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Combining a computerized cognitive test with serum biomarkers improves detection of early-onset neurodegenerative disorders
Veera Tikkanen, Teemu I Paajanen, Anna-Leena Heikkinen, Eino Solje, Kasper Katisko, Tarja Kokkola, Sari Kärkkäinen, Sanna-Kaisa Herukka et al.. Journal of Alzheimer's disease : JAD, 2025-10-27
Topic: Plasma and spinal-fluid biomarkers
BackgroundEarly diagnosis of early-onset dementia (EOD) is often challenging. Executive dysfunction is a common symptom in EOD, including Alzheimer's disease (AD). Currently, no specific tools for screening EOD at the primary health care exist. The availability of neuropsychological assessment and biomarker analyses is often limited to specialized memory clinics. However, recent advances in blood-biomarkers and better accessible computerized cognitive tests provide new opportunities.ObjectiveTo investigate the ability of serum biomarkers neurofilament light chain and glial fibrillary acidic protein, combined with a novel computerized Flexible Attention Test (FAT) to distinguish early-onset neurodegenerative disorders from other conditions resulting cognitive symptoms in a diagnostically challenging memory clinic population.MethodsCohort consisted of 206 participants with symptom onset ≤65 years and followed up to 24 months: EOD (n = 54, including 29 AD cases), neurological mild cognitive impairment (MCI-n, n = 34), MCI due to other causes (n = 104), and subjective cognitive decline (n = 14). Serum biomarkers were analyzed using single-molecule array, and discriminative accuracy of individual and combined tests was assessed using Receiver Operating Characteristic and discriminant analyses. FAT was compared to traditional neuropsychological tests.ResultsCombining serum biomarkers with cognitive tests were more accurate in detecting EOD and MCI-n from other conditions (area under the curve, AUC = 0.872) compared to each method individually (AUC = 0.633-0.783). Combination of the FAT and serum biomarkers reached 82.1% accuracy, comparable to traditional neuropsychological tests and biomarkers together (82.3%).ConclusionsIntegrating serum biomarkers with computerized FAT offers a promising strategy for screening EOD early and identifying patients for further evaluation.
Key findings
- FAT was compared to traditional neuropsychological tests.ResultsCombining serum biomarkers with cognitive tests were more accurate in detecting EOD and MCI-n from other conditions (area under the curve, AUC = 0.872) compared to each method individually (AUC = 0.633-0.783).
Study details
- Participants54
- Effect sizeAUC = 0.872; AUC = 0.633-0.783; 82.1%
- Evidence strengthLow
How this study scored 55/100
Published in a peer-reviewed journal. Scored zero for study design and randomised / blinded because the record does not state it. We have no data on journal's citation record, times cited, citations per year, impact for its field and year, cited by studies here, still being cited, senior author's track record, institution's track record, multi-centre collaboration and free to read, so those were left out: it earned 31 of the 56 points we could judge it on, which is 55 out of 100.
| Component | Points | Why |
|---|---|---|
| Journal tier | 7 / 10 | Tier 3 — peer-reviewed journal (Journal of Alzheimer's disease : JAD) |
| Journal's citation record | — / 4 | No journal record from OpenAlex — left out of this score |
| 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 | 1 / 4 | 54 participants |
| Effect reported | 3 / 3 | Effect reported with a statistic (interval, p-value, ratio or similar) |
| Studied in people | 3 / 3 | Studied in people (participant count stated) |
| Randomised / blinded | 0 / 2 | No randomisation or blinding stated — scores zero (not stated in the record — scored 0) |
| Times cited | — / 7 | No citation count (not found in OpenAlex) — left out of this score |
| Citations per year | — / 5 | No citation count or no year — left out of this score |
| Impact for its field and year | — / 6 | No field-weighted citation impact (OpenAlex has none yet) — left out of this score |
| Cited by studies here | — / 6 | Not yet checked against this library's citation graph — left out of this score |
| Still being cited | — / 4 | No yearly citation counts — left out of this score |
| Senior author's track record | — / 4 | Senior author's record not available — left out of this score |
| Institution's track record | — / 3 | No institution listed in OpenAlex — left out of this score |
| Multi-centre collaboration | — / 3 | Institutions not listed — left out of this score |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 41143873) |
| Free to read | — / 2 | Access not recorded — left out of this score |
| Points | 31 / 56 | Scored on 10 of 20 parts. We have no data for the rest, so they are left out: 31 of the 56 points we could judge it on is 55 out of 100. |
| Total | 55 / 100 | — |
What each of these 20 components measures, and what this score is not →
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APA 7th
Tikkanen, V., Paajanen, T. I., Heikkinen, A.-L., Solje, E., Katisko, K., Kokkola, T., et al. (2025). Combining a computerized cognitive test with serum biomarkers improves detection of early-onset neurodegenerative disorders. Journal of Alzheimer's disease : JAD. https://doi.org/10.1177/13872877251389224
Vancouver
Tikkanen V, Paajanen TI, Heikkinen A.-L, Solje E, Katisko K, Kokkola T, et al. Combining a computerized cognitive test with serum biomarkers improves detection of early-onset neurodegenerative disorders. Journal of Alzheimer's disease : JAD. 2025. doi:10.1177/13872877251389224. PMID: 41143873.
BibTeX
@article{tikkanen2025-41143873,
author = {Tikkanen, Veera and Paajanen, Teemu I and Heikkinen, Anna-Leena and Solje, Eino and Katisko, Kasper and Kokkola, Tarja and Kärkkäinen, Sari and Herukka, Sanna-Kaisa and others},
title = {{Combining a computerized cognitive test with serum biomarkers improves detection of early-onset neurodegenerative disorders}},
journal = {Journal of Alzheimer's disease : JAD},
year = {2025},
doi = {10.1177/13872877251389224},
pmid = {41143873},
url = {https://doi.org/10.1177/13872877251389224}
}
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