Behavioral changes such as anxiety, depression, irritability, apathy, or agitation—collectively known as neuropsychiatric symptoms—may manifest long before a formal dementia diagnosis, according to a recent study by Karolinska Institutet and the University of Perugia. Published in the journal Alzheimer’s & Dementia, the research highlights that these symptoms form distinct patterns in older adults, ranging from those who are cognitively unimpaired to those diagnosed with dementia.
The study involved 1,234 individuals aged 65 and older who visited a memory clinic in Perugia, Italy. Using a standardized interview tool, researchers assessed neuropsychiatric symptoms and found that a striking 42% of participants without dementia already exhibited such symptoms. The findings suggest that these early behavioral changes could serve as indicators of increased dementia risk.
Recognizing Patterns in Neuropsychiatric Symptoms
Leveraging machine learning, the researchers identified four distinct profiles of neuropsychiatric symptoms: no or very few symptoms; a combination of depression, apathy, and anxiety; a profile characterized by depression and anxiety; and a pattern dominated by delusions, agitation, and irritability. These profiles were evident in both individuals with and without dementia, though they were more pronounced in those with the condition.
“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,” said 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.”
Linking Symptoms to Modifiable Health Factors
The study also identified connections between the different neuropsychiatric symptom profiles and modifiable health factors, such as high LDL cholesterol, low HDL, poorly regulated blood sugar, thyroid disorders, and being underweight. These findings underscore the potential for better monitoring and support for older adults exhibiting early behavioral changes.
“Because several of these health conditions are treatable, this opens possibilities for better monitoring and supporting older adults who show early behavioral changes,” noted Anna Giulia Guazzarini, a visiting PhD student from the University of Perugia and first author of the study.
Future Research Directions
Despite the promising findings, the study’s cross-sectional nature means causality cannot be established. As a next step, the researchers plan to follow participants over time to understand how the four symptom profiles progress clinically. They also aim to examine the role of lipids, glucose alterations, thyroid-related factors, and underweight conditions in this progression.
Moreover, the research team intends to link these behavioral patterns to neuroimaging and blood-based biomarkers of Alzheimer’s disease and other dementias to gain a deeper understanding of the underlying mechanisms.
The study was conducted in collaboration with the University of Perugia, Italy, and was 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 have reported no conflicts of interest.
The findings offer a fresh perspective on the early detection of dementia and emphasize the importance of addressing modifiable health factors that may contribute to neuropsychiatric symptoms. As research continues, these insights could pave the way for more effective preventive strategies and interventions for those at risk.
