Midlife Weight Loss May Increase Mild Cognitive Impairment Risk

weight scale
weight scale
Research indicates that a loss of weight beginning in midlife and continuing into late life increases risk of MCI.

Weight loss beginning in midlife and progressing into late life may be associated with an increased risk for mild cognitive impairment (MCI), results from the Mayo Clinic Study of Aging indicate.  

According to the paper published in JAMA Neurology, about 5 to 15% of persons per year with MCI will progress to dementia. Identification of risk factors for MCI is essential for the development of preventative measures.

In order to investigate the predictive value of weight change, Rosebud O. Roberts, MB, ChB, of the Department of Neurology and Epidemiology at  Mayo Clinic, Rochester, and colleagues analyzed changes in weight and body mass index (BMI) in 1895 cognitively normal adults aged 70 years and older (50.3% men; mean age, 78.5 years). Participants were assessed for incident MCI at 15-month intervals from baseline.

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Overall, women were found to have more fluctuation in weight during the study period and a lower maximum BMI and weight compared to men, who had higher rates of diabetes, smoking, and coronary artery disease. During the mean 4.4 years of follow-up, MCI was identified in 524 participants. Those with MCI were more likely to have hypertension, diabetes, CAD, stroke, be (APOE) ε4 carriers, and older.

Mean weight change was greater in those who developed MCI than those who were cognitively normal (-2.0 vs -1.2 kg, P=0.006). Women with incident MCI had similar weight loss compared to those without incident MCI (-1.9 vs 1.5 kg, P=012), while men with incident MCI had greater weight loss than those without MCI   (-2.1 vs -1.0 kg, P=0.02).

After adjusting for (APOE) ε4 status, education, and sex, weight loss from midlife to late life was associated with an increased risk for MCI (HR 1.04, 95% CI: 1.02-1.06, P<0.001), with a loss of 5kg/decade corresponding to a 24% increase in risk (HR, 1.24).

Further, they found that a higher midlife maximum weight and a lower late-life weight were associated with an increased risk for MCI. The effect was greater in men than women and was significant for maximum midlife weight and MCI risk (P=0.02 for the interaction).

The authors offer several possible explanations for this association, including the “anorexia of aging” possibly related to metabolic, dietary, and hormone production changes, as well as apathy, depression, or impairment of smell and taste associated with some neurodegenerative disorders. Notably, the association between high midlife weight and MCI could be related to metabolic abnormalities and cerebrovascular disease associated with obesity, the authors hypothesize.


Alhurani RE, Vassilaki M, Aakre JA. Decline in Weight and Incident Mild Cognitive Impairment Mayo Clinic Study of Aging. JAMA Neurol. doi:10.1001/jamaneurol.2015.4756.