Normalized brain volume and white matter hyperintensities as determinants of cerebral blood flow in Alzheimer’s disease

Purpose: Patients with Alzheimer’s disease (AD) have a lower cerebral blood flow (CBF) compared to the general elderly population. It is still not fully understood whether this decreased CBF reflects neurodegeneration, or rather is the consequence of comorbid cerebral small vessel disease (SVD). We aimed to investigate the independent associations of normalized brain volume (NBV) and white matter hyperintensity (WMH) volume with CBF. Methods: We included 129 patients with AD (age 66±7 years, 53%female) and 81 controls (age 65±6years, 41%female). CBF was measured with pseudo-continuous arterial spin labelling (PCASL) at 3T for whole brain and in partial volume corrected (PVC) cortical and white matter maps. We used linear regression analysis, corrected for age and sex, to investigate independent associations for NBV and WMH volume with CBF. Results: In AD patients, smaller NBV was associated with lower whole brain (Stβ:0.28;p<0.01), cortical (Stβ:0.27;p<0.01) and white matter CBF (Stβ:0.18;p<0.05). In addition, larger WMH volume in AD patients was also associated with lower whole brain (Stβ:-0.21;p<0.05) and cortical CBF (Stβ:-0.23;p<0.05). In controls, NBV was not associated with CBF, but larger WMH volume tended to be associated with lower whole brain and cortical CBF when NBV and WMH were simultaneously entered in the model (respectively Stβ:-0.24 and Stβ:-0.25; both p=0.06). Conclusion: Our results indicate that in AD, lower CBF reflects the combined disease burden of both neurodegeneration and SVD. Both processes are assumed to contribute to AD and CBF as measured using PCASL may be a final common pathway.