (1994) Neuronal mechanisms of the attentional dysfunctions in senile dementia and schizophrenia: two sides of the same coin? Psychopharmacology (Berl) 114(4), 539550.CrossRefGoogle ScholarPubMed
Sarter, M, Lustig, C and Taylor, SF (2012) Cholinergic contributions to the cognitive symptoms of schizophrenia and the viability of cholinergic treatments. Neuropharmacology 62(3), 15441553.CrossRefGoogle ScholarPubMed
Schmitt, A and Falkai, P (2014) The neuropathology of schizophrenia: new insights from postmortem studies. European Archives of Psychiatry and Clinical Neuroscience 264(4), 269270.CrossRefGoogle ScholarPubMed
Thal, DR, Rub, U, Orantes, M and Braak, H (2002) Phases of A beta-deposition in the human brain and its relevance for the development of AD. Neurology 58(12), 17911800.CrossRefGoogle ScholarPubMed
Togo, T, Isojima, D, Akstu, H, Suzuki, K, Uchikado, H, Katsuze, O, Iseki, E, Kosaka, K and Hirayasu, Y (2005) Clinical features of argyrophilic grain disease: a retrospective survey of cases with neuropsychiatric symptoms. The American Journal of Geriatric Psychiatry 13(12), 10831091.CrossRefGoogle ScholarPubMed
Van Haren, NE, Cahn, W, Hulshoff Pol, HE and Kahn, RS (2013) Confounders of excessive brain volume loss in schizophrenia. Neuroscience & Biobehavioral Reviews 37(10 Pt 1), 24182423.CrossRefGoogle Scholar
van Os, J and Kapur, S (2009) Schizophrenia. Lancet 374(9690), 635645.CrossRefGoogle ScholarPubMed
Veijola, J, Guo, JY, Moilanen, JS, Jaaskelainen, E, Miettunen, J, Kyllonen, M, Haapea, M, Huhtaniska, S, Alaraisanen, A, Maki, P, Kiviniemi, V, Nikkinen, J, Starck, T, Remes, JJ, Tanskanen, P, Tervonen, O, Wink, AM, Kehagia, A, Suckling, J, Kobayashi, H, Barnett, JH, Barnes, A, Koponen, HJ, Jones, PB, Isohanni, M and Murray, GK (2014) Longitudinal changes in total brain volume in schizophrenia: relation to symptom severity, cognition and antipsychotic medication. PLoS One 9(7), e101689.CrossRefGoogle ScholarPubMed
Vita, A, Deste, G, De Peri, L, Barlati, S, Poli, R, Cesana, BM and Sacchetti, E (2013) Predictors of cognitive and functional improvement and normalization after cognitive remediation in patients with schizophrenia. Schizophrenia Research 150(1), 5157.CrossRefGoogle ScholarPubMed