Conversion to Mild Cognitive Impairment and Alzheimer’s Disease Dementia Related to Apathy, APOE Genotype and Antidepressant Use

J Geriatr Psychiatry Neurol. 2025 Apr 14:8919887251335002. doi: 10.1177/08919887251335002. Online ahead of print.

ABSTRACT

ObjectiveApathy and APOE ε4 genotype are risk factors for developing Alzheimer’s disease dementia (ADD). Antidepressant use is known to induce apathy. This study aimed to examine associations between APOE ε4, apathy, and antidepressant use with progression from cognitively normal (CN) to mild cognitive impairments (MCI), and MCI to ADD.MethodsParticipants aged 55-90 were recruited from the Alzheimer’s Disease Neuroimaging Initiative. Participants were CN or had MCI at baseline and had completed at least 3 consecutive study visits. The NPI and NPI-Q apathy subscales were used to index the presence of apathy. Antidepressants used by participants included SSRIs, SNRIs, and AYTADs. Cox proportional hazards analyses examined the combined effects of apathy, APOE ε4 genotype, and antidepressant use on conversion from CN to MCI and from MCI to ADD.ResultsApathy and APOE ε4 were associated with increased risk of conversion along the CN-MCI-ADD continuum. Antidepressant use was associated with progression from MCI to ADD, and progression from CN to MCI in non-apathetic APOE ε4 carriers.ConclusionOur findings support apathy and APOE ε4 as robust predictors of conversion to MCI and ADD, and demonstrate novel associations between antidepressant use and conversion. Future research should explore whether antidepressant use in MCI and ADD causes apathetic symptoms or serves to index apathy/depression severity.

PMID:40227643 | DOI:10.1177/08919887251335002