Cerebral Artery Pulsatility is Associated with Cognitive Impairment and Predicts Dementia in Individuals with Subjective Memory Decline or Mild Cognitive Impairment

The concept that excess pulsation in cerebral arteries might be involved at the early stage of dementia is based on the results of studies on aorta stiffness. In these studies, aorta stiffness is cross-sectionally associated with cognitive impairment and longitudinally related to cognitive decline in non-demented subjects. However, a direct measure of cerebral artery pulsatility is absent in the literature. We aimed to investigate the associations between cerebral artery pulsatility and (1) different cognitive-domains and (2) conversion to dementia in non-demented individuals at the prodromal-stage of Alzheimer's disease (AD). Non-demented individuals with subjective memory decline or mild cognitive impairment were included. Neuropsychological tests at baseline and cognitive status at 6 years were evaluated. Cerebral pulsatility was assessed in the middle cerebral artery (MCA) and posterior cerebral artery by transcranial color-coded sonography. Multivariate-analyses of 79 subjects with robust acoustic windows showed that increased pulsatility in cerebral arteries was significantly associated with impairment in corresponding cognitive domains. Analyses in 54 subjects who completed 6-year follow up revealed that high left MCA pulsation (pulsatility index >= 1.1) independently predicted conversion to AD with an odds-ratio of 11.2. Our results demonstrate the spatio-temporal relationship between increased cerebral artery pulsation and cognitive impairment and suggest that increased cerebrovascular pulsation might be involved in the early pathogenesis of AD. Cerebrovascular pulsation may be a therapeutic target to prevent/delay AD onset. Future studies with other AD biomarkers and animal/cell models of increased vascular-pulsation are needed to elucidate the mechanisms by which cerebrovascular pulsatile injury initiates or precipitates neurodegeneration in AD.