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Longitudinal associations between neuropsychiatric symptoms, structural and perfusion MRI changes in older adults with Mild Cognitive Impairment
Lombardi G, Leung CC, Burge R, Zelaya F, Bhattacharyya S, Velayudhan L.. medRxiv, 2026-10-19
Topic: Brain imaging, connectivity and assessment
Neuropsychiatric symptoms (NPS) are highly prevalent in Mild Cognitive Impairment (MCI), conceptualized as an intermediate clinical state between normal aging and dementia. Although neuroimaging studies have reported associations between NPS and brain alterations in MCI, longitudinal evidence on NPS and their relationship with multimodal MRI measures remains limited. We aimed to investigate (1) longitudinal changes in NPS, volumetric assessment and measurement of regional cerebral blood flow (CBF) within the medial temporal lobe (MTL); (2) associations between longitudinal changes in MRI measures and NPS; (3) whether baseline MRI measures predicted longitudinal changes in NPS. Thirty individuals with MCI aged over 65 years were recruited, of whom eighteen followed up for a mean period of 29 ± 8.9 months. There were significant reductions in total grey matter and white matter volumes, together with volume loss in the bilateral hippocampus, bilateral parahippocampal gyrus and right entorhinal cortex (p FDR< 0.05) over the follow up period. Volume loss in the right parahippocampal gyrus was associated with increase in aggression (p FDR <0.01), and CBF increase in the right hippocampus and parahippocampal gyrus was associated with worsening in agitation (p FDR <0.01). Furthermore, lower baseline volume of the right entorhinal cortex was associated with increase in aggression, and lower baseline CBF in the right hippocampus and parahippocampal gyrus was associated with worsening of agitation (p FDR <0.05). Our findings highlight the importance of identifying NPS in individuals with MCI and the role of structural and perfusion MRI measures as promising biomarkers for monitoring disease progression and improving risk prediction of conversion to dementia.
Key findings
- There were significant reductions in total grey matter and white matter volumes, together with volume loss in the bilateral hippocampus, bilateral parahippocampal gyrus and right entorhinal cortex (p FDR< 0.05) over the follow up period.
- Volume loss in the right parahippocampal gyrus was associated with increase in aggression (p FDR <0.01), and CBF increase in the right hippocampus and parahippocampal gyrus was associated with worsening in agitation (p FDR <0.01).
- Furthermore, lower baseline volume of the right entorhinal cortex was associated with increase in aggression, and lower baseline CBF in the right hippocampus and parahippocampal gyrus was associated with worsening of agitation (p FDR <0.05).
- Our findings highlight the importance of identifying NPS in individuals with MCI and the role of structural and perfusion MRI measures as promising biomarkers for monitoring disease progression and improving risk prediction of conversion to dementia.
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Study details
- Study designlongitudinal study
- Evidence strengthModerate
How this study scored 16/100
Preprint — not yet peer-reviewed. It scored 35 on the same rubric, but non-peer-reviewed sources are capped at 16, so it shows as 16. Scored zero for sample size, effect reported, studied in people and randomised / blinded because the record does not state it. We have no data on 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 and multi-centre collaboration, so those were left out: it earned 22 of the 62 points we could judge it on, which is 35 out of 100.
| Component | Points | Why |
|---|---|---|
| Journal tier | 2 / 10 | Tier 4 — not a peer-reviewed journal (medRxiv) |
| Journal's citation record | 0 / 4 | Not a journal article, so the journal's record does not count |
| Study design | 7 / 12 | A longitudinal study following the same people over time |
| Strength of evidence | 3 / 5 | Rated “moderate” in our summary |
| Peer-review validation | 4 / 10 | Preprint — not yet peer-reviewed. Hosted on a preprint server. |
| 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 | 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 | — / 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 | 1 / 2 | Not in PubMed, but has a DOI |
| Free to read | 0 / 2 | Behind a paywall — scores zero |
| Points | 22 / 62 | Scored on 12 of 20 parts. We have no data for the rest, so they are left out: 22 of the 62 points we could judge it on is 35 out of 100. |
| Total | 35 / 100 | Capped to 16 because this is not a peer-reviewed article. |
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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
Lombardi, G., Leung, C. C., Burge, R., Zelaya, F., Bhattacharyya, S., & Velayudhan, L. (2026). Longitudinal associations between neuropsychiatric symptoms, structural and perfusion MRI changes in older adults with Mild Cognitive Impairment. medRxiv. https://doi.org/10.64898/2026.10.15.26364284
Vancouver
Lombardi G, Leung CC, Burge R, Zelaya F, Bhattacharyya S, Velayudhan L. Longitudinal associations between neuropsychiatric symptoms, structural and perfusion MRI changes in older adults with Mild Cognitive Impairment. medRxiv. 2026. doi:10.64898/2026.10.15.26364284.
BibTeX
@article{lombardi2026-74862252,
author = {Lombardi, G. and Leung, C. C. and Burge, R. and Zelaya, F. and Bhattacharyya, S. and Velayudhan, L.},
title = {{Longitudinal associations between neuropsychiatric symptoms, structural and perfusion MRI changes in older adults with Mild Cognitive Impairment}},
journal = {medRxiv},
year = {2026},
doi = {10.64898/2026.10.15.26364284},
url = {https://doi.org/10.64898/2026.10.15.26364284}
}
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