The effects of weight loss and metformin on cognition among breast cancer survivors: Evidence from the Reach for Health study

Abstract

Objective Breast cancer survivors experience problems with cognition that interfere with daily life and can last for years. In the general population, obesity and diabetes are risk factors for cognitive decline, and weight loss can improve cognition; however, the impact of intentional weight loss on cancer survivors' cognition has not been tested. We investigated the impact of weight loss and metformin on changes in cognitive function in a sample of breast cancer survivors. Methods Overweight/obese postmenopausal breast cancer survivors (n = 333) were randomized to a weight loss intervention versus control and metformin versus placebo in a 2 × 2 factorial design. Outcomes were changes in five cognitive domains from baseline to 6 months measured by objective neurocognitive tests. Results There were no statistically significant intervention effects for the metformin or weight loss interventions in five neurocognitive domains. Baseline body mass index (BMI) was a significant effect modifier of the changes in verbal functioning for the weight loss (P = 0.009) and metformin interventions (P = 0.0125). These effect modifications were independent of percent weight loss achieved during the 6‐month study period. Conclusions This randomized controlled trial of weight loss and metformin interventions that examined changes to cognition among breast cancer survivors suggests that these interventions may not improve cognitive functioning among breast cancer survivors in general. However, weight loss may improve verbal functioning among individuals with a higher BMI.

The effect of metformin on cognitive function: A systematic review and meta-analysis

“…In four double-blind randomized controlled studies (DRCTs), the effect of metformin versus placebo on cognitive performance was evaluated in 325 patients with and without diabetes (DM). The dose of metformin used in these studies was 1500–2000 mg per day and the duration of treatment was 16–48 weeks (Luchsinger et al, 2016; Guo et al, 2014; Hartman et al, 2019; Imfeld et al, 2012). The quality of all trials was high.…”

“…Out of four trials, three (Guo et al, 2014; Hartman et al, 2019; Luchsinger et al, 2016) were eligible for inclusion in the meta-analysis. The pooled effect was non-significant with SMD (standardized mean difference) equal to 0.50, 95% CI = [−0.2, 1.20], and I 2 = 89.3% in a random-effect analysis (Figure 2).…”

“…Some studies found the protective effect of metformin against cognitive decline in diabetes patients (Ng et al, 2014; Samaras et al, 2020; Zhou et al, 2020) and enhancement of brain function in the prediabetes animal model (Pratchayasakul et al, 2020) while other studies did not report any significant effect (Hartman et al, 2019; Luchsinger et al, 2017) or even reported a negative effect of metformin on cognitive function (Porter et al, 2019). Our findings in this study are similar to Luchsinger et al’s and Hartman et al’s studies results (Hartman et al, 2019; Luchsinger et al, 2017) that found no significant effect. Porter et al’s study showed that metformin in older adults without dementia is associated with an increased risk of cognitive dysfunction and vitamin B deficiency may play a role in this disorder (Porter et al, 2019).…”

The impact of metformin use on the outcomes of locally advanced breast cancer patients receiving neoadjuvant chemotherapy: an open-labelled randomized controlled trial

“…Additionally, Hartman et al (2019) found that metformin might not positively affect neurocognitive functioning among BC survivors in general. However, verbal functioning could be enhanced by weight loss among individuals with higher BMI 85 .…”

A Systematic Review Focused On Understanding the Effects of Modifiable Factors in Patients who Suffer from Chemotherapy Induced Cognitive Impairments or “Chemobrain”

“…The study concluded that use of metformin on obese cancer survivors did not provide any improvements in cognitive complaints, but did show a signi cant improvement in verbal functioning (p = 0.009). 34 Lawrence et al used donepezil as an intervention in 32 BCS with reported CICI compared to control group (n = 32). The intervention group performed slightly better on the Hopkins Verbal Learning Test-Revised (p = 0.033) and the HVLT-R Discrimination (p = 0.036) compared to the control group.…”