Changes in mood and behaviour — such as anxiety, depression, irritability or apathy — may start years before dementia is diagnosed.
A new study by researchers from Karolinska Institutet and the University of Perugia suggests these symptoms often follow clear patterns, even in older adults who do not yet have dementia.
The study looked at 1,234 people aged 65 and over attending a memory clinic in Italy and found that 42% of those without dementia were already experiencing such symptoms.
Using machine learning, researchers identified four main patterns, ranging from very few symptoms to combinations involving depression, anxiety, apathy, or more severe signs such as agitation and delusions.
Early behavioural changes
Our results show that neuropsychiatric symptoms—an important dimension of brain health—can appear early and are not only something that emerges in established dementia.
Anna Marseglia, last author and assistant professor at the Department of Neurobiology, Care Sciences and Society, Karolinska Institutet
“This may give us valuable clues about who is at higher risk of progressing to dementia. Also, our study suggests that certain symptom clusters co‑occur with treatable health conditions, highlighting opportunities for preventive strategies and earlier support.”
Indeed, the study identified links across the identified different neuropsychiatric symptoms profiles and modifiable health factors, including high LDL cholesterol, low HDL, poorly regulated blood sugar, thyroid disorders, and underweight.
“Because several of these health conditions are treatable, this opens possibilities for better monitoring and supporting older adults who show early behavioural changes,” says Anna Giulia Guazzarini, visiting PhD student from the University of Perugia within the Westman Neuroimaging research group at KI and first author of the study.
“However, since our study is cross‑sectional, we cannot determine causality”, says Anna Marseglia.
The next step is to follow participants over time to understand how the four symptom profiles progress clinically, and to examine in detail the role of lipids and glucose alterations, thyroid-related and underweight factors in that progression. The researchers also plan to link these behavioural patterns to neuroimaging and blood‑based biomarkers of Alzheimer’s disease and other dementias to understand better the underlying mechanisms.
The study was conducted in collaboration with the University of Perugia, Italy, and funded by the Swedish Research Council, Forte, CIMED, the Alzheimer Foundation, the Dementia Foundation, the Gamla Tjänarinnors Foundation, and several foundations at Karolinska Institutet. The researchers report no conflicts of interest.
25.03.2026.
SOURCE
”Neuropsychiatric symptoms in preclinical and clinically manifest dementia: clusters and their health determinants”, Anna Giulia Guazzarini, Evangelos Galaris, Virginia Boccardi, Francesca Mancinetti, Carmelinda Ruggiero, J-Sebastian Muelboeck, Patrizia Mecocci, Eric Westman, Anna Marseglia, Alzheimer’s & Dementia, online 8 March 2026, doi: 10.1002/alz.71255.
