Greater Weight Loss Later in Life Is Associated with Increased Risk of Mild Cognitive Impairment

August 26, 2016
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By Makoto Ishii, MD, PhD
Assistant Professor of Neuroscience and Neurology, Feil Family Brain and Mind Research Institute, Department of Neurology, Weill Cornell Medical College

SYNOPSIS: A prospective study of patients aged 70 and older determined there is an association between increasing weight loss during aging from midlife to late-life and increased incidence of mild cognitive impairment.

SOURCE: Alhurani RE, Vassilaki M, Aakre JA, et al. Decline in weight and incident mild cognitive impairment: Mayo Clinic Study of Aging. JAMA Neurol 2016;73:439-446.

Alzheimer’s disease currently remains an incurable disease. Avenues for potential future treatments hinge on the identification of risk factors for manifestation and contraction. One of the potential early warning signs of Alzheimer’s is mild cognitive impairment (MCI). MCI often precedes dementia, as anywhere between 5% and 15% of MCI patients yearly develop dementia. Moreover, weight-loss prior to late-life has previously been linked to increased dementia risk, often preceding neurodegeneration. Despite this, it is not yet clear whether increased weight-loss over time is truly a warning sign of dementia and associated with increased risk for minor cognitive impairment.

To examine this potential link, the authors conducted an investigation drawing patients from the Mayo Clinic Study of Aging, an ongoing prospective study that began in 2004. Patients eligible for the study were between ages 70 and 89 at the outset of the study, were not diagnosed with dementia prior to the study, and needed to consent to follow-up evaluations at 15-month intervals. Furthermore, in order to be included in the study, patients needed to demonstrate normal cognition at both their baseline evaluation and one subsequent follow-up, as well as have height and weight information available. Every participant was administered the Clinical Dementia Rating Scale and a questionnaire regarding functional activity. Each also received comprehensive psychological and neurological evaluation. At every evaluation the patient’s body mass index was calculated; diagnoses of normal cognition, MCI and dementia were all made by consensus. Medical records enabled the researchers to determine the maximum height and weight at midlife. Medical records coupled with baseline testing allowed the researchers to account for demographic variables, tobacco and alcohol use, drug history, medical history and presence of the apolipoprotein E ε4 (APOE4), which is considered one of the largest genetic risk factors for the development of Alzheimer’s and dementia.

The study yielded 1,895 eligible, cognitively normal subjects, with a mean baseline age of 78.5 years. Of the participants 524 (27.7%) developed incidence of MCI over an average follow-up time of 4.4 years. Those who developed mild cognitive impairment were typically older, more likely to have comorbid diabetes, hypertension and/or coronary artery disease, and were much more likely to carry APOE4. Mean weight-change among those with MCI was greater than it was among those who did not develop MCI. It is important to note that while men who developed MCI had significantly greater mean weight-loss per decade, there was not a significant difference displayed among women.

Adjusting for traits including sex, APOE4 carrier status and education, the study demonstrated that a greater decline in weight from midlife is associated with increased risk of MCI. On average, losing 5 kg per decade correlated to a 24% increased risk of MCI. Further adjustment for potential confounding variables like drug problems, depression, diabetes, hypertension, heart disease, smoking, alcohol use, and stroke did not eliminate this association’s presence. After adjustment, the effect sizes for men were still much greater than in women, but both sexes demonstrated statistically significant results. Of note, the association of increased weight-loss during aging and raised incidence rate of MCI was demonstrated significantly regardless of whether, at midlife, the patients were normal weight, underweight, overweight, or obese.