Weight Loss Improves Cognition in Obese Patients With MCI

Pauline Anderson

January 11, 2016

Older obese patients with mild cognitive impairment (MCI) who intentionally lose weight experience improved memory, executive function, and language, a new study has found.

Many of these cognitive improvements appeared to be strongest in younger patients and those with the APOE4 genotype.

The results suggest that clinicians should encourage obese patients with MCI to lose excess weight through caloric restriction, said lead author Nidia Celese Horie, PhD, Obesity and Metabolic Syndrome Group, São Paulo University, Brazil.

Dr Nidia Celese Horie

Their findings were published online December 29, 2015, in the Journal of Clinical Endocrinology and Metabolism.

The study included 80 mostly female participants with MCI (mean age, 68.1 years). Their body mass index (BMI) ranged from 30 to 49.5 kg/m2), and 26.3% were APOE4 carriers.

Participants were advised to engage in at least 150 minutes of moderate-intensity aerobic activity or walking per week. Those with conditions that limited activity were advised to be as physically active as possible.

All patients received conventional medical care. Half also had regular nutritional counseling aimed at promoting healthy eating habits and weight loss through calorie restriction.

Researchers gave participants a neuropsychological battery of tests that assessed various aspects of cognition. They also recorded level of physical activity using the International Physical Activity questionnaire short version and classified patients as active (150 or more minutes per week) or sedentary.

During the 12-month study, five women were lost to follow up (two in each group dropped out and one in the conventional care group died of pneumonia).

BMI decreased by an average of 1.7, and 43.8% of patients lost more than 5% of their initial body weight. (The goal was 10%.)

There was improvement on most of the cognitive tests in both groups. After adjustment for education, sex, physical activity, and baseline tests, decreased BMI was associated with improvements in global cognition (Montreal Cognitive Assessment and cognitive session of CAMDEX), verbal memory (Rey Auditory Verbal Learning Test), language (phonemic verbal fluency), and executive function (Modified Wisconsin Card Sorting Test).

"The study showed a correlation between weight loss through diet and cognitive change: the more you lose, the more you improve," Dr Horie told Medscape Medical News.

Because the weight loss goal wasn't reached, Dr Horie said that he feared there would be no difference in cognition between the two groups. "It was a pleasant relief to see that even with a conservative weight loss, the results were there."

Verbal memory was the area that seemed to benefit the most from weight loss. For each increment of BMI (1 kg/m2) lost, there was an increase in 1.81 standard deviation on the test score, said Dr Horie.

Younger Patients

For verbal memory and language, the effect of weight loss was more beneficial for younger patients. In fact, for language, losing weight in those older than age 70 years was correlated with worsening of scores.

Older patients typically have more neurologic damage, explained Dr Horie. "Maybe after you have widespread amyloid plaques, controlling risk factors is no longer enough. The neuropathology in older patients is probably less flexible."

A decrease in BMI among APOE4 carriers, who have a greater dementia risk, was more beneficial for executive function. "It's a sign that these patients might get an extra benefit from weight loss, but as this group is at particular risk for dementia, they need to be followed even more carefully," said Dr Horie.

As early as possible, these APOE4 carriers should avoid other risk factors for dementia, which in addition to obesity include diabetes, she added.

Various clinical variables were linked to cognition in the study. For example, increased plasma leptin was associated with improved attention (Digit Span Forward), with a similar trend in executive function.

As well, reductions in homeostasis model assessment-estimated insulin resistance, C-reactive protein, and intake of carbohydrates and fats were all associated with improvement in cognitive tests.

Lean body mass did not change among study participants. As a safety analysis, researchers tested physical function before and after the intervention and found that performance on the Short Physical Performance Battery, gait speed, and muscle function (measured by the Time to Sit/Get Up test) improved significantly.

The number of patients considered physically active increased from 62.5% to 70.7%, but not significantly (P = .282). "From other studies, we know that exercise can be neuroprotective, but as it did not change (in this study), and supervised exercise was not an active part of the intervention, we can understand why it did not influence the outcome," said Dr Horie.

Improvements in memory and executive function were unlikely to be attributable only to a learning effect because the study continued for 12 months, said the authors. They recognized, however, that management of comorbidities during the study may have contributed to the improvement.

Although all obese patients with MCI should lose weight through cutting calories, it's important to avoid undernutrition, stressed Dr Horie.

"We didn't have enough patients who lost over 10% of their body weight to say that it's completely safe to continue with the weight loss beyond that level, but we can say that losing between 3% to 10% — which is what the majority of study subjects lost — is safe."

Lifestyle Importance

Asked for his view of the findings, Ron Petersen, MD, PhD, director, Mayo Clinic Alzheimer's Disease Research Center and Mayo Clinic Study of Aging, Rochester, Minnesota, said it adds to the growing literature showing that lifestyle factors can be important in improving cognitive function as people age. 

Dr Petersen pointed out similarities of these findings to another trial, the Finnish Geriatric Intervention Study to Prevent Disability (FINGER), published online in March 2015 in The Lancet. That 2-year randomized controlled trial found that an intervention including diet, exercise, cognitive training, and vascular risk monitoring helped to improve or maintain cognitive function.

"That study suggested that those individuals who were at higher risk with respect to cardiovascular factors may have the most to gain," he said.

Similarly, this new study "suggested that weight loss in obese individuals can have positive cognitive outcomes."

The authors have disclosed no relevant financial relationships.

J Clin Endocrinol Metab. Published online December 29, 2015. Abstract


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