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De Vries et al 1 suggested that dementia in schizophrenia seems to be a real entity with neuropsychological signature similar to that of frontotemporal dementia. This was based on clinical data in eight patients with chronic schizophrenia aged 28 to 64 years presenting with cognitive impairment and evidence of a dementia syndrome not sufficiently explained by their schizophrenic symptoms, However, except for frontal or temporal hypoperfusion on SPECT, they found no characteristic structural imaging abnormalities and, in accordance with Harrison,2 concluded that dementia in elderly schizophrenic patients shows no evidence of any known neurodegenerative disorder and, therefore, requires novel neuropathological explanation. Several recent postmortem studies on such patients showed no excess of Alzheimer's disease or other organic dementing syndromes. This is in line with a personal retrospective study of 99 consecutive necropsy cases of schizophrenic patients aged over 55 (mean age 69.5 (SD 8.25) years) with mean duration of illness of 35.15 (SD 10.1) years, 56% with clinical signs of moderate to severe dementia, where we found a total incidence of definite and probable Alzheimer's disease (using CERAD criteria and Braak staging) of 7.1%, or of 8.7% for those over the age of 65 years. In addition, there was one case each with multi-infarct encephalpathy and Parkinson's disease pathology, and 11 brains showed a lacunary state in the basal ganglia.3Brain weight in demented elderly schizophrenic patients was significantly lower (mean 1119.5 (SD 106.1) g) than in non-demented ones (mean 1216.3 (SD 36.2) g; p<0.001). These data are in line with previous studies showing that cognitive decline in chronic schizophrenic patients seems best related to loss in brain weight, decrease in brain length, and increased ventricular size.4 5 However, demented patients in our cohort were significantly older (mean age 73.36 (SD 6.85)v 64.02 (SD 6.54) years; p<0.001), and had a significantly longer duration of illness (mean 41.1v 28.9 years; p<0.001), suggesting a progressive cognitive decline with both age and duration of the disorder. This, at least in part, could be explained by recent studies demonstrating reduction of synaptophysin (a synaptic plasma membrane protein) immunoreactivity in the prefrontal cortex6 and significant negative correlations between age and concentrations of synaptic plasma membrane proteins and syntax in mRNA in the temporal cortex of schizophrenic patients7 reflecting abnormalities in synaptic connectivity; this may cause functional impairment of the limbic circuitry that is thought to be central in the integration of behaviour and cognition.3 These findings are consistent with the hypothesis that changes in synaptic function in both prefrontal or limbic circuits in patients with chronic schizophrenia may contribute to the pathophysiology including cognitive dysfunctions in this disorder.3 7 8 However, future prospective clinicopathological and molecular genetic studies using validated methods are necessary to elucidate the bases of cognitive impairment and dementia in chronic schizophrenic patients.
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