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Conversion to Mild Cognitive Impairment and Alzheimer’s Disease Dementia Related to Apathy, APOE Genotype and Antidepressant Use
Rubina A. Malik, Miguel Restrepo Martinez, Isis So, Elizabeth C. Finger, for the Alzheimer’s Disease Neuroimaging Initiative. Journal of Geriatric Psychiatry and Neurology, 2025-04-14
Topic: Amyloid, tau and blood-test diagnosis
Objective Apathy 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. Methods Participants 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. Results Apathy 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. Conclusion Our 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.
Key findings
- Results Apathy 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.
- Conclusion Our findings support apathy and APOE ε4 as robust predictors of conversion to MCI and ADD, and demonstrate novel associations between antidepressant use and conversion.
Why it matters
Apathy and the APOE ε4 genotype were associated with increased risk of conversion from cognitively normal to mild cognitive impairment and from mild cognitive impairment to Alzheimer's disease dementia, and antidepressant use was also associated with conversion. These are risk associations, not a treatment or cure.
Study details
- Evidence strengthLow
How this study scored 31/100
Published in a peer-reviewed journal. Scored zero for study design, sample size, effect reported, studied in people and randomised / blinded because the record does not state it. We have no data on senior author's track record, so that was left out: it earned 30 of the 96 points we could judge it on, which is 31 out of 100.
| Component | Points | Why |
|---|---|---|
| Journal tier | 7 / 10 | Tier 3 — peer-reviewed journal (Journal of Geriatric Psychiatry and Neurology) |
| Journal's citation record | 1 / 4 | Journal of Geriatric Psychiatry and Neurology: journal h-index 105 (OpenAlex, 2026-10-29) |
| Study design | 0 / 12 | No study design recorded — scores zero, not guessed (not stated in the record — scored 0) |
| Strength of evidence | 1 / 5 | Rated “low” in our summary |
| Peer-review validation | 10 / 10 | Peer-reviewed. Published as an article in a named peer-reviewed journal. |
| How recent | 4 / 5 | 2025 — within 3 year(s) of the newest study here |
| Sample size | 0 / 4 | Participant count not stated — scores zero (not stated in the record — scored 0) |
| Effect reported | 0 / 3 | No effect size reported — scores zero (not stated in the record — scored 0) |
| Studied in people | 0 / 3 | Not stated whether this was studied in people — scores zero (not stated in the record — scored 0) |
| Randomised / blinded | 0 / 2 | No randomisation or blinding stated — scores zero (not stated in the record — scored 0) |
| Times cited | 1 / 7 | Cited 1 times (OpenAlex, 2026-10-10) |
| Citations per year | 0 / 5 | 0.3 citations a year over 3 year(s) since 2025 |
| Impact for its field and year | 1 / 6 | Cited 0.6× the average for papers of its field and year (OpenAlex FWCI) |
| Cited by studies here | 0 / 6 | No other study in this library cites it |
| Still being cited | 0 / 4 | Cited 1 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | — / 4 | Senior author's record not available — left out of this score |
| Institution's track record | 1 / 3 | Western University: institution h-index 899 (OpenAlex) |
| Multi-centre collaboration | 0 / 3 | OpenAlex lists 1 institution(s) in 1 country — scores zero (affiliation lists can be incomplete) |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 40227643) |
| Free to read | 2 / 2 | Free to read |
| Points | 30 / 96 | Scored on 19 of 20 parts. We have no data for the rest, so they are left out: 30 of the 96 points we could judge it on is 31 out of 100. |
| Total | 31 / 100 | — |
What each of these 20 components measures, and what this score is not →
Read the original
- DOI: 10.1177/08919887251335002
- PubMed: 40227643
- Original source →
- Free full text: Journal of Geriatric Psychiatry and Neurology →
Full text: free to read — OpenAlex lists this copy as free to read: the link above (checked 6 Feb 1020).
Cite this study APA, Vancouver, BibTeX · download .bib or .ris
Built from the record alzhub holds for this paper, not looked up. Volume, issue and page numbers are not held in the record. Check the citation against the original before you use it.
APA 7th
Malik, R. A., Martinez, M. R., So, I., Finger, E. C., & Alzheimer’s Disease Neuroimaging Initiative. (2025). Conversion to Mild Cognitive Impairment and Alzheimer’s Disease Dementia Related to Apathy, APOE Genotype and Antidepressant Use. Journal of Geriatric Psychiatry and Neurology. https://doi.org/10.1177/08919887251335002
Vancouver
Malik RA, Martinez MR, So I, Finger EC, Alzheimer’s Disease Neuroimaging Initiative. Conversion to Mild Cognitive Impairment and Alzheimer’s Disease Dementia Related to Apathy, APOE Genotype and Antidepressant Use. Journal of Geriatric Psychiatry and Neurology. 2025. doi:10.1177/08919887251335002. PMID: 40227643.
BibTeX
@article{malik2025-40227643,
author = {Malik, Rubina A. and Martinez, Miguel Restrepo and So, Isis and Finger, Elizabeth C. and {Alzheimer’s Disease Neuroimaging Initiative}},
title = {{Conversion to Mild Cognitive Impairment and Alzheimer’s Disease Dementia Related to Apathy, APOE Genotype and Antidepressant Use}},
journal = {Journal of Geriatric Psychiatry and Neurology},
year = {2025},
doi = {10.1177/08919887251335002},
pmid = {40227643},
url = {https://doi.org/10.1177/08919887251335002}
}
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