Potential mechanisms
The narrative review showed that most studies (n = 10) were of high methodological quality, although two were rated as fair and one as poor.
Almost all studies accounted for basic sociodemographic confounders. Several also adjusted for comorbidities, alcohol/substance use disorders, medications, smoking status, and income/education level.
Pooled estimates from the meta-analyzed studies showed that only one showed no significant association between psychotic disorders and dementia, whereas 10 reported increased risk (pooled risk ratio, 2.52; 95% confidence interval, 1.67-3.80; I2, 99.7%).
Subgroup analyses showed higher risk in participants with typical and late-onset psychotic disorders (pooled RR, 2.10; 95% CI, 2.33-4.14; I2, 77.5%; P = .004) vs. those with very late onset schizophrenia-like psychoses (pooled RR, 2.77; 95% CI, 1.74-4.40 I2, 98.9%; P < .001).
The effect was larger in studies with a follow-up of less than 10 years vs. those with a follow-up of 10 years or more, and it was also greater in studies conducted in non-European vs. European countries (all P < .001).
Studies with more female participants (≥ 60%) showed higher risk compared with those that had a lower percentage of female participants. Studies published during or after 2020 showed a stronger association than those published before 2020 (all P < .001).
There was also a higher risk for dementia in studies investigating broader nonaffective psychotic disorders compared with studies investigating only schizophrenia, in prospective vs. retrospective studies, and in studies with a minimum age of less than 60 years at baseline vs. a minimum age of 60 or older (all P < .001).
“Several possible mechanisms could underlie these findings, although we were not able to directly test these in our review,” Dr. Stafford said. She noted that psychotic disorders and other psychiatric diagnoses may cause dementia.
“People with psychotic disorders such as schizophrenia are also at higher risk of health conditions including cardiovascular disease and diabetes, which are known risk factors for dementia and could underpin these associations,” said Dr. Stafford.
It is also possible “that psychotic symptoms could be early markers of dementia for some people, rather than causes,” she added.
Neuroimaging evidence lacking
Commenting on the study, Dilip V. Jeste, MD, former senior associate dean for healthy aging and senior care and distinguished professor of psychiatry and neurosciences at the University of California, San Diego, complimented the investigators for “an excellent article on an important but difficult topic.”
Dr. Dilip V. Jeste
Limitations “pertain not to the meta-analysis but to the original studies,” said Dr. Jeste, who was not involved with the review. Diagnosing dementia in individuals with psychotic disorders is “challenging because cognitive deficits and behavioral symptoms in psychotic disorders may be misdiagnosed as dementia in some individuals – and vice versa,” he added.
Moreover, the studies did not specify the type of dementia, such as Alzheimer’s disease, vascular, Lewy body, frontotemporal, or mixed. Together, “they account for 90% of the dementias, and most patients with these dementias have brain abnormalities that can clearly be seen on MRI,” Dr. Jeste said.
However, patients with schizophrenia who are diagnosed with dementia “rarely show severe brain atrophy, even in specific regions commonly observed in nonpsychotic people with these dementias,” Dr. Jeste noted.
Thus, objective neuroimaging-based evidence for dementia and its subtype “is lacking in most of the published studies of persons with psychotic disorders diagnosed as having dementia,” he said.
There is a “clear need for comprehensive studies of dementia in people with psychotic disorders to understand the significance of the results,” Dr. Jeste concluded.
The review did not receive any funding. Dr. Stafford was supported by an NIHR-UCLH BRC Postdoctoral Bridging Fellowship and the National Institute for Health Research Biomedical Research Centre at University College London Hospitals NHS Foundation Trust. Dr. Stafford was also the principal investigator in one of the studies meeting the inclusion criteria of the review. The other investigators and Dr. Jeste reported no relevant financial relationships.
A version of this article first appeared on Medscape.com.