An examination of the association between hypertension, hypercholesterolemia and cognition in middle-aged and older Australian women

It is estimated that by 2051, 9.4% of the Australian population will be 80 years or older, with almost 70% of them being women (Australian Bureau of Statistics (ABS), 2008). The focus of aging research, therefore, is to discover ways to help this aging population maintain optimal health and cognitive functioning throughout old age. Cardiovascular disease (CVD) is a leading threat to the health and quality of life of Australian women (Australian Institute of Health and Welfare (AIHW), 2010a) and has also been associated with the development of cognitive impairment. As many CVD risk factors are modifiable through lifestyle changes and pharmacological interventions, there is enormous potential to improve the CVD risk profile of Australian women and consequently reduce the societal, economic and health implications of CVD, including cognitive impairment. The two most common CVD risk factors are hypertension and hypercholesterolemia, with more than half of Australians aged 25 years and over having one of these conditions (Dunstan et al., 2000). Both factors, particularly when presented at midlife, not only predispose one to the development of CVD but are also associated with increased neuropathology such as WMLs and AD-related neuropathology and subsequent cognitive impairment. However, most of the midlife studies have included participants with a wide age-range (55-88 years) which could have included participants with substantial neuropathology and probable dementia, and have assessed cognition much later in late-life (70-80 years old) that could over-estimate the BP- and cholesterol-cognition relationship. Whilst absolute BP and cholesterol levels are important predictor of cognitive functioning, overall BP and cholesterol health (e.g., pattern of fluctuation/variability) across midlife, which may be a proxy for overall BP and cholesterol control over time, could also provide additional information on the role of hypertension and hypercholesterolemia on cognition. Yet few, if any studies, have investigated this. With the exponential increase in the aging population and a disproportionate number of whom will be women, women-specific research on the BP- and cholesterol-cognition relationship has the potential to generate important and valuable findings that will aid in healthcare treatment and planning for this growing elderly population. This study, therefore, utilizes the wealth of vascular and cognitive data collected from the Women’s Healthy Ageing Project (WHAP) and seeks to investigate the relationship between hypertension and hypercholesterolemia on cognition in healthy women from midlife to late-life (56 - 67 years). Studies 1 and 2 assessed the associations between hypertension and cognition, while Studies 3 and 4 examined the associations between hypercholesterolemia and cognition. In all four studies, the present findings indicated that the timing of exposure is an important factor in determining the BP-cognition and cholesterol-cognition relationships. Findings from Studies 1 and 2 demonstrated that both higher absolute BP (in midlife and late-life) and mean BP levels across midlife, even at prehypertensive levels, are significant predictors of poorer late-life episodic memory. The opposite, however, is found for cholesterol-cognition relationship. Study 3 reported that that lower total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-C), and not high-density lipoprotein cholesterol (HDL-C), at midlife and late-life is associated with worse processing speed at late-life. The absence of an association between HDL-C and cognition could be due to the inherently high biological variance in cholesterol levels. Study 4 further examined the pattern of cholesterol variability over the decade of follow-up and reported that greater HDL-C variability across a decade is related to worse late-life episodic memory. There are limitations in this study. In particular, participants in this thesis research represent a high-functioning, healthier and relatively well-educated cohort compared to women in Melbourne of the same age range hence generalizability of current findings is limited. Nonetheless, findings from this thesis research have significant contributions to the paucity of women-specific aging studies and is one of the few studies to have extensively controlled for various vascular (e.g. anti-hypertensive and cholesterol-lowering treatment) and women-specific variables (e.g., hormone therapy (HT)) to elucidate independent effects of hypertension and hypercholesterolemia on cognition in women aged 56-67 years. Findings from the studies conducted in this thesis also highlight the importance of lifespan research, especially in diseases with a long prodrome. In particular, these findings have important clinical implications, particularly in the treatment of hypercholesterolemia in women, as aggressive cholesterol-lowering treatment in the elderly may prevent the development of CVD at the cost of cognitive impairment. Being one of the few women-specific aging studies, the ultimate goal of this study is to educate and promote awareness of CVD risk factors on cognitive well-being in aging women so as to help them achieve successful aging.