Cortical neuritic plaques and hippocampal neurofibrillary tangles are related to dementia severity in elderly schizophrenia patients

Rapp, Michael A.; Schnaider-Beeri, Michal; Purohit, Dushyant P.; Reichenberg, Abraham; McGurk, Susan R.; Haroutunian, Vahram; Harvey, Philip D.

doi:10.1016/j.schres.2009.10.013

« Previous Next »Schizophrenia Research
Volume 116, Issue 1 , Pages 90-96, January 2010

Cortical neuritic plaques and hippocampal neurofibrillary tangles are related to dementia severity in elderly schizophrenia patients

Michael A. Rapp
- Department of Psychiatry, Mount Sinai School of Medicine, New York, NY 10128, USA
- Department of Psychiatry, Charite Campus Mitte, 10117 Berlin, Germany
- Corresponding author. Present Address: Department of Psychiatry, Charite Campus Mitte, Chariteplatz 1, D-10117 Berlin, Germany. Tel.: +49 30 2311 2959; fax: +49 30 2311 2952.
Michal Schnaider-Beeri
- Department of Psychiatry, Mount Sinai School of Medicine, New York, NY 10128, USA
Dushyant P. Purohit
- Department of Psychiatry, Mount Sinai School of Medicine, New York, NY 10128, USA
- Department of Pathology, Mount Sinai School of Medicine, New York, NY 10128, USA
Abraham Reichenberg
- Department of Psychiatry, Mount Sinai School of Medicine, New York, NY 10128, USA
- Bronx Veterans Affairs Hospital, Bronx, NY 10468, USA
Susan R. McGurk
- Department of Psychiatry, Mount Sinai School of Medicine, New York, NY 10128, USA
Vahram Haroutunian
- Department of Psychiatry, Mount Sinai School of Medicine, New York, NY 10128, USA
- Institute of Psychiatry, London SE5 8AF, UK
Philip D. Harvey
- Department of Psychiatry, Mount Sinai School of Medicine, New York, NY 10128, USA
- Department of Psychiatry, Emory University, Atlanta, GA 30322, USA

Received 10 May 2009; received in revised form 12 October 2009; accepted 17 October 2009. published online 09 November 2009.

Abstract

Cognitive decline has been described in elderly patients with schizophrenia, but the underlying pathology remains unknown. Some studies report increases in plaques and neurofibrillary tangles, but there is no evidence for an increased risk for Alzheimer's disease (AD) in elderly schizophrenics. Models of a decreased cerebral reserve suggest that increases in AD-related neuropathology below the threshold for a neuropathological diagnosis could be related to dementia severity in elderly schizophrenia patients. We tested this hypothesis in 110 autopsy specimens of schizophrenia patients, without a neuropathological diagnosis of AD or other neurodegenerative disorders. Furthermore, we assessed the effects of apolipoprotein E (ApoE) status, a known genetic risk factor for AD. Measures of density of neuritic plaques were obtained in five cortical regions, and the degree of hippocampal neurofibrillary tangles was rated. Dementia severity was measured prior to postmortem using the Clinical Dementia Rating (CDR) scale. multivariate analyses of variance were conducted with the factors dementia severity, by ApoE4 carrier status. Hippocampal neurofibrillary tangles correlated with increased dementia severity (p<.05). Neuritic plaque density increased with greater dementia severity (p<.005), and ApoE4 carrier status (p<.005), and these differences were magnified by the ApoE4 carrier status (p<.01). Even below the threshold for a neuropathological diagnosis of AD, neuritic plaques and hippocampal neurofibrillary tangles are associated with dementia severity in schizophrenia patients, even more so in the presence of genetic risk factors, suggesting that a decreased cerebral reserve in elderly schizophrenics may increase susceptibility for dementia.