Dementia in Severe Schizophrenia

Topic: Risk, prevention and care in population studies

In this study's cohort of 155 individuals with SETRS (mean [SD] age, 59.3 [10.3] years; 56 female participants [36.1%]), 153 of 155 (98.7%) scored below the cutoff of 26 for mild cognitive impairment, and 73 of 155 (47.1%) scored below the cutoff of 10 for severe dementia (mean [SD] MoCA score, 9.8 [6.4]). At the item level, the MoCA profile of SETRS differed from those of AD and FTD but paralleled that of community-dwelling individuals with schizophrenia (Pearson r = 0.86; P < .001). No participants carried pathogenic variants in mendelian dementia genes; APOE4 allele frequency was significantly lower in SETRS (14.4%) than in AD (33.6%; odds ratio [OR], 0.33; 95% CI, 0.20-0.53; P < .001) or LBD (24.7%; OR, 0.51; 95% CI, 0.29-0.89; P = .01). Cognitive impairment was not attributable to premorbid intellectual disability, poor effort, medications, cardiometabolic risk factors, or institutionalization. Conclusions and Relevance: In this cohort study of 155 individuals with SETRS, none of the commonly proposed explanations for schizophrenia dementia (eg, comorbid Alzheimer disease or cardiovascular risk factors) proved viable. The pattern of cognitive impairments differed from those of Alzheimer disease, frontotemporal dementia, and Lewy body dementia, but recapitulated and intensified that of community-dwelling schizophrenia.

Key findings

• In this study's cohort of 155 individuals with SETRS (mean [SD] age, 59.3 [10.3] years; 56 female participants [36.1%]), 153 of 155 (98.7%) scored below the cutoff of 26 for mild cognitive impairment, and 73 of 155 (47.1%) scored below the cutoff of 10 for severe dementia (mean [SD] MoCA score, 9.8 [6.4]).
• At the item level, the MoCA profile of SETRS differed from those of AD and FTD but paralleled that of community-dwelling individuals with schizophrenia (Pearson r = 0.86; P < .001).
• No participants carried pathogenic variants in mendelian dementia genes; APOE4 allele frequency was significantly lower in SETRS (14.4%) than in AD (33.6%; odds ratio [OR], 0.33; 95% CI, 0.20-0.53; P < .001) or LBD (24.7%; OR, 0.51; 95% CI, 0.29-0.89; P = .01).
• Cognitive impairment was not attributable to premorbid intellectual disability, poor effort, medications, cardiometabolic risk factors, or institutionalization.
• Conclusions and Relevance: In this cohort study of 155 individuals with SETRS, none of the commonly proposed explanations for schizophrenia dementia (eg, comorbid Alzheimer disease or cardiovascular risk factors) proved viable.

Why it matters

In this cohort of 155 individuals with severe schizophrenia, most scored below cutoffs for mild cognitive impairment or severe dementia, and their cognitive pattern differed from Alzheimer's disease and other dementias. The study found no evidence that comorbid Alzheimer's disease or cardiovascular risk factors explained the impairment, and it does not address treating, curing or preventing Alzheimer's disease.

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Study details

• Study designcohort study
• Participants155
• Effect size36.1%; 98.7%; 47.1%
• Evidence strengthModerate

Read the original

• DOI: 10.1001/jamapsychiatry.2026.0171
• PubMed: 41920573
• Original source →
• Free full text: PubMed Central →

Full text: free to read — OpenAlex lists this copy as free to read: the link above (checked 6 Feb 1020).

@article{pathak2026-41920573,
  author  = {Pathak, Ujval S. and Mehralizade, Aydan and Goldberg, Terry E. and Zoghbi, Anthony William},
  title   = {{Dementia in Severe Schizophrenia}},
  journal = {JAMA Psychiatry},
  year    = {2026},
  doi     = {10.1001/jamapsychiatry.2026.0171},
  pmid    = {41920573},
  url     = {https://doi.org/10.1001/jamapsychiatry.2026.0171}
}

Studies this one cites

Referenced by this study and also in the alzhub library, so you can read them here.

• Diagnostic accuracy of the Montreal Cognitive Assessment (MoCA) for cognitive screening in old age psychiatry: Determining cutoff scores in clinical practice. Avoiding spectrum bias caused by healthy controls International journal of geriatric psychiatry · 2019-12-27 · usefulness score 65/100 · Cognitive tests and assessment
• Neuropsychological decline in schizophrenia from the premorbid to the postonset period: evidence from a population-representative longitudinal study The American journal of psychiatry · 2014-01-01 · usefulness score 63/100 · Mild cognitive impairment
• The Montreal Cognitive Assessment, MoCA: a brief screening tool for mild cognitive impairment Journal of the American Geriatrics Society · 2005-04-01 · usefulness score 60/100 · Getting a diagnosis
• The Clinical Dementia Rating (CDR) Neurology · 1993-11-01 · usefulness score 59/100 · Cognitive tests and assessment
• Survival in frontotemporal dementia Neurology · 2003-08-01 · usefulness score 57/100 · Getting a diagnosis

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• Validity of the CogState brief battery: relationship to standardized tests and sensitivity to cognitive impairment in mild traumatic brain injury, schizophrenia, and AIDS dementia complex Archives of clinical neuropsychology : the official journal of the National Academy of Neuropsychologists · 2009-03-25 · usefulness score 49/100
• Postmortem evidence of structural brain changes in schizophrenia. Differences in brain weight, temporal horn area, and parahippocampal gyrus compared with affective disorder Archives of general psychiatry · 1986-01-01 · usefulness score 49/100
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• The relationship between brain structure and neurocognition in schizophrenia: a selective review Schizophrenia research · 2004-10-01 · usefulness score 41/100

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