The belief that Alzheimer's disease is commoner in schizophrenia (independent of any cognitive impairment) originated in the 1930s. It received some recent support from three uncontrolled, retrospective studies, and tangentially from data suggesting that antipsychotic drugs promote neurofibrillary tangles. However, a meta-analysis shows that Alzheimer's disease is not more common, and may even be rarer, in schizophrenia. (29> This applies even in elderly schizophrenic patients with prospectively assessed severe dementia, who show no evidence of any other neurodegenerative disorder.(30) Nor is there good evidence that antipsychotic drugs cause Alzheimer-type changes. How, therefore, is the cognitive impairment of schizophrenia explained? One possibility is that it is a more severe manifestation of whatever substrate underlies schizophrenia. Or, it may be that the brain in schizophrenia is more vulnerable to cognitive impairment in response to a normal age-related amount of neurodegeneration.
If neurodegenerative abnormalities are uncommon in, and probably epiphenomenal to, schizophrenia, it begs the question as to what is the pathology of the disorder and how the macroscopic findings are explained at the microscopic level. The answer has been sought in the cytoarchitecture of the cerebral cortex, with measurements of parameters such as the size, location, distribution, and packing density of neurones and their synaptic connections (31> (Table,2).
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