Longitudinal and cross-sectional structural magnetic resonance imaging correlates of AV-1451 uptake

Abstract

We examined the relationship between in vivo estimates of tau deposition as measured by F-AV-1451 tau positron emission tomography imaging and cross-sectional cortical thickness, as well as rates of antecedent cortical thinning measured from magnetic resonance imaging in individuals with and without evidence of cerebral amyloid in 63 participants from the Alzheimer's Disease Neuroimaging Initiative study, including 32 cognitively normal individuals (mean age 74 years), 27 patients with mild cognitive impairment (mean age 76.8 years), and 4 patients diagnosed with Alzheimer's disease (mean age 80 years). We hypothesized that structural measures would correlate withF-AV-1451 in a spatially local manner and that this correlation would be stronger for longitudinal compared to cross-sectional measures of cortical thickness and in those with cerebral amyloid versus those without. Cross-sectional and longitudinal estimates of voxelwise atrophy were made from whole brain maps of cortical thickness and rates of thickness change. In amyloid-β-positive individuals, the correlation of voxelwise atrophy across the whole brain with a summary measure of medial temporal lobe (MTL) F-AV-1451 uptake demonstrated strong local correlations in the MTL with longitudinal atrophy that was weaker in cross-sectional analysis. Similar effects were seen in correlations between 31 bilateral cortical regions of interest. In addition, several nonlocal correlations between atrophy andF-AV-1451 uptake were observed, including association between MTL atrophy and F-AV-1451 uptake in parietal lobe regions of interest such as the precuneus. Amyloid-β-negative individuals only showed weaker correlations in data uncorrected for multiple comparisons. While these data replicate previous reports of associations betweenF-AV-1451 uptake and cross-sectional structural measures, the current results demonstrate a strong relationship with longitudinal measures of atrophy. These data support the notion that in vivo measures of tau pathology are tightly linked to the rate of neurodegenerative change.

Association of deposition of tau and amyloid‐β proteins with structural connectivity changes in cognitively normal older adults and Alzheimer’s disease spectrum patients

“…Meanwhile, the amyloid‐positive AD‐spectrum group showed decreased connectivity, which is consistent with previous studies that MCI/AD in general has often been associated with decreased structural connectivity (Mielke et al, ; Nowrangi et al, ; Wisse et al, ) and atrophy (Das et al, ; Maass et al, ; Xia et al, ). Aβ is hypothesized to increase tau deposition and to accelerate the spread of hyperphosphorylated tau beyond the collateral sulcus into the neocortex, via transsynaptic spread across neural networks.…”

Applications of amyloid, tau, and neuroinflammation PET imaging to Alzheimer's disease and mild cognitive impairment

“…Interestingly, patients with a high degree of retention in the entorhinal cortex displayed particularly poor memory functioning (Whitwell et al, 2018). A recent study also links tau burden quantified by [ 18 F]AV-1451 to neurodegeneration, specifically longitudinal brain atrophy (Das et al, 2018). Other neurodegenerative pathology shows unique profiles of tau aggregation as detected by this tracer.…”

Tau pathology in cognitively normal older adults

“…Lower hippocampal volume has also been associated with greater tau radiotracer retention in the hippocampus [8,10]. Longitudinal studies including individuals ranging from CN to demented have further found that higher baseline tau tracer retention is associated with greater rates of brain volume loss [11,12] and global cognitive decline [13–15].…”