Early multimorbidity associated with dementia

A prospective cohort study of over 10,000 participants followed up for more than 30 years finds a robust association between midlife-onset multimorbidity and subsequent dementia.

The Whitehall II study assessed incident dementia among 10,095 participants (age, 35–55 years at baseline) from the civil service departments in London, UK, between 1985 and 2019. Follow-up clinical examinations took place approximately every 4–5 years since baseline. Data on multimorbidity were retrieved from UK National Health Service (NHS) electronic health records. [BMJ 2022;doi:10.1136/bmj-2021-068005]

Multimorbidity was defined as the presence of at least two chronic conditions out of a predefined list of 13 chronic diseases: coronary heart disease, stroke, heart failure, diabetes, hypertension, cancer, chronic kidney disease (CKD), chronic obstructive pulmonary disease (COPD), liver disease, depression, mental disorders other than depression, Parkinson’s disease, and arthritis/rheumatoid arthritis.

“Over a median follow-up of 31.7 years, a total of 639 cases of dementia were ascertained. The most frequent chronic condition among people with dementia was hypertension, followed by coronary heart disease, depression, and diabetes,” reported the researchers.

The prevalence of all individual chronic conditions increased with age, with some chronic conditions showing a steady increase (eg, diabetes) and others a more rapid increase between the age of 65 and 70 years (eg, COPD, CKD). At 55 years of age, 63.0 percent of participants had none of the evaluated 13 chronic diseases, while at the age of 70 years, only 29.8 percent of participants remained chronic disease–free. At the age of 55 years, 6.6 percent of participants reported multimorbidity, while 31.7 percent reported multimorbidity at 70 years of age.

“Compared with people without any of the 13 chronic conditions, multimorbidity at 55 years of age was associated with a higher incidence rate [difference, 1.56 per 1,000 person-years; 95 percent confidence interval (CI), 0.62 to 2.77] and a hazard ratio [HR] of subsequent dementia of 2.44 [95 percent CI, 1.82 to 3.26] in analyses that included adjustment for all covariates,” noted the researchers. “When we considered multimorbidity status at 60, 65, and 70 years of age, younger age at onset was associated with higher risk of dementia [all p for trend <0.001].”

In analyses of individual chronic diseases, cancer (HR, 1.06; 95 percent CI, 0.85 to 1.31) was not associated with dementia when treated as time-varying variable or in the age-specific analyses. Apart from Parkinson’s disease, mental disorders had the highest HR (13.51; 6.53 to 27.95) at age 60, with a progressive decrease in association with age, such that prevalent mental disorders at the age of 70 years had a HR for dementia of 2.05 (95 percent CI, 0.97 to 4.35). The association of dementia with stroke, heart failure, diabetes, COPD, and mental disorders weakened when these chronic conditions were measured at older ages, whereas an opposite pattern was observed with depression.

“To our knowledge, our study is the first to show that multimorbidity in midlife is associated with higher risk of dementia at older ages, even more so when onset of multimorbidity is in midlife rather than late life. These findings highlight the role of prevention and management of chronic diseases over the course of adulthood to mitigate adverse outcomes in old age,” concluded the researchers.