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

ObjectiveApathy and <i>APOE</i> 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 <i>APOE</i> 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, <i>APOE</i> ε4 genotype, and antidepressant use on conversion from CN to MCI and from MCI to ADD.ResultsApathy and <i>APOE</i> 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 <i>APOE</i> ε4 carriers.ConclusionOur findings support apathy and <i>APOE</i> 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.