Behavioural changes - such as anxiety, depression, irritability, apathy or agitation, collectively known as neuropsychiatric symptoms - may appear long before a dementia diagnosis. A new study from Karolinska Institutet and the University of Perugia, published in Alzheimer's & Dementia, shows that these symptoms form recognizable patterns across older adults ranging from cognitively unimpaired to those with dementia.
The study included 1,234 individuals aged 65 and older who had visited a memory clinic in Perugia, Italy. Neuropsychiatric symptoms were assessed using a standardized interview tool. Strikingly, 42% of participants without dementia already showed such symptoms.
Using machine learning, the researchers identified four distinct neuropsychiatric symptoms profiles: no or very few symptoms; a combination of depression-apathy-anxiety; a profile characterized by depression-anxiety; and, a pattern dominated by delusions-agitation-irritability. These patterns appeared in both individuals with and without dementia, although more pronounced in those with dementia.
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," says 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 suggest 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.
Publication
"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.
