Patterns and trajectories of multimorbidity prior to dementia: a UK Biobank study

Abstract

AbstractBackgroundThe co‐occurrence of multiple long term conditions (LTCs), termed multimorbidity, is a risk factor for dementia. However, we lack an understanding of how and when specific LTCs accumulate over time to impact dementia risk.Method338,270 individuals from the UK Biobank with linked electronic health records up to January 2022 were studied, excluding those with either a dementia diagnosis or age of latest follow up < 65 years. LTC diagnoses were derived using hospital episode statistics and GP records (age of diagnosis computed using month/year of birth and month/year of diagnosis). We performed an age‐stratified analysis in which we a) cluster individuals based on 43 non‐dementia LTCs diagnosed within age bins (0‐55, 55‐65, 65‐70 years), and b) compute risk of incident dementia using logistic regression with multimorbidity cluster as predictor and incident dementia as outcome. Diagnosis data was submitted to PCA, and the resulting factor scores were kMeans‐clustered. 6 clusters were derived per age bin.ResultWe named clusters based on the most prevalent LTCs within that cluster (Figure 1). Cardiometabolic, arthritis, gastrointestinal, and mixed clusters existed at all ages. Mental health and respiratory clusters were present exclusively in the younger age bin (0‐55) whereas hypertension and eye disorder clusters were exclusive to older ages (55‐65 and 65‐70). Across the lifespan, compared to being disease free, multimorbidity was significantly associated with incident dementia (OR>1). We also observed age‐specific multimorbidity preceding dementia onset. From 0‐55 years, being in the mixed cluster presented the highest dementia risk (OR = 5.13, 95% CI = [4.61, 5.73]). Being in the cardiometabolic cluster was associated with highest risk in 55‐65 (OR = 6.24 [5.48, 7.1]) and 65‐70 (OR = 6.99 [5.91, 8.27]) ranges. The most predictive trajectory of incident dementia involved the mixed cluster at 55, followed by the cardiometabolic clusters from 55‐65 and 65‐70. Table 1 displays the top 10 trajectories associated with dementia. All p‐values are bonferroni‐holmes corrected and < 0.01.ConclusionWe present multimorbidity pathways linked to increased risk of dementia. We describe how and when diseases cluster together prior to dementia diagnosis.