Search

Summary: Background: Neuroimaging studies often quantify tau burden in standardized brain regions to assess Alzheimer disease (AD) progression. However, this method ignores another key biological process in which tau spreads to additional brain regions. We have developed a metric for calculating the extent tau pathology has spread throughout the brain and evaluate the relationship between this metric and tau burden across early stages of AD. Methods: 445 cross-sectional participants (aged ≥ 50) who had MRI, amyloid PET, tau PET, and clinical testing were separated into disease-stage groups based on amyloid positivity and cognitive status (older cognitively normal control, preclinical AD, and symptomatic AD). Tau burden and tau spatial spread were calculated for all participants. Findings: We found both tau metrics significantly elevated across increasing disease stages (p

Introduction: Mid-life cardiovascular and late-life structural cerebrovascular pathology play a major role in accelerating cognitive decline in normal aging and dementia. Cerebral blood flow (CBF) may be a critical intermediate biomarker of future cognitive decline, however our understanding of normal CBF variability and its relation with mid-life cardiovascular and late-life structural cerebrovascular parameters is limited. The MRC National Survey of Health and Development neuroimaging sub-study ‘Insight 46’ provides a unique opportunity to study the effects of cardiovascular and cerebrovascular health on CBF in a cohort with a fixed chronological age. We explored associations of life-long cardiovascular parameters and WMH volume with ASL MRI CBF in this cognitively healthy population-based sample. Methods: 3D T1-weighted, FLAIR, and pseudo-continuous ASL (labeling duration = 1800ms; post-labelling delay = 1800ms) data (3T) were acquired in 295 participants (Table 1). Clinical data included systolic blood pressure (SBP), diastolic blood pressure (DBP), mean arterial pressure (MAP), pulse pressure (PP), and the Framingham Risk Score (FRS). MRI scans were processed with ExploreASL. Grey matter (GM), white matter (WM) and white matter hyperintensity (WMH) volume were segmented from the T1w and FLAIR images. ASL- derived partial volume-corrected CBF and the spatial coefficient of variation (sCoV) were obtained in whole-brain GM and WM. Linear regression models examined associations between life-long cardiovascular health (ages 43, 53, 60-64, 69, and 69-71 years), ASL metrics (at 69-71 years), and WMH load (at 69-71 years). Models were corrected for sex, and sex interactions were tested if applicable. Results: While mid-life cardiovascular parameters were associated with late-life sCoV and CBF, the strongest associations were seen at 69-71 years. At this time point, higher SBP and MAP were associated with lower GM CBF in men (1A-B, β=-0.16,-0.28) and relatively stable GM CBF in women (1A-B, β=0.02,-0.02); higher DBP was associated with lower GM CBF (β=-0.18). Higher WMH volume was related to higher GM and WM CBF (2A-B, β=2.04,1.45), and lower GM and WM sCoV (2C-D, β=-0.04,0.05). Discussion: These sex-dependent associations encourage further investigation into the potential mediatory role of CBF between mid-life cardiovascular and late-life structural decline of cerebrovascular health, leading to cognitivexxxxx