The repeated occurrence of stressful situations, leading to ‘allostatic load’, are said to result in cumulative age-dependent illness [1]. Disease trajectories, such as towards hypertension and stroke are said to be consequences of allostatic load [2]. Lifetime hypertension predicts brain structure 28 years later [3]. Multi-measure cardiovascular and stroke risk scores, such as the Framingham Risk scores [4] predict subsequent cognitive decline, grey matter volume reduction and white matter changes [5]. The aims of the present analysis are two-fold: 1) to establish whether there is an association between the Framingham Stroke Risk Profile (FSRP) in mid-life across five phases (P) and reduced structural brain integrity and 2) to establish whether the predicted effects on brain structure reduction in older age are the same 5 (P9), 10 (P7), 15 (P5) and 22 (P3) years before as at the time of the scan (P11) [6].MRI data from 405 participants of the Whitehall II imaging sub-study were analysed (age 69.6±5.2 years, range 60 to 83, M:F=321:84). T1 and dMRI scans were acquired as part of the imaging protocol previously described [7]. Voxelwise GLM analysis was performed using Randomise in FSL tools [8] to assess the correlation between grey matter density (GMD) reduction and FSRP at each phase using voxel based morphometry (FSL-VBM) and fractional anisotropy (FA) and FSRP at each phase using tract-based spatial statistics (TBSS). In a second analysis, correlations with FSRP at P11 including P9 - P3 in turn as confound regressors were run using both FSL-VBM and TBSS. Correcting for multiple comparisons, the significance threshold was set at p < .05, using threshold-free cluster enhancement (TFCE; [9]). Lastly, grey matter intensity values were extracted from the grey matter mask of the third stage of FSL-VBM, a combined mask of the precuneus and posterior-singulate gyrus (P+PCG) and the left and right hippocampi separately. Grey matter intensity values of each mask were correlated with FSRP at each phase, as well as with FSRP at P11 controlling for P9 – P3. FA values were extracted from the frontal white matter tracts and correlated with FSRP at each phase, as well as with FSRP at P11 controlling for P9 – P3.FSL-VBM analysis: Significant widespread correlations were found between GMD reduction and FSRP at P11 – P3. No significant correlation was found between GMD reduction and FSRP at P11, controlling for P9. Significant correlations were found between GMD reduction and FSRP at P11, controlling for P7, P5 and P3. The spread of correlations was reduced in size, localised to the medial temporal lobes. TBSS analysis: Significant widespread correlations were found between FA reduction and FSRP at P11 – P5. Significant widespread correlations were found between FA reduction and FSRP at P11, controlling for P9 – P3. Both FSL-VBM and TBSS findings were supported by correlations between extracted grey matter intensity / FA values respectively, and FSRP at each phase, as well as with FSRP at P11 controlling for P9 – P3. The above findings suggest that 1) a significant association between FSRP and GMD reduction is present in mid-life as early as 22 years before the time of the scan. A significant association between FSRP and FA reduction is also present in mid-life, 15 years before the time of the scan. 2) The associations between FSRP and GMD reduction are significantly different in three midlife phases compared to at the time of the scan in older life. The lack of significant correlation between GMD reduction and FSRP at P11 controlling for P9 suggests a lack of additional GMD reduction predicted by FSRP in older age compared to 5 years before the scan. Additional GMD reduction is predicted by FSRP in older age compared to 10 years before the scan, in the medial temporal lobes. This additional association in the medial temporal lobes remains present in relation to FSRP 15 and 22 years before the scan, due to the plasticity of these areas. In contrast, FSRP in older age does not predict additional GMD reduction in posterior and cortical areas such as the P+PCG. 3) The associations between FSRP and FA reduction are significantly different in four phases compared to at the time of the scan in older age. These associations become more widespread the further away FSRP is from the time of the scan in older age.These findings highlight the importance of reducing risk factors that contribute to FSRP in midlife, as well as the differential effect of FSRP on different parts (including grey and white matter) of the brain.