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A Postmortem Neuropathologic Study of 100 Cases

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A Postmortem Neuropathologic Study of 100 Cases ORIGINAL ARTICLE Alzheimer Disease and Related Neurodegenerative Diseases in Elderly Patients With Schizophrenia A Postmortem Neuropathologic Study of 100 Cases Dushyant P. Purohit, MD; Daniel P. Perl, MD; Vahram Haroutunian, PhD; Peter Powchik, MD; Michael Davidson, MD; Kenneth L. Davis, MD Background: Clinical studies suggest that severe cognitive im- nile plaques or neurofibrillary tangles was not different pairment is common among elderly patients with schizophrenia in the group with schizophrenia compared with the age- who reside in long-stay psychiatric institutions; however, previ- matched controls or the group with nonschizophrenic ous autopsy-based neuropathologic investigations have provided psychiatric disorders. The higher Clinical Dementia Rat- conflicting results about the occurrence of Alzheimer disease (AD) ing Scale scores lacked correlation with neuropatho- in elderly patients with schizophrenia. We report the results of a logic evidence of dementing disorders. In the 87 cases comprehensive neuropathologic study performed to identify AD lacking a neuropathologic diagnosis of AD or other de- and other dementing neurodegenerative diseases in elderly pa- menting disorders, the mean (±SD) Clinical Dementia Rat- tients with schizophrenia. ing Scale score was 2.21 (±1.14), with 43 of the cases scor- ing 3 or higher (indicating severe, profound, or terminal Methods: A neuropathologic examination was per- cognitive impairment). formed on 100 consecutive autopsy brain specimens of patients aged 52 to 101 years (mean, 76.5 years). A cog- Conclusions: This study provides evidence that el- nitive assessment of these cases was also done by em- derly patients with schizophrenia are not inordinately ploying the Clinical Dementia Rating Scale. For com- prone to the development of AD or to increased senile parison, we included 47 patients with nonschizophrenic plaques or neurofibrillary tangle formation in the brain. psychiatric disorders from the same psychiatric hospital Other dementing neurodegenerative disorders are also and 50 age-matched control subjects. uncommon. The cognitive impairment in elderly pa- tients with schizophrenia must, therefore, be related to Results: Although 72% of the patients with schizophre- some alternative mechanisms. nia showed cognitive impairment, AD was diagnosed in only 9% of the patients and other dementing diseases were Arch Gen Psychiatry. 1998;55:205-211 diagnosed in only 4% of the patients. The degree of se- EVERAL CLINICAL studies have the frequency of AD or AD-related lesions. reported that relatively severe These varying findings may have resulted cognitive impairment is seen from several limiting factors, including a in a high proportion of el- small sample size examined, a limited neu- derly patients with schizo- ropathologic evaluation, absence of a prop- phrenia who reside in long-stay psychiat- erly age-matched control group, or reliance S 1-6 ric institutions. It has also been suggested on archival postmortem reports. that the cognitive impairment seen in these A further shortcoming of these studies patients is progressive6 and is not attribut- was a lack of correlative clinicopathologic as- able to a lack of cooperation, attention, or sessments comparing the cognitive impair- motivation or to exposure to neuroleptic ment during life with the extent of neuro- medications.6-9 These observations raise pathologiclesionsinthebrainspecimens.We questions about whether cognitive impair- previously reported the results of a prelimi- ment represents a late outcome of schizo- nary clinicopathologic study based on 13 phrenia itself or whether elderly patients cases13 and addressed this and some previ- From the Neuropathology with schizophrenia are more susceptible ously mentioned shortcomings. The results Division, Departments of than the general population to the devel- Pathology (Drs Purohit and Perl) and Psychiatry opment of Alzheimer disease (AD) or other (Drs Haroutunian, Powchik, recognized dementing neurodegenerative diseases.Postmortemneuropathologicstud- This article is also available on our Davidson, and Davis), Mount Web site: www.ama-assn.org/psych. Sinai Medical Center, ies in elderly patients with schizophrenia New York, NY. have provided conflicting findings9-13 about ARCH GEN PSYCHIATRY/ VOL 55, MAR 1998 205 ©1998 American Medical Association. All rights reserved. Downloaded From: https://jamanetwork.com/ on 09/26/2021 PARTICIPANTS AND METHODS For the comparison of the neuropathologic lesions, 47 consecutive autopsy cases (of patients aged 53-106 years; mean [±SD], 76.9±11.4 years) with clinical diagnoses of non- CASE SELECTION schizophrenic psychiatric disorders were obtained from the same hospital. We also selected, from the general hospital Institutional review board approval was granted for this study autopsy service (at Mount Sinai Hospital), 50 control cases by Mount Sinai Medical Center, New York, NY, and Pilgrim lacking a clinical history of dementia or any psychiatric dis- Psychiatric Center, Brentwood, NY. One hundred cases of orders. These cases were age matched to the schizophre- chronic schizophrenia (of patients aged 52-101 years; mean nia series (range, 52-99 years; mean [±SD], 76.5±11.0 years). [±SD], 78.5±10.5 years) made up a consecutive autopsy se- ries at the Pilgrim Psychiatric Center, a large, state-run, long- NEUROPATHOLOGIC METHODS term care psychiatric hospital situated in metropolitan New York. Selection bias in this study was avoided by recruiting The brain specimens were received in 10% buffered for- the subjects irrespective of their cognitive status or severity malin fixative and usually consisted of the entire right half of psychiatric illness, during the clinical assessment and for of the brain. All specimens were examined to identify and the autopsy. The age of the subjects at autopsy (.50 years) document the extent and distribution of neuropathologic was the only selection criteria. Sixty-nine cases were clini- lesions of AD and related neurodegenerative diseases us- cally assessed by a research team of clinicians (led by P.P. and ing a protocol standardized for the Alzheimer’s Disease Re- M.D.) within 18 months prior to death. The remaining 31 search Center at the Mount Sinai/Bronx Veterans Admin- cases were assessed by the same team from retrospective medi- istration Medical Centers. This protocol was adopted from cal record reviews. All cases included in the study met the the neuropathologic procedures devised by the Consor- DSM-III-R criteria for a clinical diagnosis of schizophrenia. tium to Establish a Registry for Alzheimer’s Disease.16 In addition, the research team assessed the cognitive status According to this protocol, tissue blocks were obtained of the cases by using the CDR,15 based on multiple informa- for paraffin sections from 5 areas of the neocortex and from tion sources, including the patient examination (available for the rostral and caudal hippocampus, the basal nucleus of Mey- 69 cases), interviews with the caregivers, and medical re- nert, the amygdala, the mesencephalon, the pons, the medulla, cord reviews. Harvey et al,8 in a study on methods of cogni- and the cerebellum (see Purohit et al13 for full details). The par- tive assessment in elderly patients with schizophrenia, found affin sections were stained with hematoxylin and eosin, thio- that standard cognitive rating scales provided reliable rat- flavin S, and modified Bielschowsky stains. Additionally, we ings and also that cognitive assessments achieved a higher performed immunohistological testing for ubiquitin to identify degree of reliability when multiple information sources were Lewy body formation in the substantia nigra and neocortex. employed. Accordingly, multiple information sources were An assessment of the presence and degree of AD- employed in the CDR assessments. The CDR scores were related changes was performed blind to clinical informa- expressed numerically with increasing grades of cognitive tion by 2 experienced neuropathologists (D.P.P. and D.P.P.). impairment as follows: 0, cognitively intact; 0.5, minimal This assessment (employing a 4-point scale: absent, sparse, impairment; 1, mild impairment; 2, moderate impairment; moderate, and severe) included estimates for the density 3, severe impairment; 4, profound impairment; and 5, ter- of senile plaques (SPs) containing neuritic change and amy- minal state of cognitive impairment. loid cores and neurofibrillary tangles (NFTs) at a magni- of that study indicated that AD-related changes were no more 3 (severe cognitive impairment) or higher and 72 of the prevalent in elderly patients with schizophrenia than in an patients scoring 2 (moderate cognitive impairment) or age-matched elderly population without schizophrenia, de- higher. The postmortem neuropathologic examination spite the occurrence of severe cognitive impairment in the findings revealed that only 9 of the 100 patients met the group with a psychiatric disorder. We report the compre- neuropathologic criteria for a diagnosis of AD. Other, more hensive neuropathologic findings of 100 consecutive autop- uncommon, dementing neurodegenerative diseases in- sies performed on elderly patients with chronic schizophre- cluded 2 cases of Parkinson disease and 1 case of multi- nia who resided in a large, long-stay psychiatric institution. infarct dementia. There was also 1 case of multiple scle- The clinical diagnosis of schizophrenia was confirmed by rosis. Diffuse cortical Lewy body disease was found in 1 a research team of clinicians
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