Influence of tau PET, amyloid PET, and hippocampal volume on cognition in Alzheimer disease

Abstract

Objective: To examine the independent and interactive influences of neuroimaging biomarkers on retrospective cognitive decline.

Methods: A total of 152 middle-aged and older adult participants with at least 2 clinical and cognitive assessments, a Clinical Dementia Rating score of 0 or 0.5, and a flortaucipir (¹⁸F-AV-1451) tau PET scan, a florbetapir (¹⁸F-AV-45) amyloid PET scan, and a structural MRI scan were recruited from the Knight Alzheimer Disease Research Center at Washington University in St. Louis. Cognition was assessed with standard measures reflecting episodic memory, executive functioning, semantic fluency, and processing speed.

Results: Results from retrospective longitudinal analyses showed that each biomarker had a univariate association with the global cognitive composite; however, when each marker was analyzed in a single statistical model, only tau was a significant predictor of global cognitive decline. There was an interaction between tau and amyloid such that tau-related cognitive decline was worse in individuals with high amyloid. There was also an interaction with hippocampal volume indicating that individuals with high levels of all 3 pathologies exhibited the greatest declines in cognition. Additional analyses within each cognitive domain indicated that tau had the largest negative influence on tests of episodic memory and executive functioning.

Conclusions: Together, these results suggest that increasing levels of tau most consistently relate to declines in cognition preceding biomarker collection. These findings support models of Alzheimer disease (AD) staging that suggest that elevated β-amyloid alone may be insufficient to produce cognitive change in individuals at risk for AD and support the use of multiple biomarkers to stage AD progression.

Figure 1. Longitudinal relationship between tau PET and cognitive decline as a function of amyloid PET status using an SUVR threshold of 1.22

Amyloid negative: Clinical Dementia Rating (CDR) score of 0 (n = 106) and 0.5 (n = 5); and amyloid positive: CDR score of 0 (n = 30) and 0.5 (n = 11). SUVR = standardized uptake value ratio.

Figure 2. Longitudinal relationship among tau PET, amyloid PET, and hippocampal volume in predicting cognitive decline

Standardized uptake value ratios were set at 1.22 for amyloid PET and 1.25 for tau PET. Tau negative, amyloid negative: Clinical Dementia Rating (CDR) score of 0 (n = 77) and 0.5 (n = 4); tau negative, amyloid positive: CDR score of 0 (n = 15) and 0.5 (n = 2); tau positive, amyloid negative: CDR score of 0 (n = 29) and 0.5 (n = 1); and tau positive, amyloid positive: CDR score of 0 (n = 15) and 0.5 (n = 9).