Recent findings indicate that certain behavioral changes may herald early processes related to dementia. A study conducted by researchers at Karolinska Institutet and the University of Perugia revealed that neuropsychiatric symptoms, including anxiety, depression, irritability, apathy, and agitation, can manifest long before a formal dementia diagnosis. This research, published in Alzheimer’s & Dementia on March 8, 2026, assessed a diverse group of older adults, shedding light on potential early indicators of cognitive decline.
The study involved 1,234 individuals aged 65 and over, all of whom had sought assistance at a memory clinic in Perugia, Italy. Researchers utilized standardized interview tools to assess neuropsychiatric symptoms, discovering that a significant 42% of participants without dementia exhibited these symptoms. By employing machine learning techniques, the team identified four distinct profiles of neuropsychiatric symptoms: minimal symptoms; a mix of depression, apathy, and anxiety; a profile dominated by depression and anxiety; and a pattern characterized by delusions, agitation, and irritability. While these patterns were present in both individuals with and without dementia, they were more pronounced among those diagnosed with the condition.
Anna Marseglia, an assistant professor at Karolinska Institutet and the study’s last author, emphasized the importance of these findings: “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. This may give us valuable clues about who is at higher risk of progressing to dementia.”
The study also highlighted significant connections between the identified symptom profiles and modifiable health factors. These include elevated levels of LDL cholesterol, low levels of HDL cholesterol, poorly regulated blood sugar, thyroid disorders, and issues related to being underweight. “Because several of these health conditions are treatable, this opens possibilities for better monitoring and supporting older adults who show early behavioral changes,” stated Anna Giulia Guazzarini, the study’s first author and a visiting PhD student from the University of Perugia.
Despite these groundbreaking insights, the researchers caution against drawing definitive conclusions about causation. Marseglia noted, “Since our study is cross-sectional, we cannot determine causality.” Future research will involve longitudinal studies to track participants over time, aiming to clarify how the identified symptom profiles progress and to examine the roles of lipid and glucose alterations as well as thyroid-related factors.
Additionally, the research team plans to explore the connections between these behavioral patterns and neuroimaging findings alongside blood-based biomarkers associated with Alzheimer’s disease and other forms of dementia. This could lead to a deeper understanding of the underlying mechanisms of dementia.
The study, which was conducted collaboratively with the University of Perugia, received funding from the Swedish Research Council, Forte, CIMED, the Alzheimer Foundation, the Dementia Foundation, the Gamla Tjänarinnors Foundation, and various foundations at Karolinska Institutet. The researchers have declared no conflicts of interest related to the study.
This research not only enhances the understanding of early behavioral indicators related to dementia but also emphasizes the potential for implementing preventative strategies and providing timely support to older adults at risk. The full study is titled “Neuropsychiatric symptoms in preclinical and clinically manifest dementia: clusters and their health determinants.”
