Obesity, excessive weight gain at midlife may take toll on cognition at later life

Both obesity and excessive weight gain at midlife bears a heightened risk of cognitive impairment at old age, according to a study. Conversely, excessive weight loss is not associated with a risk increase, although it may serve as an early marker of a “long and insidious process of cognitive decline.”

“Since obesity at midlife has been recognized as a potentially modifiable risk factor of dementia, reducing weight may intuitively seem to be a possible strategy that may protect against cognitive decline with ageing, and this could be mediated either through direct effects or through improvement in other metabolic factors implicated in pathogenesis of cognitive impairment,” the investigators pointed out. [Lancet 2017;390:2673-2734; Neurosci Biobehav Rev 2017;72:87-94]

In contrast, some studies have linked weight loss to worsening of cognition with ageing. Such phenomenon, described as the obesity paradox, controverts the potential cognitive benefits of weight loss. [JAMA Neurol 2016;73:439-446; Int J Obes 2015;39:1383-1389; PLoS One 2017;12:e0185960; J Gerontol A Biol Sci Med Sci 2017;72:855-86; J Am Geriatr Soc 2017:65:511-519]

In the present study, the investigators looked at 14,691 participants from the Singapore Chinese Health Study. They evaluated the change in weight from that reported at baseline (mean age, 53.0 years) to that recorded at the first follow-up (mean age, 58.6 years) in relation to cognitive impairment, which was determined using the Singapore Modified Mini-Mental State Examination (SM-MMSE) at the third follow-up (mean age, 72.9 years).

The median SM-MMSE score of the population was 26, and 1,893 participants (12.9 percent) were found to have cognitive impairment based on education-specific SM-MMSE cutoffs. Logistic regression models revealed that the risk of cognitive impairment relative to participants who had normal weight (body mass index [BMI] 18.5–22.9 kg/m²) was significantly higher in those with obesity (BMI ≥27.5 kg/m²) at baseline (odds ratio [OR], 1.33, 95 percent confidence interval [CI], 1.12–1.58) at the first follow-up (OR, 1.30, 95 percent CI, 1.10–1.54) and at the third follow-up (OR, 1.26, 95 percent CI, 1.05–1.50). [J Alzheimers Dis 2020;doi:10.3233/JAD-191052]

On the other hand, compared with participants with <5-percent weight change, those who had ≥10-percent weight gain were more likely to have cognitive impairment in old age. The ORs were 1.20 in the group who had 5–9.9-percent weight loss, 1.53 in the group with ≥10-percent weight loss, 1.00 in the group with 5–9.9-percent weight gain, and 1.50 in the group with ≥10-percent weight gain.

“To our knowledge, our study is the largest ... so far about weight change and cognitive impairment in Asian populations, and our results suggest that the adverse impact of excess weight on cognition may emerge at lower values in Chinese, which in turn supports the WHO recommendation of lower BMI cutoffs in Asians,” according to the investigators. [Lancet 2004;363:157-163]

However, the findings should be carefully interpreted in light of several study limitations, including the failure to assess cognitive performance of the participants at enrolment, as well as the controversial role of MMSE as a stand-alone single administration test in the identification of individuals with cognitive impairment at risk of dementia.

“Future studies are needed to disentangle the mechanisms underlying the effects of weight change on cognition, and to define ethnic-specific safe boundaries of weight change at middle and late life,” they said.