Dementia in Severe Schizophrenia

Area of Science:

• Neuroscience
• Psychiatry
• Genetics

Background:

• Dementia occurs 4-20 times more frequently in schizophrenia patients than the general population.
• The causes of dementia in schizophrenia remain largely unexplained.
• Severe, extremely treatment-resistant schizophrenia (SETRS) represents a distinct clinical subgroup.

Purpose of the Study:

• To characterize the cognitive, clinical, and genetic features of dementia in individuals with SETRS.
• To compare these features with various dementia subtypes and healthy controls.
• To investigate potential etiological factors contributing to dementia in this population.

Main Methods:

• Retrospective cohort study of 155 individuals with SETRS hospitalized for 5+ years.
• Cognitive function assessed using the Montreal Cognitive Assessment (MoCA).
• Comparison with National Alzheimer Coordinating Center data (Alzheimer disease, frontotemporal dementia, Lewy body dementia, vascular dementia) and healthy controls.

Main Results:

• 98.7% of SETRS participants showed mild cognitive impairment, and 47.1% had severe dementia (MoCA score < 10).
• The MoCA profile in SETRS differed from Alzheimer disease and frontotemporal dementia but resembled community-dwelling schizophrenia patients.
• No pathogenic variants in mendelian dementia genes were found; APOE4 allele frequency was lower than in Alzheimer disease and Lewy body dementia.

Conclusions:

• Commonly proposed explanations like comorbid Alzheimer disease or cardiovascular risk factors do not explain dementia in SETRS.
• The cognitive impairment pattern in SETRS is distinct from other dementia types but intensified compared to general schizophrenia.
• Further research is needed to understand the unique etiology of dementia in SETRS.