Early Onset Diabetes May Increase Dementia Risk
By Jill Horn
“Type 2 diabetes is most often caused by environmental risk factors such as the consumption of unhealthy, energy-dense foods and a lack of physical activity.”
Type 2 diabetes is a chronic disease associated with serious complications and co-morbidities including cardiovascular disease, stroke, and vascular damage (Javeed et al., 2018). The global prevalence of type 2 diabetes has reached epidemic proportions, affecting about 400 million people worldwide, with a predicted increasing trend in the near future (Zimmet et al., 2016). Type 2 diabetes primarily manifests through progressive deterioration of the body’s sensitivity to the hormone and is most often caused by environmental risk factors such as the consumption of unhealthy, energy-dense foods and a lack of physical activity (Chatterjee et al., 2017). Changes in the gut microbiome, as a result of the Standard American Diet (SAD) resulting in increased intestinal permeability and metabolic endotoxemia have been identified as major risk factors for the disease. Importantly, there has been a recent increase in the prevalence of type 2 diabetes amongst adolescents and young adults, with a disproportional impact on minority groups and people from disadvantaged backgrounds (Dabelea et al., 2014). Furthermore, youth onset of type 2 diabetes shows a unique pathophysiology that differs slightly from the adult condition (Zeitler et al., 2012) and brings about alarming risk factors for comorbid conditions such as cardiovascular disease and an increased risk for dementia (Sarwar et al., 2010; Barbiellini et al., 2021).
“…studies suggests a strong link between type 2 diabetes and the subsequent development of dementia.”
Converging evidence from many different studies suggests a strong link between type 2 diabetes and the subsequent development of dementia (Cheng et al., 2012, Chatterjee et al., 2016, Zhang et al., 2017, Kivimaki et al., 2019). Dementia is characterized by progressive cognitive impairment and manifests as Alzheimer’s disease in most individuals (Ljubenkov et al., 2016). The most salient symptom of Alzheimer’s disease entails impaired formation and retrieval of memories (which is known as anterograde amnesia) and commonly co-occurs with a dysfunction in other cognitive domains (McKhann et al., 2011). Longitudinal observational studies allow scientists to monitor the same patients over long periods of time, therefore enabling direct investigation of a link between subsequent comorbid diseases. Several studies of this kind have reported an increased risk for Alzheimer’s disease in patients with type 2 diabetes (Exalto et al., 2012; Cheng et al., 2012; Gudala et al., 2013), with a longer duration of diabetes being correlated with accelerated subsequent cognitive decline (Rawlings et al., 2019).
“Diabetes onset at a younger age was significantly associated with a higher risk of subsequent dementia…”
A recent longitudinal study specifically investigated the association between the age of diabetes onset and the risk for dementia later in life and found a direct link between the two. Diabetes onset at a younger age was significantly associated with a higher risk of subsequent dementia, with every 5-year earlier onset of diabetes showing a correlation with increased dementia hazard. Possible explanations for these findings include decreased cerebral glucose utilization which has been observed in patients both with type 2 diabetes and Alzheimer’s disease (Kellar et al., 2020; Arnold et al., 2018;Barbiellini et al., 2021). A cross-sectional study in middle-aged adults provides supporting evidence for this hypothesis, as their results demonstrate a negative correlation between insulin resistance and the metabolism of insulin in different brain regions (Willette et al., 2015), suggesting a possible link between systemic and brain insulin resistance. A second hypothesis predicts that microvascular dysfunction leading to reduced regional blood flow as observed in diabetes leads to chronic inflammation, oxidative stress, and increased permeability of the blood-brain barrier, all of which are pathophysiologic factors associated with Alzheimer’s disease as well (Meneilly et al., 2016).
“Targeting early risk factors for cognitive decline will be a crucial component of counter acting the predicted exponential increase in Alzheimer’s disease…”
In the next few years, it will be important to focus on preventative education, enhanced study designs, and patient-centered interventions to combat the accelerating increase in prevalence of type 2 diabetes and simultaneously decrease the risk for dementia. Targeting early risk factors for cognitive decline will be a crucial component of counter-acting the predicted exponential increase in Alzheimer’s disease, which is likely to spike to about 152 million people by 2050 (ADI, 2018).
Well-documented and relatively easily applicable preventative strategies for type 2 diabetes include a traditional Mediterranean type diet, with predominant consumption of plant derived foods, mainly derived from fruits and vegetables, nuts and olive oil. Increased leisure time physical activity (Aune et al., 2015) and decreased sitting and monitor-viewing time are also suggested to reduce diabetes risk (Hamilton et al., 2014). Enhancing research in these domains as well as upscaling educational programs for prevention of both diabetes and dementia will be important components of strategically combatting the rising trend of these diseases, which in many cases involves the adoption of simple lifestyle changes that are known to promote overall physical, gut microbial, and brain health.
Jill Horn is an international student from Switzerland on a pre-med track, currently majoring in Neuroscience at UCLA.