Date of Award


Level of Access Assigned by Author

Open-Access Dissertation

Degree Name

Doctor of Philosophy (PhD)




Merrill F. Elias

Second Committee Member

Michael A. Robbins

Third Committee Member

Adam Davey


Although the associations among diabetes mellitus, cognitive functioning and arterial stiffness have been explored previously, the degree to which arterial stiffness is responsible for the association between diabetes and cognitive function has not been examined. The primary aim of the current investigations is to examine the extent to which arterial stiffness mediates the association between diabetes and cognitive function, as well as the extent to which this indirect effect is modified by age and APOE genotype. The sample included 590 participants (age 23-94, 62% women, 12% African- American) from the seventh wave of the Maine-Syracuse Longitudinal Study. Individuals with history of stroke, probable dementia, and PWV error of estimate >0.20 were excluded. Diabetes was defined as elevated glucose or treatment. Pulse wave velocity was used to as an indirect measure of arterial stiffness. Multiple statistical methods were used to examine the association between diabetes and cognitive function, as well as between PWV and cognitive function. Then, path analysis was used to examine the direct and indirect (through PWV) associations between diabetes and cognitive function. With adjustment for demographic and CVD risk variables, associations between diabetes and multiple measures of cognitive ability were observed for the APOE-ε4 carriers only. PWV was related to multiple cognitive measures, and this association was modified by age such that the lowest performance was observed in older individuals with elevated PWV. When diabetes, PWV and cognitive function were included together in the analysis of paths between variables, an indirect association between diabetes and cognitive function through PWV was observed, such that diabetes related to higher PWV, and lower cognitive function in older APOE-ε4 carriers. These findings may have important clinical implications with regard to attenuating the pronounced association between diabetes and cognitive function observed for persons who carry the APOE-ε4 allele. Accelerated arterial stiffness may possibly be treated by the same methods that are used to treat hypertension. Clinical trials are necessary to determine if modification of levels of PWV by drugs and other treatments will lead to an improvement in cognitive performance. Treatment specific to APOE genotype are also a possibility.