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, ß-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.
Subject(s)
Brain/pathology , Cognitive Dysfunction/psychology , Dementia/psychology , Neuropathology/methods , Schizophrenia/diagnosis , Aged , Aged, 80 and over , Alzheimer Disease/diagnosis , Alzheimer Disease/etiology , Alzheimer Disease/psychology , Amyloid beta-Peptides/metabolism , Autopsy/methods , Brain/diagnostic imaging , Brain/metabolism , Cognitive Dysfunction/diagnosis , Cognitive Dysfunction/etiology , DNA-Binding Proteins/metabolism , Dementia/etiology , Dementia/pathology , Diagnosis , Female , Humans , Immunohistochemistry/methods , Lewy Bodies/pathology , Male , Middle Aged , Prevalence , Retrospective Studies , Schizophrenia/complications , Schizophrenia/epidemiology , Schizophrenic Psychology , Tomography, X-Ray Computed/methods , alpha-Synuclein/metabolism , tau Proteins/metabolismABSTRACT
In the present study the occurrence and distribution of glial fibrillary tangles (GFT) and their related structures in diffuse neurofibrillary tangles with calcification (DNTC) were investigated using Gallyas-Braak (GB) stain. Six cases neuropathologically diagnosed as DNTC were studied (two males and four females). The age at death ranged from 56 to 73 years, with an average of 63.5+/-7.5 years. GFT were classified morphologically, and their immunoreactivites for tau and ubiquitin were examined. Glial cells with GFT were identified with astrocytes and oligodendrocytes by immunostain for glial fibrillary acidic protein and transferrin, respectively. A small number of coiled bodies detected within the oligodendrocytes in the white matter of the cerebrum were positive for tau and ubiquitin. Cell clusters of thorn-shaped astrocytes were detected in the subcortical and subpial regions where gliosis occurred. Thorn-shaped astrocytes were positive for tau, but negative for ubiquitin. A small number of tuft-shaped astrocytes detected prominently in the temporal cortex and amygdala with numerous neurofibrillary tangles were positive for tau and ubiquitin. All three types of GFT were detected, especially in the temporal and limbic lobes, which were the most severely affected sites in DNTC. Moreover, various-shaped neurofibrillary tangles, aggregated rods and some argyrophilic threads were differentiated from GFT. They were positive for GB, but not detected within the glial cells.
