Thursday, 11 August, 2022
HomeEditor's PickEarly onset comorbidities linked to higher risk of later dementia – 30-year...

Early onset comorbidities linked to higher risk of later dementia – 30-year study

People with two or more chronic conditions in midlife had a substantially higher risk of subsequent dementia, a prospective cohort  study analysing data from more than 10,000 British civil servants, has shown.

Midlife multimorbidity more than doubled the risk of dementia later in life, according to the study, and every five-year younger age at multimorbidity onset upped dementia risk by 18%.

The research, published in The BMJ, was carried out by Céline Ben Hassen, of Université de Paris, and colleagues. “The specific contribution of this study is to show that early onset of multimorbidity is particularly harmful,” said co-author Archana Singh-Manoux, also of Université de Paris.

“Multimorbidity, or the occurrence of two or more chronic diseases, is increasingly common and not confined to older ages,” she said. “We show a robust association between multimorbidity and dementia, which was not driven by a specific combination of chronic diseases.

“These findings need to be considered in light of the fact that we now know dementia develops over a long period of time, perhaps as long as 20 years. Early onset of multimorbidity implies there is a range of pathophysiologic alterations linked to chronic diseases that are then involved in increasing risk of dementia at older ages.”

The study included data from 10,095 British civil servants in the Whitehall II cohort who were aged 35-55 and dementia-free in 1985-1988.

Multimorbidity was defined as the presence of at least two chronic conditions from a list of 13 disorders, including hypertension, diabetes, coronary heart disease, depression and other mental disorders, cancer, chronic kidney disease, rheumatoid arthritis, and chronic lung disease.

Subsequent cases of dementia were identified by hospital and death records up to 2019. Covariates included age, sex, ethnicity, education, diet, and lifestyle behaviours including smoking and physical activity.

The prevalence of multimorbidity was 6.6% at age 55 and 31.7% at age 70. A total of 639 cases of incident dementia occurred over a median follow-up of 31.7 years.

The strongest associations were seen in those with multimorbidity at age 55, with weaker associations for onset of multimorbidity at older ages. Multimorbidity at age 55 was tied to 2.4 times higher risk of dementia compared with having none or one chronic condition.

Severity of multimorbidity accentuated the importance of younger age. Compared with participants with none or one condition, people with three or more chronic conditions at age 55 had nearly five-fold higher dementia risk. The risk was 1.7-fold higher when onset of multimorbidity was at age 70.

Trends were similar using death instead of incident dementia as the outcome measure.

The study had several limitations, the researchers acknowledged. Dementia ascertainment was based on electronic health record data, which may lead to misclassification in some cases. Whitehall II study participants all were employed when they joined the cohort and may have been healthier than the general population. In addition, the study could not assess the severity of individual chronic conditions or the role played by drug interactions.

Study details

Association between age at onset of multimorbidity and incidence of dementia: 30-year follow-up in Whitehall II prospective cohort study

Céline Ben Hassen, Aurore Fayosse, Benjamin Landré, Martina Raggi, Mikaela Bloomberg, Séverine Sabia, Archana Singh-Manoux.

Published in The BMJ on 2 February 2022


To examine the association of midlife and late life multimorbidity, including severity of multimorbidity, with incident dementia.

Prospective cohort study.

Civil service departments in London (Whitehall II study, study inception in 1985-88).

10,095 participants, aged 35 to 55 at baseline.

Main outcome measure
Incident dementia at follow-up between 1985 and 2019. Cause specific Cox proportional hazards regression was used to examine the association of multimorbidity overall and at age 55, 60, 65, and 70 with subsequent dementia, taking into account the competing risk of death.

The prevalence of multimorbidity (≥2 chronic diseases) was 6.6% (655/9937) at age 55 and 31.7% (2464/7783) at age 70; 639 cases of incident dementia occurred over a median follow-up of 31.7 years. After adjustment for sociodemographic factors and health behaviours, multimorbidity at age 55 was associated with subsequent risk of dementia (difference in incidence rate per 1000 person years 1.56, 95% confidence interval 0.62 to 2.77; hazard ratio 2.44, 95% confidence interval 1.82 to 3.26). The association weakened progressively with older age at onset of multimorbidity. At age 65, onset of multimorbidity before age 55 was associated with 3.86 (1.80 to 6.52) per 1000 person years higher incidence of dementia (hazard ratio 2.46, 1.80 to 2.26) and onset between 60 and 65 was associated with 1.85 (0.64 to 3.39) per 1000 person years higher incidence (1.51, 1.16 to 1.97). Severity of multimorbidity (≥3 chronic diseases) at age 55 was associated with a 5.22 (1.14 to 11.95) per 1000 person years higher incidence of dementia (hazard ratio 4.96, 2.54 to 9.67); the same analyses at age 70 showed 4.49 (2.33 to 7.19) per 1000 person years higher incidence (1.65, 1.25 to 2.18).

Multimorbidity, particularly when onset is in midlife rather than late life, has a robust association with subsequent dementia. The increasingly younger age at onset of multimorbidity makes prevention of multimorbidity in people with a first chronic disease important.


The Whitehall II study


BMJ article – Association between age at onset of multimorbidity and incidence of dementia: 30 year follow-up in Whitehall II prospective cohort study (Open access)


See more from MedicalBrief archives:


'Protective effect of obesity' against dementia challenged in 2 studies


Large data-set studies on CVD and multi-morbidity


WHO issues its first guidelines on reducing dementia risk


Psychological distress a factor for future dementia risk




MedicalBrief — our free weekly e-newsletter

We'd appeciate as much information as possible, however only an email address is required.