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March 10, 2026Alzheimer s & Dementia0 citationsOpen Access

Neuropsychiatric symptoms in preclinical and clinically manifest dementia: clusters and their health determinants

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AGAnna Giulia GuazzariniEGEvangelos GalarisVBVirginia Boccardi

Key Points

  • The study aims to identify clusters of neuropsychiatric symptoms and their associated health factors in different dementia stages.
  • Analyzed data from 1234 participants in an Italian memory clinic cohort.
  • Employed machine learning techniques, specifically K-means and Elbow method, to identify symptom clusters.
  • Used multinomial logistic regression to assess associations with health factors.
  • Four distinct neuropsychiatric symptom clusters were identified, varying between dementia and dementia-free groups.
  • Profiles indicated different associations with clinical and metabolic factors, such as lipid abnormalities and glycemic control.
  • Findings suggest neuropsychiatric symptoms may precede cognitive decline and have diagnostic significance.

Abstract

Abstract INTRODUCTION Neuropsychiatric symptoms (NPSs) are common in dementia, but their patterns in preclinical stages remain unclear. This study identified NPS clusters and associated health factors in a geriatric clinical population. METHODS We analyzed 1234 participants from the Italian GERIatric COgnitive evaluation memory clinic cohort with Neuropsychiatric Inventory data. Clusters were derived using machine learning (K‐means, Elbow method) separately for dementia and dementia‐free groups. Associations were assessed via multinomial logistic regression. RESULTS In the overall cohort, four NPS clusters emerged: minimal NPS, depression‐anxiety‐apathy, depression‐anxiety, and delusions‐agitation‐irritability. Cluster profiles differed between the dementia and dementia‐free groups. Specific clinical and metabolic factors – lipid abnormalities, glycemic control, thyroid dysfunction, and underweight status – were differentially associated with NPS clusters. DISCUSSION Distinct NPS patterns exist across the dementia continuum. These clusters differ in demographic, cognitive, functional, and metabolic profiles, suggesting NPS may precede cognitive decline and represent syndromic entities with diagnostic relevance. Multidimensional, personalized approaches are needed.

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Cite This Study

Guazzarini et al. (2026) studied this question.

synapsesocial.com/papers/69af95a470916d39fea4d5fahttps://doi.org/10.1002/alz.71255
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