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Towards the development of a management protocol for subjective cognitive decline: Insights from a cross-sectional and longitudinal analysis of multimodal data from a memory clinic
Salvatore Mazzeo, Michael Lassi, Sonia Padiglioni, Alberto Arturo Vergani, Valentina Moschini, Maenia Scarpino, Giulia Giacomucci, Rachele Burali et al.. Journal of Alzheimer s Disease, 2026-01-28
Topic: Risk, prevention and care in population studies
Background Subjective cognitive decline (SCD) represents the first early symptomatic stage of Alzheimer's disease (AD). Objective We aimed to investigate the relationships between features in SCD and to assess the importance of these features in the future development of dementia to inform a targeted management protocol. Methods 440 SCD patients underwent neurological and neuropsychological assessments, MRI scans, APOE genotyping, and AD biomarker evaluations. Patients were followed for a median of 10 years. Relationships among features were first assessed univariately, focusing on differences across stratified subgroups. To capture multivariate associations, we applied network analysis using a Markov Random Field. Finally, baseline features were related to dementia progression using an XGboost machine learning model. Results Women comprising 68.9% of the cohort, were generally younger at onset, had lower APOE ε4 prevalence, and differed in neuropsychological performance compared to men. Older patients (age >60) exhibited a higher prevalence of APOE ε4 and cerebral small vessel disease. Patients with depressive symptoms demonstrated lower cognitive performance across multiple domains. Network analysis indicated complex interconnections among gender, cognitive reserve, SCD severity, and depressive symptoms. The XGboost model achieved 74% accuracy in predicting progression to dementia, identifying age at onset, mini-mental state examination scores, and APOE genotype as the most predictive factors. Conclusions This study highlights the role of age, gender, APOE genotype, and depressive symptoms in the presentation and progression of cognitive decline. By identifying key predictive features, we propose a personalized management protocol aimed at optimizing care for individuals with SCD. Trial registration number: NCT05569083, registration date: 2019-05-30
Key findings
- Results Women comprising 68.9% of the cohort, were generally younger at onset, had lower APOE ε4 prevalence, and differed in neuropsychological performance compared to men.
- Patients with depressive symptoms demonstrated lower cognitive performance across multiple domains.
Why it matters
In 440 people with subjective cognitive decline followed for a median of 10 years, a machine learning model predicted progression to dementia with 74% accuracy, and features such as gender, cognitive reserve, subjective cognitive decline severity, and depressive symptoms were interconnected. This is a prediction and management-protocol study, not a treatment or cure.
Study details
- Effect size68.9%
- Evidence strengthModerate
How this study scored 44/100
Published in a peer-reviewed journal. Scored zero for study design, sample size, studied in people and randomised / blinded because the record does not state it.
| Component | Points | Why |
|---|---|---|
| Journal tier | 7 / 10 | Tier 3 — peer-reviewed journal (Journal of Alzheimer s Disease) |
| Journal's citation record | 2 / 4 | Journal of Alzheimer s Disease: journal h-index 218 (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 | 3 / 5 | Rated “moderate” in our summary |
| Peer-review validation | 10 / 10 | Peer-reviewed. Published as an article in a named peer-reviewed journal. |
| How recent | 5 / 5 | 2026 — within 1 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 | 2 / 3 | Effect reported as a number, without an interval or test |
| 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 2 times (OpenAlex, 2026-10-10) |
| Citations per year | 1 / 5 | 1.0 citations a year over 2 year(s) since 2026 |
| Impact for its field and year | 4 / 6 | Cited 9.5× 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 2 times in 2024–2026 (2026 still in progress; OpenAlex) |
| Senior author's track record | 2 / 4 | Last-listed author Valentina Bessi: h-index 35 (OpenAlex, whole career) |
| Institution's track record | 1 / 3 | University of Pavia: institution h-index 809 (OpenAlex) |
| Multi-centre collaboration | 2 / 3 | OpenAlex lists 8 institution(s) in 1 country |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 41603334) |
| Free to read | 2 / 2 | Free to read |
| Total | 44 / 100 | — |
What each of these 20 components measures, and what this score is not →
Read the original
- DOI: 10.1177/13872877261416117
- PubMed: 41603334
- Original source →
- Free full text: Florence Research (University of Florence) →
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. The record's author list ends in “et al.”, so not every author is named. Check the citation against the original before you use it.
APA 7th
Mazzeo, S., Lassi, M., Padiglioni, S., Vergani, A. A., Moschini, V., Scarpino, M., et al. (2026). Towards the development of a management protocol for subjective cognitive decline: Insights from a cross-sectional and longitudinal analysis of multimodal data from a memory clinic. Journal of Alzheimer s Disease. https://doi.org/10.1177/13872877261416117
Vancouver
Mazzeo S, Lassi M, Padiglioni S, Vergani AA, Moschini V, Scarpino M, et al. Towards the development of a management protocol for subjective cognitive decline: Insights from a cross-sectional and longitudinal analysis of multimodal data from a memory clinic. Journal of Alzheimer s Disease. 2026. doi:10.1177/13872877261416117. PMID: 41603334.
BibTeX
@article{mazzeo2026-41603334,
author = {Mazzeo, Salvatore and Lassi, Michael and Padiglioni, Sonia and Vergani, Alberto Arturo and Moschini, Valentina and Scarpino, Maenia and Giacomucci, Giulia and Burali, Rachele and others},
title = {{Towards the development of a management protocol for subjective cognitive decline: Insights from a cross-sectional and longitudinal analysis of multimodal data from a memory clinic}},
journal = {Journal of Alzheimer s Disease},
year = {2026},
doi = {10.1177/13872877261416117},
pmid = {41603334},
url = {https://doi.org/10.1177/13872877261416117}
}
Studies this one cites
Referenced by this study and also in the alzhub library, so you can read them here. Showing 12 of 13.