Abstract

Many medical disorders often result from a combination of factors that ultimately contribute to the onset of illness. Alzheimer's disease (AD) is a case in point. Although age has long been a primary risk factor, it is now thought that cardiovascular disease and other risk factors such as obesity and elevated blood pressure (1, 2) can contribute to the onset and pathology of the disorder. Recently, various epidemiological studies, including large prospective cohorts of diverse populations have suggested a strong positive association between elevated blood pressure and cognitive impairment (3). Moreover, a number of studies also suggest that being overweight or obese are risk factors for AD, poor cognitive function or cognitive decline over time in healthy elderly populations (1, 2, 4), while others have indicated that weight loss or being underweight also has an effect on the risk of dementia (e.g. (5)). In a recent meta-analysis, a U-shaped pattern was confirmed (p=0.034 for the BMI category quadratic term), with pooled odds ratios (ORs) and 95% confidence intervals (CIs) for underweight, overweight and obesity compared with normal weight in relation to incident dementia of 1.36 (1.07, 1.73), 0.88 (0.60, 1.27) and 1.42 (0.93, 2.18), respectively. These data suggest that both extremes of the weight spectrum may increase the risk of developing dementia. It is still unclear, however, how adiposity and hypertension may interact to modulate cognitive functioning among older adults. The study by Sakakura et al. (6) attempts to address this issue. Based on a extensive data collected among a sample of 184 Japanese hypertensive subjects aged 61-94 half of whom were very elderly (≥80 years), the authors find that leanness (BMI 14.5-20.3) in hypertensive individuals is associated with poor overall performance on the Mini-Mental State Examination (MMSE) as well as impairment on the attention/calculation portion of the test, confirming the relationship between the low end of the weight spectrum and poor cognitive function. The relationship between leanness and poor MMSE performance was seen across the group as a whole (OR 2.54, 95%CI 1.13-5.73, P=0.02) as well as in very old individuals alone (OR 3.94, 95%CI 1.31-11.82, P=0.01). These data add to our understanding of the association between weight, hypertension, cognitive function and age by showing that the risk of cognitive impairment is higher in very old, low weight hypertensive individuals. In contrast, the study does not find that obesity in older hypertensive individuals is associated with poor cognitive function. This is surprising in view of previous studies demonstrating a link between obesity and increased risk for dementia, yet the authors raise a good point. It may be that age is the most critical factor when assessing the relationship between weight and cognitive function in hypertensives, and that risk at middle age may not be the same as risk at older age, especially very old age. To fully understand this relationship, a lifecourse approach is needed to uncover the dynamic processes associated with adiposity, cognitive change and age in hypertension.

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