Prognostic value of neuroinflammation [¹¹C]PK11195 PET on longitudinal cognitive decline and survival up to 15 years after PET in Alzheimer's disease

Abstract Background Neuroinflammation plays a key role in Alzheimer’s disease (AD) pathophysiology. However, whether neuroinflammation has a prognostic effect on disease progression is largely unknown. Therefore, we aim to investigate the role of neuroinflammation as measured using PET on longitudinal cognition and survival. Method We included 29 amyloid‐positive participants (N=10 MCI, N=19 AD dementia) from a historical cohort who underwent dynamic [ 11 C]PK11195 (TSPO) PET to quantify neuroinflammation (Table 1). [ 11 C]PK11195 BP ND was obtained using supervised cluster analysis and quantified in the parietal and temporal cortex. [ 11 C]PK11195 BP ND values were z‐scored to young healthy controls (N=12). Longitudinal MMSE covering a period up to 11 years was used to measure cognitive decline (median: 3.9, range: 0.3‐11.6 years). We used linear mixed models with random intercept and slope corrected for age, sex and education to investigate the effect of neuroinflammation on cognition. Survival data were available for all participants, up to 15.7 years after PET. To examine the influence of neuroinflammation on survival time, we used age, sex, and diagnosis adjusted cox proportional‐hazards models for both regions. Result Demographic characteristics and mean [ 11 C]PK11195 BP ND can be found in table 1. Overall, the group showed a mean annualized decline of ‐1.86±1.42 points on MMSE and had a median survival time of 7.6 years (range: 0.4‐15.7) after PET. Temporal or parietal [ 11 C]PK11195 BP ND did not predict longitudinal MMSE (parietal: β=0.15, p=0.438; temporal: β=‐0.11, p=0.660) (Figure 1). Higher parietal [ 11 C]PK11195 BP ND was marginally associated with shorter survival (HR = ‐0.39, P=0.043) (Figure 2A). There was no significant difference in survival time with higher temporal [ 11 C]PK11195 BP ND (HR= ‐0.42, P=0.053) (Figure 2B). Conclusion In this initial set of analyses covering up to 11 years of cognitive follow‐up and survival information of 15 years after PET, we found preliminary evidence of a shorter survival with increasing parietal neuroinflammation, but no associations between neuroinflammation PET and the rate of cognitive decline. Future research could explore the effect of neuroinflammation PET on more specific cognitive domains and biological measures such as cortical thickness.