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Longitudinal associations between neuropsychiatric symptoms, structural and perfusion MRI changes in older adults with Mild Cognitive Impairment

Early results, not yet checked by other scientists · medRxiv · Oct 19, 2026

What this means

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.

A plain-English summary is on its way. Until then, this is the start of the authors' own summary.

Tested inNot stated
Who it was tested in
Not stated
Kind of research
Early results, not yet checked by other scientists

The science

Original title
Longitudinal associations between neuropsychiatric symptoms, structural and perfusion MRI changes in older adults with Mild Cognitive Impairment
Authors
Lombardi, G., Leung, C. C.-Y., Burge, R. et al.
Journal
medRxiv (preprint, not yet peer reviewed)
Published
Oct 19, 2026
Study type
Preprint

Abstract

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 (pFDR[&le;]0.05) over the follow up period. Volume loss in the right parahippocampal gyrus was associated with increase in aggression (pFDR<0.01), and CBF increase in the right hippocampus and parahippocampal gyrus was associated with worsening in agitation (pFDR<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 (pFDR<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.

Read it on medRxiv ↗

Lombardi, G., Leung, C. C.-Y., Burge, R. et al. 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. https://doi.org/10.64898/2026.10.15.26364284

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