Description of the research
What was the goal of your research or experiment?
Our goal was to investigate the relationship between insulin resistance-related diseases (e.g., type 2 diabetes mellitus, obesity, cardiovascular diseases) and cognitive functioning (e.g., memory, attention, speed of processing, executive functioning). By reviewing and summarising findings from earlier publications, we can combine evidence from multiple studies.
How did you measure or test this?
We performed a systematic review on the most important international, scientific literature databases (i.e., PubMed, Scopus, and Web of Science), looking for previous studies evaluating this relationship. We focussed on studies that used the largest population-based cohort from United Kingdom: the UK Biobank study cohort. This is a large prospective study that contains information about the general health of middle-aged and older people (40 years and older) across the United Kingdom. From 2006 to 2010, approximately 500,000 individuals were recruited, and a detailed characterisation of sociodemographic, lifestyle, environmental factors, medical history, physical measures, and cognition was conducted.
What were the main results or findings?
This literature review of UK Biobank studies found substantial evidence for an association between cognitive performance and diseases and traits related to insulin resistance. This means that middle-aged and older adults with obesity, type 2 diabetes mellitus, hypertension, and/or coronary artery disease were more likely to perform worse on various cognitive domains. The most consistent findings are related to worse performance on verbal and numerical reasoning, as well as processing speed, in individuals with insulin resistance.
What does this mean?
Insulin resistance may influence cognitive functions and mental health. It has been suggested that these associations could be mediated by alterations in immune-inflammation, brain white matter integrity/connectivity, or structural alterations in the brain. However, the reviewed studies have only looked at associations. Therefore, we do not know whether insulin resistance causes the observed cognitive deficits.
Considering the worldwide increasing levels of insulin resistance-related multimorbidity and public health concerns about rising rates of cognitive decline, our findings draw the attention of clinicians to the importance of primary and secondary prevention in people with cardio-metabolic diseases and insulin resistance. Such prevention may include the promotion of a healthy lifestyle and diet, exercise, mental health, and early screening and treatment.
What is the next step?
One step is to gain a better understanding of the causal relationship between cognitive impairment and cardio-metabolic diseases linked to insulin resistance. For this we need to better understand the
mechanisms of insulin signalling in the brain. Researchers should therefore examine the potential contribution of immune-inflammatory, oxidative, and central insulin signalling mechanisms. In addition, research examining the effect of genes implicated in insulin signalling, immune-inflammation, and Hypothalamic-Pituitary-Adrenal axis modulation on both cognition and insulin resistance-somatic diseases is needed.
Another direction of future research is the possible repurposing of hypoglycaemic drugs – currently used to lower blood glucose levels – in the treatment of cognitive deficits seen in various neuropsychiatric disorders. Large-scale randomised clinical trials are required to confirm the safety and efficacy of these drugs in the treatment of cognitive deficits. Such studies could also further inform our understanding of the shared pathophysiological mechanisms. Cognitive impairment is still one of the most challenging symptom domains to tackle with available pharmacological therapy. As a result, gaining a deeper understanding of the processes underlying the reported links between insulin resistance and cognitive impairment will be critical in identifying potential new targets for pharmacological and/or behavioural intervention in patients with neuropsychiatric disorders.
Title: The link between cognition and somatic conditions related to insulin resistance in the UK Biobank study cohort: a systematic review
Authors: Giuseppe Fanelli*, Nina Roth Mota*, Jordi Salas-Salvadó, Monica Bulló, Fernando Fernandez-Aranda, Lucíaa Camacho-Barcia, Giulia Testa, Susana Jiménez-Murcia, Valérie Bertaina-Anglade, Barbara Franke, Geert Poelmans, Veerle van Gils , Willemijn J. Jansen, Stephanie J.B. Vos, Theresa Wimberley, Søren Dalsgaard, Csaba Barta, Alessandro Serretti, Chiara Fabbri, Janita Bralten
*These two authors contributed equally
Journal: Neuroscience and Biobehavioral Reviews