The metabolic dysfunction of type 2 diabetes is known to accelerate the pathologies of aging. A range of mechanisms are involved, the most prominent of which is elevated chronic inflammation. Type 2 diabetes is a lifestyle condition caused, in the vast majority of cases, by being very overweight. Excess visceral fat tissue, required to produce the metabolic syndrome that leads into type 2 diabetes, accelerates the production of pro-inflammatory and generally disruptive senescent cells, but also produces inflammation via other mechanisms, such as the release of DNA debris from dying fat cells. Diabetes also features increased levels of circulating advanced glycation end-products (AGEs), and this sugary metabolic waste provokes inflammatory behavior via the receptor for AGEs (RAGE).
Neurodegenerative conditions are also driven and characterized by chronic inflammation. It might be expected that years of raised chronic inflammation due to excess fat tissue and an aberrant diabetic metabolism will act to accelerate neurodegeneration, just as it does for all of the other common age-related conditions. The mechanisms involved may be direct, such as a disruption of the supporting immune cells in the brain via inflammatory signaling, as activated and senescent microglia are implicated in the progression of conditions such as Alzheimer's disease. It may be more indirect, involving accelerated cardiovascular aging (hypertension, atherosclerosis, blood-brain barrier dysfunction, reduced capillary density, and so forth) that produces harmful outcomes that contribute to neurodegeneration, such as a reduced blood supply and increased rupture of small blood vessels in brain tissue.
Scientists have demonstrated that normal brain aging is accelerated by approximately 26% in people with progressive type 2 diabetes compared with individuals without the disease. The results further suggest that by the time type 2 diabetes is formally diagnosed, there may already be significant structural damage to the brain. There is already strong evidence linking type 2 diabetes with cognitive decline, yet few patients currently undergo a comprehensive cognitive assessment as part of their clinical care. It can be difficult to distinguish between normal brain aging that begins in middle age, and brain aging caused or accelerated by diabetes.
The team made use of the largest available brain structure and function dataset across human lifespan: UK Biobank data from 20,000 people aged 50 to 80 years old. This dataset includes brain scans and brain function measurements and holds data for both healthy individuals and those with a type 2 diabetes diagnosis. They used this to determine which brain and cognitive changes are specific to diabetes, rather than just aging, and then confirmed these results by comparing them with a meta-analysis of nearly 100 other studies.
We characterized neurocognitive effects independently associated with T2DM and age in a large cohort of human subjects from the UK Biobank with cross-sectional neuroimaging and cognitive data. We then proceeded to evaluate the extent of overlap between the effects related to T2DM and age by applying correlation measures to the separately characterized neurocognitive changes. Our findings were complemented by meta-analyses of published reports with cognitive or neuroimaging measures for T2DM and healthy controls (HCs).
T2DM was associated with marked cognitive deficits, particularly in executive functioning and processing speed. Likewise, we found that the diagnosis of T2DM was significantly associated with gray matter atrophy. The structural and functional changes associated with T2DM show marked overlap with the effects correlating with age but appear earlier, with disease duration linked to more severe neurodegeneration. The neurocognitive impact of T2DM suggests marked acceleration of normal brain aging. T2DM gray matter atrophy occurred approximately 26% ± 14% faster than seen with normal aging.