Persistent neuropsychiatric symptoms (NPS) in older adults could serve as early warning signs of underlying Alzheimer’s disease (AD) pathology, according to new research. The study, analyzing data from over 1,000 participants, emphasizes the importance of monitoring mood and behavioral changes in seniors as potential precursors to Alzheimer’s dementia.
Researchers investigated whether mild behavioral impairment (MBI), defined as later-life, emergent, and persistent NPS, was associated with the presence of AD pathology confirmed at autopsy. The study included 1,016 older adults without dementia at baseline, with an average age of 82.6 years. MBI status was determined based on symptom persistence across more than two-thirds of pre-dementia study visits.
The findings revealed that individuals with AD pathology were 88.4% more likely to have exhibited MBI approximately five years before death compared to those without AD pathology (odds ratio [OR]: 1.88; 95% confidence interval [CI]: 1.29-2.75; p<0.01). Notably, the likelihood of having non-persistent NPS without MBI did not differ significantly between AD-positive and AD-negative participants. The study further explored the relationship between MBI and other neuropathologies, including Lewy body disease (LBD) and TDP-43 proteinopathy, finding no significant associations with MBI status. However, survival analysis demonstrated that MBI-positive individuals had a two-fold increased risk of progressing to AD dementia compared to those without NPS (hazard ratio [HR]: 2.03; 95% CI: 1.60-2.57; p<0.01). This risk was particularly pronounced in participants with normal cognition at baseline, who showed a three-fold increased progression rate to dementia (HR: 3.05; 95% CI: 1.37-6.80; p<0.01). In contrast, those with mild cognitive impairment (MCI) at baseline had a lower but still significant risk (HR: 1.93; 95% CI: 1.51-2.47; p<0.01). Additionally, the presence of limbic LBD intensified the association between MBI and dementia progression. These findings underscore the potential value of incorporating MBI assessments into clinical frameworks for dementia risk evaluation. Identifying behavioral symptoms as early markers of AD pathology could enhance patient selection for disease-modifying treatments. Reference: Sharif SF, Guan DX, Bodnar T, Joseph JT, Zetterberg H, Smith EE, Ismail Z. Neuropsychiatric symptoms and progression to pathologically confirmed Alzheimer's disease. Brain. 2025;awaf156.
