![]() ![]() Crucially, long-term retrospective trajectories of cardio-metabolic factors before dementia onset have not been described among populations with type 2 diabetes apart from one small study. A few studies have explored cardio-metabolic factor trajectories within the general population. However, the levels of cardio-metabolic factors and their effects on dementia risk may vary over the lifespan, presenting challenges to identify targets for timely interventions. Ĭardio-metabolic factors present as potentially modifiable risk factors in people with type 2 diabetes, as mid-life hypertension, obesity, physical inactivity, and dyslipidaemia each independently increase dementia risk in the general population. Although hyperglycaemia has been linked to increased dementia risk, intensified glycaemic control and diabetes-specific medical treatments have not shown to change the course of dementia development. These early pre-clinical stages are acknowledged as potential targets for secondary prevention and future disease-modifying pharmaceutical therapies. These pathologies, however, can occur in the absence of diabetes and are known to progressively accumulate over several years before the clinical onset of cognitive decline and dementia. Several underlying mechanisms have been proposed including cerebral insulin dysregulation, cerebrovascular abnormalities, advanced protein glycation, oxidative stress and cerebral accumulation of several proteins. However, the causal pathways of diabetes-related dementia risk are not well-understood and effective preventive approaches are currently limited. Type 2 diabetes represents a potential intervention point, as up to 10% of dementia cases may be attributable to type 2 diabetes. In England, one fifth of people aged ≥ 65 years with dementia have diabetes, leading to increasingly complex clinical and social care needs.ĭespite dementia being a leading cause of death, our understanding of its risk factors and prevention has advanced slower than that for other major non-communicable diseases. People with type 2 diabetes have a two-fold increased dementia risk. Type 2 diabetes and dementia are both increasing in prevalence, costly to health systems, and major contributors to comorbidities and mortality globally. Future investigations which address associations between cardiometabolic factors and dementia should account for potential non-linear relationships and consider the timeframe when measurements are taken. Our findings suggest that a long follow-up is crucial to minimise reverse causation arising from changes in cardio-metabolic factors during preclinical dementia. However, absolute group differences were small. Differences in levels of cardio-metabolic factors were observed up to two decades prior to dementia diagnosis. Mean blood lipid levels (total cholesterol, LDL, HDL) and glycaemic measures (fasting plasma glucose and HbA1c) were generally higher in the dementia group compared with those without dementia and followed similar patterns of change. Mean body mass index followed a steeper non-linear decline from 11 years before diagnosis in the dementia group. In the dementia group, mean systolic blood pressure increased 16–19 years before dementia diagnosis compared with patients without dementia, but declined more steeply from 16 years before diagnosis, while diastolic blood pressure generally declined at similar rates. Multivariable multilevel piecewise and non-piecewise growth curve models assessed retrospective trajectories of cardio-metabolic factors by dementia status from up to 19 years preceding dementia diagnosis (dementia) or last contact with healthcare (no dementia). 23,546 patients developed dementia mean (SD) follow-up was 10.0 (5.8) years. Annual mean levels of eight routinely measured cardio-metabolic factors were extracted from the Clinical Practice Research Datalink. To assess 20-year retrospective trajectories of cardio-metabolic factors preceding dementia diagnosis among people with type 2 diabetes (T2D). We identified 227,145 people with T2D aged > 42 years between 19.
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