18F-Flortaucipir PET Associations with Cerebrospinal Fluid, Cognition, and Neuroimaging in Mild Cognitive Impairment due to Alzheimer's Disease.

BACKGROUND

Tau positron emission tomography (PET) imaging is used in research, but its relation to cerebrospinal fluid (CSF) tau and other Alzheimer's disease (AD)-related clinical measures is unclear in mild cognitive impairment with AD biomarkers (MCI-AD).

OBJECTIVE

To determine associations between 18F-flortaucipir PET and CSF AD biomarkers, cognitive functioning, and neuroimaging measures in MCI-AD.

METHODS

In 29 participants 50 years or older with MCI-AD, 18F-flortaucipir PET, CSF total tau (T-tau), phosphorylated tau181p (P-tau), amyloid-β (Aβ), structural MRI, and neuropsychological testing were collected as baseline assessments of an ongoing clinical trial. 11C-Pittsburgh compound B PET was simultaneously conducted in 20 participants. Associations between 18F-flortaucipir PET and these measures were assessed by multiple linear regression adjusted for potential confounders and using global, lobar, and voxel-wise standardized uptake value ratio (SUVr).

RESULTS

Whole brain 18F-flortaucipir SUVr was significantly associated with CSF T-tau (r = 0.68, p < 0.001) and P-tau (r = 0.42, p = 0.04) after adjusting for age, sex, race, and education, with strongest associations in the temporal region (T-tau: r = 0.69, p < 0.001; P-tau: r = 0.49, p = 0.02). Voxel-wise analysis confirmed these regional associations. 18F-flortaucipir PET was also associated with CSF Aβ (r = -0.45, p = 0.03), episodic memory (r = -0.61, p = 0.001), visuospatial working memory (r = -0.46, p = 0.02), and brain cortical thickness (r = -0.44, p = 0.03) but not hippocampal volume. In the amyloid PET subset, although 11C-PiB PET associated strongly with 18F-flortaucipir (r = 0.79, p≤0.001), associations were stronger between 11C-PiB and key outcomes, compared to 18F-flortaucipir.

CONCLUSION

18F-flortaucipir PET is moderately associated with CSF AD biomarkers and other AD-related phenotypes. The associations in this MCI-AD sample are stronger than previously described in other populations.