In this analysis from the Kame Project, we report that the risk for AD was reduced with higher late-life BMI at baseline and that the risks of dementia and AD were reduced with a slower rate of BMI decline over a follow-up period of approximately 8 years. More importantly, the extent to which change in BMI was associated with dementia depended upon baseline BMI such that overweight or obese participants at baseline had a more pronounced reduction in risk with slower decline in BMI compared to normal or underweight participants. These findings suggest that late-life adiposity is associated with the risk of dementia, where high and slowly declining BMI reduce the risk; or conversely, that low or fast declining BMI may be preclinical indicators for dementia.
The risk for dementia is believed to develop across the lifespan as the pathologic hallmarks have been detected decades before its clinical presentation. Because of its long prodromal period, assessing the characteristics of a risk factor is time-dependent and the potential for reverse causality exists. Our finding of a reduced risk of AD with higher baseline BMI is suggestive of a protective effect of higher BMI in late life, similar to findings from the Kungsholmen Project6
and the Chicago Health and Aging Project.20
This is different from what has been shown in midlife, where overweight or obesity increased the risk of dementia and AD.8
Our findings are in accord with others who have shown weight loss in later life to be a risk factor for dementia1,2
and for weight loss to precede the diagnosis of dementia.3,4
Hence, it may be that a nonlinear association exists where higher adiposity in midlife increases the risk of dementia and its subtypes, and that pathophysiologic changes associated with dementia then lead to declines in adiposity in late life.5
Measures of central fat distribution, including WC and WHR, are known to increase the risk of coronary heart disease21
more than total body weight. Evidence suggests that central obesity in midlife23
and late life24
increases the risk of dementia and AD. Our findings do not support a link between WC or WHR in late life and dementia risk. These findings are partially in accord with those of the Northern Manhattan study where continuous WC was not associated with dementia, AD, or dementia associated with stroke. The same study did, however, find that the risk of dementia associated with stroke was increased for the largest WC quartile compared to the smallest WC quartile.7
Additional studies at both midlife and late life are needed to further elucidate whether central adiposity is associated with the risk for dementia and its subtypes.
The finding that overweight or obese participants had a reduced risk of dementia with slower decline in BMI compared to those who were normal or underweight may reflect a floor effect. Those who are normal or underweight at baseline have less weight to lose compared to those who are overweight or obese, which would lessen their rate of change in BMI over the course of the study. It may also be that those who were normal or underweight at the beginning of the study and were losing weight at a faster rate were lost to follow-up since this weight loss could affect overall health. Taken together, the results suggest that having a slow rate of a decline in weight if previously overweight or obese may reduce risk more than being overweight or obese alone in late life.
The use of BMI categories for Asian populations in our study resulted in a high number (39.6%) of obese (BMI >25) participants at baseline compared to the United States prevalence of 12% in the early 1990s.25
Using the Caucasian BMI cutpoints reduced this number to 5.0% for obese (BMI >30) with the remaining 3.1% underweight (BMI <18.5), 57.3% normal (BMI = 18.5–25), and 34.6% overweight (BMI = 25–30). Since 96% of the participants in the Kame Project were 100% Japanese,9
and twin studies have shown that genetic influences on BMI are substantial,26
we considered the Asian, rather than Caucasian, categories to be more appropriate for our sample. Furthermore, studies have shown that Asians in general have higher body fat, greater centralized distribution of body fat, and higher WHR than Caucasians with lower or similar BMIs, which highlights the importance of redefining the categories to assess health risks in our sample.17
Despite this descriptive difference, we believe that our main findings are generalizable beyond Japanese American or Asian populations since we used continuous measures of baseline BMI and change in BMI that were independent of BMI categories.
Several biologic processes may explain the association between high and slower decline in BMI and reduced risk of dementia. Higher weight in late life may offer protection by increasing insulin-growth factor I levels,27
increasing leptin hormone levels known to be involved in regulation of synaptic plasticity in the hippocampus,28
and increasing the production of estrogen,29
all of which have been shown to be associated with better cognitive performance.30,31
Slower decline in BMI over the course of the study may indicate that preclinical changes associated with dementia are not occurring. Brain areas that control weight (i.e., mesial temporal cortex)32
are affected during the preclinical dementia phase that may lead to weight loss. Weight loss may also result from predementia apathy,33
reduced olfactory function,34
difficulty in eating,35
or inadequate nutrition36
due to cognitive impairment.
There are both strengths and limitations of this study that should be acknowledged. The first strength is that the association between various measures of adiposity and incident dementia and two of its subtypes were examined. Also, the study included both community and institutionalized individuals, minimizing any selection bias that may result from including only those healthy enough to remain independent in the community. Finally, we adjusted for multiple variables that would likely confound any associations between adiposity and dementia.
Limitations of this study include the relatively short follow-up period, which increases the potential for reverse causality to explain the findings. Also, our sample was limited to Americans who were of Japanese ancestry and thus may limit the generalizability to other populations. We also assumed that height was constant throughout the study period even though studies have shown that women and men lose 0.2 to 0.3 cm per year between the ages of 70 and 90 years37
; however, any error introduced would likely nondifferentially overestimate the rate of decline in BMI and not bias the findings. It is also possible that using BMI as our measure of weight may have underestimated adiposity in the elderly who generally have less lean body mass,38
which would have attenuated our findings. Finally, we had insufficient power to detect a relationship between adiposity and VaD, but did find similar point estimates as dementia and AD. Others studies with more power have shown a stronger effect for VaD than AD,7
suggesting that adiposity may exert its influence on dementia with a vascular origin.