The lifetime accumulation of multimorbidity and its influence on dementia risk: a UK Biobank Study

The number of people living with dementia worldwide is projected to reach 150 million by 2050, making prevention a crucial priority for health services 1 . The co-occurrence of two or more chronic health conditions, termed multimorbidity, occurs in up to 80% of dementia patients 2 , raising the potential of multimorbidity as an important risk factor for dementia. However, precise understanding of which specific conditions, as well as their age of onset, drive the link between multimorbidity and dementia is unclear. We defined the patterns of accumulation of 46 chronic conditions over their lifetime in 282,712 individuals from the UK Biobank. By grouping individuals based on their life-history of chronic illness, we show here that risk of incident dementia can be stratified by both the type and timing of their accumulated chronic conditions. We identified several distinct clusters of multimorbidity, and their associated risks varied in an age-specific manner. Compared to low multimorbidity, cardiometabolic and neurovascular conditions acquired before 55 years were most strongly associated with dementia. Acquisition of mental health and neurovascular conditions between the ages of 55 and 70 was associated with an over two-fold increase in dementia risk compared to low multimorbidity. The age-dependent role of multimorbidity in predicting dementia risk could be used for early stratification of individuals into high and low risk groups and inform targeted prevention strategies based on a person’s prior history of chronic disease.