Brain amyloid in later life increases with number of midlife vascular risk factors
Association Between Midlife Vascular Risk Factors and Estimated Brain Amyloid Deposition
Gottesman RF, Schneider ALC, Zhou Y, et al. - JAMA 2017;317(14):1443-1450Background
It becomes more evident that vascular risk factors are involved in the development of Alzheimer disease (AD) [1-4]. However, whether these risk factors can directly cause enhanced neurodegeneration that is specifically associated with AD, such as through increasing amyloid deposition, or lead to other cerebral changes, is unknown. Similarly, for the APOE Ɛ4 gene, which is known as a genetic risk factor for AD, though its role in the association between AD and vascular disease is unclear [5].
Brain amyloid can be measured using imaging biomarkers. In current study, the associations between vascular risk factors, APOE genotype and brain amyloid deposition were evaluated using data from participants of the ARIC study (Atherosclerosis Risk in Communities) of whom vascular risk factors (BMI ≥30/obesity, current smoking, hypertension, diabetes, total cholesterol ≥200 mg/dL) were collected for over 25 years and brain amyloid position PET imaging obtained in late life (n=322).
Main results
- 50.9% had an elevated (above median) amyloid standardized uptake value ratio (SUVR).
- Corrected for age, sex, race, education level, APOE Ɛ4 genotype and vascular risk factors, elevated BMI was the only midlife vascular risk factor that was statistically significantly associated with elevated amyloid (OR 2.06, 95% CI 1.16-3.65). None of the late life vascular risk factors were associated with elevated amyloid.
- More vascular risk factors in midlife, but not late life, was associated with elevated brain amyloid as 31% of individuals with elevated amyloid in late life had 0 vascular risk factors in midlife, whereas 61% had at least 2 vascular risk factors in midlife.
- Each additional midlife vascular risk factor associated with an OR of 1.41 for elevated amyloid at late life (95% CI 1.09-1.83).
- Although odds increased with increasing number of risk factors, odds decreased with age.
- The association between number of risk factors and elevated odds of amyloid was only observed to be significant in white and not in black individuals (OR 1.66, 95% CI 1.15-2.39 and OR 1.26, 95% CI 0.85-1.88, respectively). However, P interaction of race by number of risk factors was not significant (P=0.42).
- This was also observed for men versus women (OR 6.77, 95% CI 2.37-19.35 and OR 1.71, 95% CI 0.66-4.45, respectively, P interaction = 0.36).
- Individual vascular risk factors did not interact with APOE status.
- Odds of elevated amyloid in participants with elevated BMI were statistically similar regardless of APOE status (OR 2.48, 95% CI 1.26-4.88 for APOE Ɛ4 carriers and OR 1.11, 95% CI 0.85-1.44 for noncarriers, P interaction = 0.50).
- When analysed visually, continuous SUVR was associated with the number of APOE Ɛ4 alleles in the setting of increasing systolic blood pressure, BMI or midlife 10-yrs stroke risk score.
- Stratification by APOE status showed absence of interaction between APOE and the number of risk factors.
- Increasing number of late life risk factors was not associated with elevated amyloid deposition, regardless of APOE status (OR overall cohort, 1.02, 95% CI 0.43-2.43 and 1.66, 95% CI 0.75-3.69, for 1 and ≥2 risk factors respectively).
Conclusion
An increased number of midlife, but not late life vascular risk factors was associated with elevated brain amyloid in later life. The relationships between vascular risk factors and brain amyloid did not differ by race, nor by status of the APOE allele.