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MIDLIFE VASCULAR RISK, APOLIPOPROTEIN E-E4, AND AMYLOID STATUS 20 YEARS LATER: RESULTS FROM THE WOMEN’S HEALTHY AGEING PROJECT

      Background: There are conflicting reports linking vascular risk factors and Alzheimer's disease biomarkers and histopathology. Timing of exposure to risk factors may be critical in mediating their association. However there is little literature to date examining mid-life risk measurements with later-life disease-specific biomarkers such as amyloid PET imaging.
      Methods: 125 participants from the Women's Healthy Ageing Project, a longitudinal study of Australian women, with vascular risk measurements in 1992 and cognitive assessment and 18F-Florbetaben (FBB) PET imaging in 2012. FBB PET Standardized Uptake Value Ratio (normalized to the cerebellar cortex [SUVR]), and episodic memory measured by CVLT-long delay score, were compared by tertile of midlife PROCAM and Framingham Coronary Risk Scores. Groups were compared using ANOVA and linear regression models were performed including Risk Score tertile, age, education, apolipoprotein E- e 4 status, and e 4 x Risk Tertile.
      Results: Mean age was 49.9 ± 2.4 years at vascular risk assessment and 68.8 ± 2.3y at time of PET scan/CVLT. Participants in the highest PROCAM tertile had significantly higher late-life mean FBB SUVR than those in intermediate (p<0.04) or low tertiles (p<0.03), and poorer mean CVLT performance (10.5 ± 4.6 words vs 12.2 ± 3.0 words, p<0.02). Similar, though non-significant trends were also seen with midlife FCRP and late-life SUVR and CVLT. Midlife PROCAM tertile, e 4 status and e 4 x PROCAM were each significantly associated with late-life FBB burden, correcting for age and education. Age, years of education, and PROCAM tertile were independently associated with later-life CVLT-LD performance. In addition, the interaction between E4 status and PROCAM was significantly associated with CVLT-LD score, such that e 4+ with high PROCAM risk score performed much worse than e 4 non-carriers or low-risk PROCAM tertiles. Of component parts of the PROCAM, only LDL-cholesterol was associated with late-life SUVR in univariate analyses. This was largely attenuated when e 4 status was added to the model.
      Conclusions: Mid-life vascular risk factors are associated with both amyloid burden, assessed by Florbetaben PET, and poorer episodic memory function 20 years later. The presence of e 4 interacted to increase this association.