Prediction of cognitive decline in healthy aging based on neuropsychiatric symptoms and PET-biomarkers of Alzheimer's disease

Neuropsychiatric symptoms (NPS) have been associated with a risk of accelerated cognitive decline or conversion to dementia of the Alzheimer's Disease (AD) type. Moreover, the NPS were also associated with higher AD biomarkers (brain tau and amyloid burden) even in non-demented patients. But the effect of the relationship between NPS and biomarkers on cognitive decline has not yet been studied. This work aims to assess the relationship between longitudinal cognitive changes and NPS, specifically depression and anxiety, in association with AD biomarkers in healthy middle-aged to older participants. The cohort consisted of 101 healthy participants aged 50-70 years, 66 of whom had neuropsychological assessments of memory, executive functions, and global cognition at a 2-year follow-up. At baseline, NPS were assessed using the Beck Depression and Anxiety Inventories while brain tau and amyloid loads were measured using positron emission topography. For tau burden, THK5351 uptake is used as a proxy of tau and neuroinflammation. Participants, declining or remaining stable at follow-up, were categorized into groups for each cognitive domain. Group classification was investigated using binary logistic regressions based on combined AD biomarkers and the two NPS. The results showed that an association between anxiety and prefrontal amyloid burden significantly classified episodic memory decline, while the classification of global cognitive decline involved temporal and occipital amyloid burden but not NPS. Moreover, depression together with prefrontal and hippocampal tau burden were associated with a decline in memory. The classification of participants based on executive decline was related to depression and mainly prefrontal tau burden. These findings suggest that the combination of NPS and brain biomarkers of AD predicts the occurrence of cognitive decline in aging.