title: Cortical neuritic plaques and hippocampal neurofibrillary tangles are related to dementia severity in elderly schizophrenia patients.
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.
authors.affiliation: Department of Psychiatry, Mount Sinai School of Medicine, New York, NY 10128, USA. michael.rapp@charite.de
authors.forename: Michael A
authors.initials: MA
authors.lastname: Rapp
authors.forename: Michal
authors.initials: M
authors.lastname: Schnaider-Beeri
authors.forename: Dushyant P
authors.initials: DP
authors.lastname: Purohit
authors.forename: Abraham
authors.initials: A
authors.lastname: Reichenberg
authors.forename: Susan R
authors.initials: SR
authors.lastname: McGurk
authors.forename: Vahram
authors.initials: V
authors.lastname: Haroutunian
authors.forename: Philip D
authors.initials: PD
authors.lastname: Harvey
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D053327:Apolipoprotein E4 / Q000235:genetics; D002540:Cerebral Cortex / Q000473:pathology*; D016009:Chi-Square Distribution; D003072:Cognition Disorders / Q000209:etiology / Q000473:pathology; D003704:Dementia / Q000209:etiology / Q000235:genetics / Q000473:pathology*; D005260:Female; D015577:Geriatric Assessment; D006624:Hippocampus / Q000473:pathology*; D006801:Humans; D008297:Male; D016874:Neurofibrillary Tangles / Q000235:genetics / Q000473:pathology*; D009483:Neuropsychological Tests; D058225:Plaque, Amyloid / Q000473:pathology*; D011180:Postmortem Changes; D011569:Psychiatric Status Rating Scales; D012559:Schizophrenia / Q000150:complications / Q000235:genetics / Q000473:pathology*; D012720:Severity of Illness Index
chemical_list: D053327:Apolipoprotein E4