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 chronic
schizophrenia developing Alzheimer’s disease. This is a rather artificial comorbidity, possibly an
unintended consequence of improved medical care.
In many ways schizophrenia can be considered a disease of accelerating aging. It presents with cognitive
deficits and metabolic abnormalities. Schizophrenia is associated with an increase in mortality, 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 the already
existing cognitive deficit. Clinical studies suggest that severe cognitive impairment is common among
elderly 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 and
replicable deficits typically found in the domains of processing speed, episodic memory, working
memory, and executive function.
Amyloid Markers
In spite of cognitive deficits, most studies failed to find increased amyloid deposits in patients with
schizophrenia, even after age 65, leading to the belief, by some, that patients with schizophrenia are
protected 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=7YuwrATw
RvLdPLcKvwN8cXMrI20&hl=en&sa=X&ei=ChNhUIvfA-
242QWHvoGQDQ&ved=0CDIQ6AEwAw#v=onepage&q=(Hans-
Gert%20Bernstein)%20schizophrenia%20protective%20for%20alzheimers&f=false
What about tau pathology?
Increased cerebrospinal fluid tau protein levels are generally considered to provide a sensitive marker
of neurodegenerative processes such as Alzheimer's disease (AD). Since a more pronounced cognitive
decline has been described in older schizophrenic patients, it has been hypothesized 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 were found in
patients with schizophrenia and controls.
http://www.ncbi.nlm.nih.gov/pubmed/12799749

2. Is schizophrenia protective for Alzheimer’s disease?
Despite the occurrence of similar pathophysiological factors in patients with Alzheimer’s dementia 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 be other factors that are
protective, such as medication, smoking, altered expression of beta or gamma-secretase, insulin
receptors’ dysfunction?
Studying the possible protective factors for Alzheimer’s disease in schizophrenia might help elucidate
the pathophysiology of both conditions.
Antipsychotic medications: Xu showed that quetiapine protects cultured neurons against oxidative
stress induced by beta amyloid, and that quetiapine prevents memory impairment and decreases A beta
deposits in a mouse model of Alzheimer’s disease.
http://www.ncbi.nlm.nih.gov/pubmed/18554300
Tobacco smoking: A majority of individuals with schizophrenia are heavy smokers. Ignoring its adverse
effects, smoking, has been shown to attenuate A beta deposition in some cortical areas.
http://www.ncbi.nlm.nih.gov/pubmed/16150123
Beta secretase (BACE 1) was shown to be normal in patients with schizophrenia:
http://www.ncbi.nlm.nih.gov/pubmed/18790604
However presenilin 2 may be lower in schizophrenia:
http://www.ncbi.nlm.nih.gov/pubmed/19232479
Abnormalities in brain glucose/energy metabolism and insulin signaling: An “insulin-resistant brain
state” has been hypothesized to form the core of the neurodegenerative events that occur in
Alzheimer’s disease. Interestingly, patients with schizophrenia often suffer from metabolic syndrome.
Treatment with typical and atypical neuroleptics either initiates or further increases the metabolic
problems of many schizophrenics. In post-mortem brains of schizophrenic patients considerable
functional decrease of insulin receptors as well as disruption of the Akt-dependent insulin signaling
system have been found.
Different pathology domains?
About 72% of the patients with schizophrenia show cognitive impairment. Alzheimer’s dementia per se
is diagnosed in only 9% while other dementing diseases are diagnosed in 4% of the individuals with
schizophrenia. Over all the degree of senile plaques or neurofibrillary tangles was not different in the
schizophrenia group compared with nonschizophrenic psychiatric disorders.
http://archpsyc.jamanetwork.com/article.aspx?articleid=191033

3. It seems that the cognitive deficit in schizophrenia has a different pathology at work than the one we
find in Alzheimer’s disease. Indeed although the general memory is comparable between elderly
schizophrenic patients and Alzheimer’s disease patients, there are some differences. For example
delayed recall and forgetfulness were less impaired, while attention, working memory and executive
function 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, and
block design (in WISE-R) as compared to Alzheimer’s disease patients.
http://www.ncbi.nlm.nih.gov/pubmed/22163230
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 with specifically low gray
matter volume in AD were distributed within the neocortical associative areas, while in elderly
schizophrenia patients these were confined to the posterior part of the anterior cingulate gyrus.
http://www.sciencedirect.com/science/article/pii/S0006322309002248
ADONIS SFERA, MD