Patients With Both Dementia and Severe Mental Illness Experience Faster Cognitive Decline

older man in wheelchair
older man in wheelchair
Researchers analyzed data from the population of 4 South London boroughs to determine the impact of comorbid bipolar disorder and schizophrenia on the cognitive decline in dementia.

Individuals with dementia who have comorbid severe mental illness (SMI), especially bipolar disorder, experience faster decline in cognitive performance than those without comorbid SMI. However, that decline was attenuated when antidepressant medication was included in models, researchers found in a study published in American Journal of Geriatric Psychiatry. Socio-demographic, health behaviors and cardiovascular risk factors also partially explained the faster decline, the researchers said.

The researchers used data from 4718 individuals from the South London and the Maudsley NHS (National Health Service) Foundation Trust (SLaM) Clinical Record Interact Search (CRIS) of populations of four south London boroughs, which are comparable to London in demographic factors. Individuals had primary or secondary diagnosis of dementia from 2007 to 2018, were at least 50 years old at first diagnosis of dementia, and at least 3 recorded Mini-Mental State Examination (MMSE) scores. The MMSE measures cognitive performance with 21 questions on orientation, immediate and delayed recall, naming, spelling and simple arithmetic, and constructional praxis.

Higher scores indicate better cognitive performance. The included individuals happened to have “slightly higher percentages” of Black and Caribbean, were married or cohabiting and had higher levels of education. Medication data came from combined and natural language processing (NLP) derived data, which identified mentions or not of prescribed medications in 3 categories: antipsychotic, antidepressant, and dementia-treatment agents.

The researchers used linear mixed models with random coefficients to examine group differences in cognitive trajectories and investigated associations with covariates and sensitivity analyses. They compared the models, which contained an unknown category when missing values were larger than 30% for a covariate, with cases with complete information. The researchers also ran an analysis in which they restricted the sample to the 1766 individuals who were still alive in 2019 to check and compare for potential bias associated to premature mortality in individuals with SMI.

The researchers found that individuals with comorbid dementia and SMI (20.8, standard deviation (SD): 6.3) had higher MMSE scores than those individuals with solely dementia (19.7, SD: 6.2, P <.05 for both). Current smokers, individuals classified at risk for cardiovascular disease, or those taking dementia or antipsychotic medication were also found to have lower MMSE scores when compared with those that never smoked, were not classified as having a risk of cardiovascular disease (CVD), and not taking dementia or antipsychotic medication. While cognitive decline appeared to accelerate more quickly in individuals with bipolar disorders compared to those with dementia, individuals with schizophrenia had similar trajectories to those who had solely dementia.

Adjusted by socioeconomics, smoking, CVD risk, and all medications, the slope for MMSE trajectories for individuals with dementia and SMI were -0.133 (0.061) [95% confidence interval (CI) [-0.252, -0.014]]. Before adjusting for all medication, solely dementia medication had a slope estimate of -0.152 (0.058) [95% confidence interval (CI): -0.286, -0.057](P <.01), for cognitive trajectory, with solely antipsychotic medication having a slope estimate of -0.144 (0.061) [95% CI: -0.264, -0.025](P <.05), and with solely antidepressant medication being -0.19 (0.059)[95% CI: -0.306, -0.075](P <.01).

Limitations of the study included data on health behaviors being limited to smoking status and potential selection bias associated with limiting the sample to those with at least 3 MMSE scores available as dementia can go undiagnosed in cases of SMI.

“With regards to medication, adjustment for dementia, antipsychotic, and antidepressant medications strongly impacted the association of interest even after accounting for the other covariates considered such as CVD risk,” the authors said.

“When we examined the role of each medication independently, we found that this impact was clear for dementia and antidepressants, the estimates suggest that there could be a greater and potentially protective impact for antipsychotic medication in the case of bipolar disorders.”

Disclosure: Several study authors declared affiliations with the industry. Please see the original reference for a full list of authors’ disclosures.


Bendayan R, Mascio A, Stewart R, Roberts A, Dobson R. Cognitive trajectories in comorbid dementia with schizophrenia or bipolar disorder: The South London and Maudsley NHS Foundation Trust Biomedical Research Centre (SLaM BRC) case register. Am J Geriatr Psychiatry. Published online November 6, 2020. doi:10.1016/j.jagp.2020.10.018

This article originally appeared on Psychiatry Advisor