Are elderly With Schizophrenia Less Likely to Develop Alzheimer's Disease

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Are elderly With Schizophrenia Less Likely to Develop Alzheimer's Disease

  1. 1. ARE ELDERLY WITH SCHIZOPHRENIA MORE OR LESS LIKELY TO DEVELOP ALZHEIMER’S DISEASE?As patients with schizophrenia live longer, because of better medical management, suicide prevention,appropriate nutrition, etc. we are beginning to face a new phenomenon: elderly patients with chronicschizophrenia developing Alzheimer’s disease. This is a rather artificial comorbidity, possibly anunintended consequence of improved medical care.In many ways schizophrenia can be considered a disease of accelerating aging. It presents with cognitivedeficits and metabolic abnormalities. Schizophrenia is associated with an increase in mortality, resultingin a decrease in average life span of 20%.Patients with schizophrenia show a rapid cognitive decline after the age of 65 in addition to the alreadyexisting cognitive deficit. Clinical studies suggest that severe cognitive impairment is common amongelderly patients with schizophrenia who reside in long-stay psychiatric institutions.The range of cognitive impairments in individuals with schizophrenia is broad, with the more robust andreplicable deficits typically found in the domains of processing speed, episodic memory, workingmemory, and executive function.Amyloid MarkersIn spite of cognitive deficits, most studies failed to find increased amyloid deposits in patients withschizophrenia, even after age 65, leading to the belief, by some, that patients with schizophrenia areprotected from developing Alzheimer’s disease.http://books.google.com/books?id=KcB8lFjoQHkC&pg=PA45&lpg=PA45&dq=(Hans-Gert+Bernstein)+schizophrenia+protective+for+alzheimers&source=bl&ots=YbZBJuSq2P&sig=7YuwrATwRvLdPLcKvwN8cXMrI20&hl=en&sa=X&ei=ChNhUIvfA-242QWHvoGQDQ&ved=0CDIQ6AEwAw#v=onepage&q=(Hans-Gert%20Bernstein)%20schizophrenia%20protective%20for%20alzheimers&f=falseWhat about tau pathology?Increased cerebrospinal fluid tau protein levels are generally considered to provide a sensitive markerof neurodegenerative processes such as Alzheimers disease (AD). Since a more pronounced cognitivedecline has been described in older schizophrenic patients, it has been hypothesized that these patientsmight be at a higher risk of developing AD.In spite of this belief, no significant differences in CSF total tau and phospho-tau levels were found inpatients with schizophrenia and controls.http://www.ncbi.nlm.nih.gov/pubmed/12799749
  2. 2. Is schizophrenia protective for Alzheimer’s disease?Despite the occurrence of similar pathophysiological factors in patients with Alzheimer’s dementia andschizophrenia, there is a lack of increased Alzheimer’s pathology in schizophrenia. But does that meanthat schizophrenia is protective for Alzheimer’s disease? Could there be other factors that areprotective, such as medication, smoking, altered expression of beta or gamma-secretase, insulinreceptors’ dysfunction?Studying the possible protective factors for Alzheimer’s disease in schizophrenia might help elucidatethe pathophysiology of both conditions.Antipsychotic medications: Xu showed that quetiapine protects cultured neurons against oxidativestress induced by beta amyloid, and that quetiapine prevents memory impairment and decreases A betadeposits in a mouse model of Alzheimer’s disease.http://www.ncbi.nlm.nih.gov/pubmed/18554300Tobacco smoking: A majority of individuals with schizophrenia are heavy smokers. Ignoring its adverseeffects, smoking, has been shown to attenuate A beta deposition in some cortical areas.http://www.ncbi.nlm.nih.gov/pubmed/16150123Beta secretase (BACE 1) was shown to be normal in patients with schizophrenia:http://www.ncbi.nlm.nih.gov/pubmed/18790604However presenilin 2 may be lower in schizophrenia:http://www.ncbi.nlm.nih.gov/pubmed/19232479Abnormalities in brain glucose/energy metabolism and insulin signaling: An “insulin-resistant brainstate” has been hypothesized to form the core of the neurodegenerative events that occur inAlzheimer’s disease. Interestingly, patients with schizophrenia often suffer from metabolic syndrome.Treatment with typical and atypical neuroleptics either initiates or further increases the metabolicproblems of many schizophrenics. In post-mortem brains of schizophrenic patients considerablefunctional decrease of insulin receptors as well as disruption of the Akt-dependent insulin signalingsystem have been found.Different pathology domains?About 72% of the patients with schizophrenia show cognitive impairment. Alzheimer’s dementia per seis diagnosed in only 9% while other dementing diseases are diagnosed in 4% of the individuals withschizophrenia. Over all the degree of senile plaques or neurofibrillary tangles was not different in theschizophrenia group compared with nonschizophrenic psychiatric disorders.http://archpsyc.jamanetwork.com/article.aspx?articleid=191033
  3. 3. It seems that the cognitive deficit in schizophrenia has a different pathology at work than the one wefind in Alzheimer’s disease. Indeed although the general memory is comparable between elderlyschizophrenic patients and Alzheimer’s disease patients, there are some differences. For exampledelayed recall and forgetfulness were less impaired, while attention, working memory and executivefunction were more impaired in elderly schizophrenic patients as compared to Alzheimer’s patients.Elderly with schizophrenia scored lower on digit symbol substitution, similarity, picture completion, andblock design (in WISE-R) as compared to Alzheimer’s disease patients.http://www.ncbi.nlm.nih.gov/pubmed/22163230Just like different memory domains are impaired in schizophrenia vs. Alzheimer’s disease, functionalMRI shows different areas of brain tissue loss in the two conditions. Areas with specifically low graymatter volume in AD were distributed within the neocortical associative areas, while in elderlyschizophrenia patients these were confined to the posterior part of the anterior cingulate gyrus.http://www.sciencedirect.com/science/article/pii/S0006322309002248ADONIS SFERA, MD

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