Regional tau PET patterns predict prospective domain‐specific cognitive decline in Alzheimer’s Disease

Abstract

AbstractBackgroundTau‐PET binding patterns are heterogenous, with regional binding showing strong cross‐sectional correlations with domain‐specific cognitive performance and longitudinal correlations with prospective neurodegeneration. The goal of this study was to evaluate whether regional patterns of baseline tau‐PET predict prospective longitudinal decline in specific cognitive domains in early symptomatic AD.MethodsSeventy‐nine amyloid‐positive participants with a clinical diagnosis of mild cognitive impairment (MCI, n=47) or AD dementia (n=32) underwent a 18Flortaucipir PET (80‐100 minutes after injection), structural MRI, and neuropsychological testing as part of the AVID A05 study (Table 1). Cognitive assessment was repeated after 9 and 18 months. Single‐test annualized w‐scores (age‐corrected z‐scores) at each time point were calculated against 52 controls (age=67.5±10.3) and combined in composite scores for episodic memory, semantic memory, executive function, language, and visuospatial domains. Latent growth curve models were applied to longitudinal composite scores to estimate the rate of annual decline (slope) in each participant. Standardized uptake value ratio (SUVR) images were created using inferior cerebellar gray matter as the reference region. Voxelwise regression analyses were used to identify patterns of baseline tau‐PET associated with longitudinal changes in each cognitive domain. Regression analyses were repeated using cortical regional baseline SUVR values, extracted using FreeSurfer, as predictors of subsequent cognitive decline.ResultsPatients significantly declined in all domains (Figure 1). Differential FTP‐PET patterns showed significant negative associations with domain‐specific annual rates of decline (r≤‐0.3, p<0.001; r≤‐0.5, pFWE<0.05 at voxel level, Figure 2). Specifically, higher tau‐PET SUVR in temporo‐parietal regions was predictive of faster decline in episodic memory, tracer retention in the left anterior temporal lobe related to worse semantic memory, while a more extensive and asymmetric tau‐PET pattern in (L>R) fronto‐temporal regions and (R>L) fronto‐parietal regions related to a faster decline in language and visuospatial domains, respectively. Executive decline showed small inter‐individual variability. Region‐based analyses highlighted similar tau‐PET patterns as predictive of domain‐specific decline (pFDR<0.05, Figure 3).ConclusionAt a group level, differential regional patterns of tau are associated with domain‐specific cognitive decline in MCI and early AD dementia. Tau PET may be a useful precision medicine tool for predicting patient‐specific trajectories in early symptomatic AD.