Psychotic Disorders as a Potentially Modifiable Risk Factor for Dementia

Nonaffective psychotic disorders are an important, potentially modifiable risk factor for all-cause dementia, with individuals with these disorders warranting close monitoring for cognitive decline in later life, according to study results published in Psychological Medicine.

Recognizing that research in this area is limited, researchers sought to systematically review and to quantify the risk for dementia associated with psychotic disorders. They searched several electronic databases for published literature that had investigated nonaffective psychotic disorders and subsequent dementia. Both prospective and longitudinal studies were included.

The population of interest comprised adults aged 18 years and older with a clinical diagnosis of a nonaffective psychotic disorder; the comparison group included adults without a nonaffective psychotic disorder. The study selection process followed the Preferred Reporting Items for Systematic Reviews and Meta-analysis (PRISMA). Random-effects meta-analyses were used to pool estimates across studies; the risk for bias was evaluated for each study.

A total of 13 studies were included in the meta-analysis, 3 of which were prospective and 10 of which were retrospective. The studies were published between 2003 and 2022 (4 from 2003-2014, 4 from 2015 and 2019, and 5 from 2015 or later). Sample size in the studies ranged from 61 to 8,011,773 participants, with a total of 12,997,101 participants overall.

The researchers found nonaffective psychotic disorders were associated with an increased risk for all-cause dementia (pooled risk ratio [RR], 2.52; 95% CI, 1.67-3.80; n=12,997,101; P <.001). In all, 11 of the studies demonstrated high heterogeneity between the studies.

Based on subgroup analyses, a stronger association between nonaffective psychotic disorders was observed in studies with shorter follow-up periods, which were conducted in non-European countries, were published after 2020, and had a study sample in which 60% or more of the participants were women.

The risk for dementia was higher among:

• Individuals aged 60 years or younger at baseline
• Individuals with typical and late-onset psychotic disorders vs those with very late-onset psychosis
• Individuals with broader psychotic disorders than schizophrenia
• Individuals in prospective vs retrospective studies

Following the exclusion of low-quality studies, the associations remained (pooled RR, 2.50; 95% CI, 1.71-3.68: P <.001).

Several study limitations warrant mention. To begin, diagnosing dementia in individuals with psychotic disorders is challenging. In those with psychotic disorders, cognitive deficits and behavioral symptoms may be misdiagnosed as dementia, whereas in other instances, symptoms of dementia could be misattributed as being symptoms of psychosis. Further, insufficient data were available to conduct formal subgroup analyses for all of the factors of interest, including the interval between onset of psychotic disorder and diagnosis of dementia, as well as age at onset of dementia, thus underscoring the need for additional longitudinal data in this area.

“Our findings indicate that psychotic disorders are a potentially modifiable risk factor for dementia and suggest that individuals with psychotic disorders need to be closely monitored for cognitive decline in later life,” the researchers acknowledged.

They added that “Given the robust association observed between psychotic disorders and future dementia risk, [these] findings should be reflected in future clinical guidelines for the treatment and care of people living with [nonaffective] psychotic disorders.”

Disclosure: One of the study authors has declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of the author’s disclosures.