This document discusses whether elderly patients with schizophrenia are more or less likely to develop Alzheimer's disease. While schizophrenia is associated with accelerated cognitive decline in elderly patients, most studies have failed to find increased amyloid deposits or cerebrospinal fluid markers of Alzheimer's pathology in elderly schizophrenia patients. Some potential protective factors for Alzheimer's in schizophrenia patients are discussed, such as effects of antipsychotic medications, tobacco smoking, and abnormalities in brain insulin signaling and glucose metabolism. The cognitive deficits seen in elderly schizophrenia differ from those in Alzheimer's, and structural brain imaging also shows different patterns of tissue loss between the two conditions. In conclusion, while cognitive impairment is common in elderly schizophrenia, they do not appear to have an increased risk of progressive Alzheimer's

1. Are Elderly with Schizophrenia More or Less Likely to
Develop Alzheimer’s disease?
Adonis Sfera*
President, South Coast Clinical Trials, Anaheim, California, CA, USA
Correspondence:
Dr. Adonis Sfera
South Coast Clinical Trials
3400 W. Ball rd, suite 100
Anaheim, CA, 92804, USA
Dr.sfera@gmail.com

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Are Elderly with Schizophrenia More or Less Likely to
Develop Alzheimer’s disease?
Adonis Sfera
1. Introduction
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.
2. 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.
3. 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.
4. Is schizophrenia protective for Alzheimer’s disease?

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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.
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.
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-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.
5. 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.
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

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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.
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.
Structural imaging in schizophrenia and Alzheimer’s disease
4. Conclusion
Elderly with schizophrenia are typically seen with rapid cognitive decline and the reason they
lack progressive Alzheimer’s pathology has led to an assumption whether these patients are
resistant to Alzheimer’s dementia. The reasons that elucidate lack of increased frequency of
progressive development of Alzheimer’s disease in elderly with schizophrenia are clearly not
known. Currently, the morphological findings of cognitive decline in elderly schizophrenics have
been debated. Recent studies, contrary to the previous findings, demonstrated that these patients
had no increased frequency of Alzheimer’s disease (AD) pathology.

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Conflict of interest:
There is no conflict of interest with respect to this article.