Melbourne School of Psychological Sciences - Theses
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ItemThe effect of vascular risk factors in dementia of the Alzheimer's type( 2016)The influence of vascular risk factors on Alzheimer’s disease and its clinical presentation is an area of intense scientific debate. There is now growing evidence to suggest that the presence of vascular risk factors in early-stage Alzheimer’s disease might accelerate its clinical presentation. Previous studies have also demonstrated that clinically healthy individuals with vascular risk factors perform below expectations on cognitive assessment. Further, the burden of vascular risk factors might be a predictor of future cognitive decline. However, the relationship between vascular risk factors and cognitive deterioration in healthy older adults has not been clearly established. The aim of this study was to investigate the relationship between vascular risk factors and cognitive function in a large cohort of 768 cognitively healthy older individuals drawn from the Australian Imaging, Biomarkers and Lifestyle (AIBL) Study of Ageing. This thesis addresses four main questions: (1) is there a difference in cognitive performance between individuals with and without vascular risk factors?, (2) does the presence of vascular risk factors affect the rate of cognitive change? (3) does the number of vascular risk factors influence cognition? and (4) does the presence of vascular risk factors increase the likelihood of developing Mild Cognitive Impairment? Participants were aged between 60–95 years, (M= 69.9 ± 6.9). All participants underwent a comprehensive baseline assessment and three additional serial assessments were repeated at 18-month intervals over a 54-month period. By the end of the study period, 172 individuals had withdrawn from the cohort. Of the remaining 596 participants, 43 had attracted a classification of Mild Cognitive Impairment. The sample was divided into subgroups of those with and without vascular risk factors. Participants in the vascular risk factors sub-group had at least one of the following risk factors: (1) hypertension, (2) diabetes, (3) dyslipidaemia, (4) Body Mass Index > 30 kg/m², (5) chronic kidney disease, (6) smoking history of more than 20 cigarettes per day for more than one year, and (7) elevated homocysteine levels (males>16.2 μmol/L; females>13.6 μmol/L). This thesis comprises a series of analyses. For the first analysis, demographic characteristics of individuals with and without vascular risk factors was compared. The data suggested that vascular risk factors were associated with older age (F (1, 712) = 8.1, p = 0.005), lower level of education (χ2 (1, n =711) = 7.8, p = 0.005) and apolipoprotein E ε4 carriage (χ2 (1, n = 714) =6.9, p = 0.009). In the second analysis, a statistically significant difference in cognitive performance between individuals with and without vascular risk factors was identified (F (4, 669) = 4.28, p = 0.002; partial eta square = 0.03). The results revealed that participants with vascular risk factors demonstrated poorer performance on variables that assessed visual cognition and executive functions than participants without vascular risk factors. In the third analysis, from a longitudinal perspective, five specific neuropsychological tests were subjected to a linear mixed model adjusted for age and apolipoprotein E ε4 carriage. The presence of vascular risk factors was associated with increased rates of cognitive decline on measures of verbal fluency (F (2, 1096.8) = 3.03, p < 0.05) and visuospatial skills (F (1204.6, 1) = 1.055; p < 0.05). The relationship between vascular risk factors and cognitive decline became more evident in the fourth analysis when the neuropsychological test battery was reduced into cognitive composite measures. Participants with vascular risk factors showed significantly greater decline on measures of verbal (F (624.016, 1) = 7.2; p = 0.01) and visual (F (1775.533, 1) = 6.89; p = 0.01) memory, as well as on visuospatial skills (F (1204.6, 1) = 1.055; p = 0.03) and executive functions (F (1821.035, 1) = 4.48; p = 0.03). No difference was found in the language composite measure. In the fifth analysis, higher vascular risk factor burden was associated with increased rates of cognitive decline, suggesting the presence of a dose-response relationship. In individuals with three or more vascular risk factors, a higher magnitude of decline on tasks that measure executive functions (Cohen's d = 0.35), visuospatial skills (Cohen's d = 0.35) and visual memory (Cohen's d = 0.47) was identified. No dose-response relationship was found in either the language or verbal memory cognitive domains. The sixth analysis focused on the group of participants who attracted a diagnosis of MCI over the 54 months. The data showed that there was a significant difference in the vascular risk factor burden distribution between individuals who remain cognitively stable and those who transition to Mild Cognitive Impairment (X² (2) = 44.88, p < 0.001), with greater risk factor burden observed in the latter. The interaction effect between clinical classification and presence/absence of vascular risk factors on the cognitive composite factors was further investigated. The only cognitive variable that showed a statistically significant difference was the visuospatial skill composite (1, 513) = 5.52; p = 0.019; partial eta square = 0.011). Finally, the analysis showed that vascular risk factors increased the likelihood of developing Mild Cognitive Impairment by 39%. In conclusion, the data suggest that vascular risk factors confer a degree of cognitive vulnerability on cognitively healthy older adults. This effect appears to be selective, impacting executive functions and visuospatial cognition but not language and verbal memory. Executive functions and visuospatial cognition are complex cognitive domains and share extensive distributed networks, which may increase their susceptibility to vascular risk factors over time. Based on the overall findings of this research, we propose that vascular risk factors – in combination with genetic and demographic factors – contribute to a reduction of brain reserve, precipitating an earlier onset of cognitive decline in the transition to Mild Cognitive Impairment. This implies that individuals who suffer from several risk factors may have less brain reserve and may therefore be more susceptible to developing dementia. Vascular risk factors are preventable for at least 95% of people with relatively simple changes in diet and lifestyle. The findings from this thesis contribute to a developing literature suggesting that decreases in vascular risk may reduce susceptibility for dementia and cognitive decline in later life.