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

## TL;DR

This study identifies different patterns of neuropsychiatric symptoms in dementia and preclinical stages, showing how health factors like metabolism and weight are linked to these patterns.

## Contribution

The study reveals distinct neuropsychiatric symptom clusters in preclinical and clinical dementia stages and their associations with metabolic and clinical factors.

## Key findings

- Four distinct neuropsychiatric symptom clusters were identified across dementia and dementia-free groups.
- Lipid abnormalities, glycemic control, thyroid dysfunction, and underweight status are differentially associated with symptom clusters.
- Neuropsychiatric symptoms are present in 42% of preclinical dementia cases, suggesting behavioral changes precede cognitive decline.

## Abstract

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.

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.

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.

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.

Distinct NPS clusters show unique patterns across preclinical and clinical dementia stage.NPSs are common in preclinical stages (42%), suggesting behavioral changes may precede cognitive impairment.Depression‐anxiety‐apathy clusters span dementia stages, while others are stage‐specific.Underweight and hypothyroidism are linked to complex, psychosis‐like NPS clusters.Dyslipidemia is a shared feature across clusters; female sex and altered glycemia show stage‐specific associations.

Distinct NPS clusters show unique patterns across preclinical and clinical dementia stage.

NPSs are common in preclinical stages (42%), suggesting behavioral changes may precede cognitive impairment.

Depression‐anxiety‐apathy clusters span dementia stages, while others are stage‐specific.

Underweight and hypothyroidism are linked to complex, psychosis‐like NPS clusters.

Dyslipidemia is a shared feature across clusters; female sex and altered glycemia show stage‐specific associations.