Are elderly with schizophrenia more or less likely to (docx) (1)
Are Elderly with Schizophrenia More or Less Likely toDevelop Alzheimer’s disease?Adonis Sfera*President, South Coast Clinical Trials, Anaheim, California, CA, USACorrespondence:Dr. Adonis SferaSouth Coast Clinical Trials3400 W. Ball rd, suite 100Anaheim, CA, 92804, USADr.email@example.com
Sfera 1Are Elderly with Schizophrenia More or Less Likely toDevelop Alzheimer’s disease?Adonis Sfera1. IntroductionAs patients with schizophrenia live longer, because of better medical management, suicideprevention, appropriate nutrition, etc. we are beginning to face a new phenomenon: elderlypatients with chronic schizophrenia developing Alzheimer’s disease. This is a rather artificialcomorbidity, possibly an unintended consequence of improved medical care.In many ways schizophrenia can be considered a disease of accelerating aging. It presents withcognitive deficits and metabolic abnormalities. Schizophrenia is associated with an increase inmortality, resulting in a decrease in average life span of 20%.Patients with schizophrenia show a rapid cognitive decline after the age of 65 in addition to thealready existing cognitive deficit. Clinical studies suggest that severe cognitive impairment iscommon among elderly patients with schizophrenia who reside in long-stay psychiatricinstitutions.The range of cognitive impairments in individuals with schizophrenia is broad, with the morerobust and replicable deficits typically found in the domains of processing speed, episodicmemory, working memory, and executive function.2. Amyloid MarkersIn spite of cognitive deficits, most studies failed to find increased amyloid deposits in patientswith schizophrenia, even after age 65, leading to the belief, by some, that patients withschizophrenia are protected from developing Alzheimer’s disease.3. What about tau pathology?Increased cerebrospinal fluid tau protein levels are generally considered to provide a sensitivemarker of neurodegenerative processes such as Alzheimers disease (AD). Since a morepronounced cognitive decline has been described in older schizophrenic patients, it has beenhypothesized that these patients might be at a higher risk of developing AD.In spite of this belief, no significant differences in CSF total tau and phospho-tau levels werefound in patients with schizophrenia and controls.4. Is schizophrenia protective for Alzheimer’s disease?
Sfera 2Despite the occurrence of similar pathophysiological factors in patients with Alzheimer’sdementia and schizophrenia, there is a lack of increased Alzheimer’s pathology in schizophrenia.But does that mean that schizophrenia is protective for Alzheimer’s disease? Could there beother factors that are protective, such as medication, smoking, altered expression of beta orgamma-secretase, insulin receptors’ dysfunction?Studying the possible protective factors for Alzheimer’s disease in schizophrenia might helpelucidate the pathophysiology of both conditions.Antipsychotic medications: Xu showed that quetiapine protects cultured neurons againstoxidative stress induced by beta amyloid, and that quetiapine prevents memory impairment anddecreases A beta deposits in a mouse model of Alzheimer’s disease.Tobacco smoking: A majority of individuals with schizophrenia are heavy smokers. Ignoring itsadverse effects, smoking, has been shown to attenuate A beta deposition in some cortical areas.Beta secretase (BACE 1) was shown to be normal in patients with schizophrenia.However presenilin 2 may be lower in schizophrenia.Abnormalities in brain glucose/energy metabolism and insulin signaling: An “insulin-resistantbrain state” has been hypothesized to form the core of the neurodegenerative events that occur inAlzheimer’s disease. Interestingly, patients with schizophrenia often suffer from metabolicsyndrome. Treatment with typical and atypical neuroleptics either initiates or further increasesthe metabolic problems of many schizophrenics. In post-mortem brains of schizophrenic patientsconsiderable functional decrease of insulin receptors as well as disruption of the Akt-dependentinsulin signaling system have been found.5. Different pathology domains?About 72% of the patients with schizophrenia show cognitive impairment. Alzheimer’sdementia per se is diagnosed in only 9% while other dementing diseases are diagnosed in 4% ofthe individuals with schizophrenia. Over all the degree of senile plaques or neurofibrillarytangles was not different in the schizophrenia group compared with nonschizophrenic psychiatricdisorders.It seems that the cognitive deficit in schizophrenia has a different pathology at work than the onewe find in Alzheimer’s disease. Indeed although the general memory is comparable betweenelderly schizophrenic patients and Alzheimer’s disease patients, there are some differences. Forexample delayed recall and forgetfulness were less impaired, while
Sfera 3attention, working memory and executive function were more impaired in elderly schizophrenicpatients as compared to Alzheimer’s patients. Elderly with schizophrenia scored lower on digitsymbol substitution, similarity, picture completion, and block design (in WISE-R) as comparedto Alzheimer’s disease patients.Just like different memory domains are impaired in schizophrenia vs. Alzheimer’s disease,functional MRI shows different areas of brain tissue loss in the two conditions. Areas withspecifically low gray matter volume in AD were distributed within the neocortical associativeareas, while in elderly schizophrenia patients these were confined to the posterior part of theanterior cingulate gyrus.Structural imaging in schizophrenia and Alzheimer’s disease4. ConclusionElderly with schizophrenia are typically seen with rapid cognitive decline and the reason theylack progressive Alzheimer’s pathology has led to an assumption whether these patients areresistant to Alzheimer’s dementia. The reasons that elucidate lack of increased frequency ofprogressive development of Alzheimer’s disease in elderly with schizophrenia are clearly notknown. Currently, the morphological findings of cognitive decline in elderly schizophrenics havebeen debated. Recent studies, contrary to the previous findings, demonstrated that these patientshad no increased frequency of Alzheimer’s disease (AD) pathology.
Sfera 4References1. HG. Bernstein. et al. “Schizophrenia protective for Alzheimer’s”. Magdeburg, Germany:springer science ed; 2010.2. Schönknecht P, Hempel A.et al. Cerebrospinal fluid tau protein levels in schizophrenia.Heidelberg, Germany: European Archives of psychiatry and neuroscience; 2003 Apr;253(2):100-2.3. Xu H, Wang H, Zhuang L, et al. “Demonstration of an anti-oxidative stress mechanism ofquetiapine: implications for the treatment of Alzheimers disease”. Carbondale, IL, USA:The FEBS Journal; 2008 Jul; 275(14):3718-28.4. Court JA, Johnson M, Religa D, et al. “Attenuation of Abeta deposition in the entorhinalcortex of normal elderly individuals associated with tobacco smoking”. Newcastle uponTyne, UK: Neuropathology and Applied Neurobiology. 2005 Oct; 31(5):522-35.5. Dean B, Soulby A, Evin GM, et al. “Levels of [(3)H]pirenzepine binding in Brodmannsarea 6 from subjects with schizophrenia is not associated with changes in thetranscription factor SP1 or BACE1”. Victoria, Australia: Schizophrenia Research. 2008Dec; 106 (2-3):229-36.6. Zhang J, Chen J, Xu Q, Shen Y. “Does the presenilin 2 gene predispose toschizophrenia”. Beijing, china: Schizophrenia Research. 2009 Apr; 109(1-3):121-9.7. Purohit D,Perl D, et al. “Alzheimer Disease and Related Neurodegenerative Diseases inElderly Patients With Schizophrenia”. New York, USA: Archives of General Psychiatry.1998; 55(3):205-211.8. Kazui H, Yoshida T, Takaya M, et al. “Different characteristics of cognitive impairmentin elderly schizophrenia and Alzheimers disease in the mild cognitive impairment stage”.Osaka, Japan: Dementia and Geriatric Cognitive Disorders Extra. 2011 Jan; 1(1):20-30.9. Frisonia G, Prestiaa A, Adorni A, et al. “In Vivo Neuropathology of Cortical Changes inElderly Persons with Schizophrenia”. Biological Psychiatry 2009; 66(6):578–585.
Sfera 5Conflict of interest:There is no conflict of interest with respect to this article.