Premium
Relationships between cerebrovascular health and tau PET uptake are associated with global cognition
Author(s) -
Albrecht Daniel,
Isenberg Lisette,
Stradford Joy,
Monreal Teresa,
Sagare Abhay P,
Pachicano Maricarmen,
Toga Arthur W.,
Zlokovic Berislav V,
Chui Helena C,
Joe Elizabeth B,
Schneider Lon,
Conti Peter,
Jann Kay,
Pa Judy
Publication year - 2020
Publication title -
alzheimer's and dementia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 6.713
H-Index - 118
eISSN - 1552-5279
pISSN - 1552-5260
DOI - 10.1002/alz.045326
Subject(s) - cerebral blood flow , montreal cognitive assessment , cognition , psychology , mediation , medicine , cohort , oncology , neuroscience , cardiology , cognitive impairment , political science , law
Background Brain accumulation of tau and cerebrovascular dysfunction are both important contributors to AD pathogenesis, but associations between vascular health and tau levels, and their effects on clinical outcome, are poorly understood. We investigated these associations in a cross‐sectional study, by performing comparisons between cerebral blood flow (CBF), measured with ASL perfusion MRI, and tau PET uptake, measured with [ 18 F]flortaucipir (FTP). In a subgroup, we assessed relationships between tau uptake and a CSF marker of vascular health known to be associated with impaired cognition, soluble platelet‐derived growth factor beta (sPDGFR‐β). Method We conducted discovery and replication analyses using data from USC (n=68) and ADNI (n=136), respectively. Voxelwise analyses assessed relationships between CBF and FTP standardized uptake value ratio (SUVR), the results of which were used to mask the replication analysis. Secondary analyses were performed on the replication dataset with a gray matter mask. Analyses were corrected for age, sex, gray matter volume, and diagnosis (when appropriate), with voxelwise and cluster‐level thresholds of p<0.001 and p<0.05, respectively. General linear models were used to determine if CBF‐FTP relationships differed between diagnostic groups, as well as between high and low performance on the Montreal Cognitive Assessment (MoCA), a measure of global cognition. Mediation models assessed the relationship between tau, sPDGFR‐β, and cognition. Result In the discovery cohort, we observed negative CBF‐FTP correlations mainly in lateral and inferior temporal regions, that were largely replicated in the ADNI cohort. Secondary analyses demonstrated that early negative CBF‐FTP correlations increased in spatial extent and strength of correlation with increased disease severity. Stronger negative CBF‐FTP correlations were observed in participants with more advanced diagnoses and in those with poorer global cognitive performance. sPDGFR‐β was a significant mediator of the relationship between inferior temporal tau uptake and MoCA. Conclusion Our results provide evidence that associations between the cerebrovascular system and tau binding may affect cognition across the AD spectrum. Importantly, the sPDGFR‐β analysis suggests that vascular dysfunction may contribute to cognitive impairment via elevations in tau, potentially caused by reduced tau clearance. Future, longitudinal studies are needed to explore the complex temporal relationship between tau deposition and vascular health.