Background: There is great interest in interplay between cerebrovascular disease (CVD) and amyloid in mediating cognitive decline. Vascular disease risk factors increase risk for dementia, however whether this is synergistic or additive to concurrent AD-pathology is unclear.
      Methods: 287 participants from the Australian Imaging, Biomarkers and Lifestyle Study of Ageing, ranging from normal cognition through MCI to AD dementia, assessed four times over 54 months with 11C-PiB PET, 3T-MRI and neuropsychology assessment. 174 also had SWI MRI for microbleeds and 80 had carotid intima-media thickness (CIMT) measurement. Linear mixed models regression was used to compare outcome (cognitive score, PET SUVR, atrophy) between groups with and without significant PiB and CVD burden over time. Subanalyses also tested whether greater carotid intima-media thickness (CIMT) or lobar microbleeds (LMB) influenced change in PiB.
      Results: 21/151 NC and 24/32 MCI had declined (e.g. NC-MCI, MCI-AD) by 54 months. A similar proportion of PiB+CVD+ and PiB+CVD- NC declined at 54 months (25.0% vs 26.7%) compared with PiB-CVD+ (14.3%) and PiB-CVD- (9.1%) (X 2 =6.3, p=0.01). For MCI, 100% (4/4) of PiB+CVD+ MCI vs 69.2% of PiB+CVD- declined, 2/2 PiB-CVD+ and 1/10 PiB-CD- (X 2 =15.3, p=0.002). Both PiB+ and CVD+ were associated with cognitive decline in univariate models, however after correcting for age, E4, gender and education, PiB+ remained significant, whereas CVD+ was not. In mixed models analyses adjusted for age, education and E4 status, PiB and CVD were additive, but not interactive, in influencing longitudinal change in episodic memory (CVLT-long delay) and global cognitive function (CDR-SOB). There was no significant difference seen in the accumulation of PiB over time between CVD+/-, nor in subanalyses by CIMT or lobar microbleeds.
      Conclusions: In this sample, PiB and CVD were additive but not interactive processes in mediating cognitive decline, and no association was seen between markers of vascular pathology and longitudinal PiB accumulation.