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Encephale. 2009 Sep;35(4):386-93. doi: 10.1016/j.encep.2008.06.008. Epub 2008 Sep 23.

[Is late-onset schizophrenia related to neurodegenerative processes? A review of literature].

[Article in French]

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  • 1Service du Pr Pringuey, clinique de psychiatrie et de psychologie m├ędicale-Abbaye de Saint-Pons, CHU Pasteur, Nice, France.



Since 1943 when, for the first time, M. Bleuler used the term late-onset schizophrenia (LOS) to refer to diagnostic groups gathering some clinical features of schizophrenia, but with onset after the age of 40, opinions on this entity are divided. The main question is whether LOS and schizophrenia, with onset in early adulthood (early-onset schizophrenia EOS), have the same etiopathogeny. This discussion became more complex with the introduction, in 2000, of a new entity, the "very-late-onset schizophrenia-like psychosis" (VLOSP), which took the place of "late paraphrenia" and grouped together schizophrenia, delusional disorders and paranoid psychosis with age of onset after 60 years. Neuropathological processes underlying these entities have not beed determined. In particular, neurodegenerative processes could be explored.


A literature review between 1 January 1995 and 30 April 2008, based on a research on PubMed with the terms "late-onset schizophrenia", "paraphrenia", "late paraphrenia", "VLOSP", and "late psychosis", takes stock of the various studies and hypotheses which have investigated the link between LOS/VLOSP and neurodegenerative processes.


Clinical approach: there is no greater family history of dementia disorders in LOS/VLOSP than in the general population. Neuropsychological pattern between LOS and Alzheimer's disease (AD) seems different, with more impairment in delayed recall in AD, and in short-term memory in LOS. Some longitudinal studies, however, have argued that a part of patients with LOS would develop dementia at 10 years. These patients would have a later onset of disorders (> 60 years). Anatomopathological approach: anatomopathological studies show that LOS is not consecutive to AD, and might be related to a restricted limbic tauopathy. Neuroimaging approach: Magnetic Resonance Imaging (MRI) morphological neuroimaging studies show little differences between LOS and EOS. The thalamus volume was significantly smaller, and cortical atrophy was more important in LOS. MRI neuroimaging studies regarding white matter hyperintensities (WMH), which are considered as a macroscopic manifestation of cerebrovascular disease (CD), show inconsistent results. Positive results are observed with LOS subjects with later onset of disease. In addition, WMH were not located on cerebral tracts, which are implicated in EOS, but were periventricular.


It is notable that the studies conducted do not differentiate between LOS and VLOSP, since these two groups of patients are generally mixed. Furthermore, an attempt to analyse the data has to take into account only the studies which have included subjects with strict criteria of schizophrenia, independently of the disorders' age of onset. In addition, we found no study comparing LOS and Lewy Bodies Dementia, which is however an important differential diagnosis. The two main hypotheses tested appear to be: (1): is LOS a prodrome of AD? (2): is LOS consecutive to CD? This review permits a partial answer to these questions. First, LOS as a prodrome of AD seems very unlikely, considering anatomopathological studies. However, it is possible that subjects with later age of onset of the disease develop dementia at 10 years. Second, CD seems not to be altered by the cerebral tracts which are implicated in EOS. A hypothesis could be that the tracts implicated in LOS and EOS differ. This might explain the differences found in clinical (less formal thought disorders and negative symptoms in LOS compared with EOS) and electroencephalographical studies (no reduction of P300's amplitude in LOS, which has however been proposed as trait marker of schizophrenia in EOS) between LOS and EOS. These tracts could be related to a limbic tauopathy found in anatomopathological studies. More vulnerable subjects would develop LOS with ageing. Other subjects would develop LOS secondary to CD. This could explain the later age of onset of the disease in these subjects.

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