Cardiovascular risk factors and their relationship to age of onset of Alzheimer’s disease in people with Down syndrome

Abstract

AbstractBackgroundPeople with Down syndrome (DS) are at ultra‐high risk of developing Alzheimer’s dementia (AD). This is primarily due to the triplication of amyloid precursor protein on chromosome 21. Despite common genetic drivers there are large variations in the age of AD onset. In sporadic AD poor cardiovascular health has been associated with increased risk of AD. It has not been established whether the same risks apply to people with DS.MethodLarge population‐based cohort study utilising data from UK‐based primary care electronic health records. Measurements of nine cardiovascular parameters were used to analyse patterns across adulthood. These were systolic blood pressure (SBP), diastolic blood pressure (DBP), pulse pressure (PP), body mass index (BMI), total cholesterol, high and low density lipoproteins, triglycerides, and glycated haemoglobin (HbA1c). Survival curves were fitted with hazard ratios (HR) and crude incident rates calculated using cardiovascular parameters measured between age 25‐34 years as predictor variables and incidence of dementia as the outcome. Age, sex, level of intellectual disability, history of congenital heart disease (CHD), cardiovascular disease, hypothyroidism and diabetes were included as covariates.Result6,424 adults with DS were identified, matched to 23,143 controls. Low PP (<40mmHg), HR 1.45; low DBP (<62mmHg), HR 1.77, and low SBP (<100mmHg), HR 1.83 increased risk of dementia incidence. High SBP (>140mmHg), HR 2.04 increased risk but few people had high values. Raised BMI >25kg/m2 increased incidence dementia risk (HR 1.63). The risk was the same whether someone was overweight or obese. Hypothyroidism, history of CHD, male sex were significant contributors in the models. There was a cumulative effect of risk. People with 1 or 2 risk factors had HRs of 3.15 compared to those with zero risks, whilst people with 3 or more cardiovascular risk factors had HRs of 5.69.ConclusionCardiovascular health in earlier adulthood affects age of AD onset in people with DS. Cardiovascular multi‐morbidity was associated with increased incidence dementia risk suggesting that risks interact in a cumulative fashion. Reducing the number of risks by actively screening and managing medical co‐morbidities in people with DS may therefore help delay the onset of AD. Multi‐domain interventions may be particularly important.