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People with two or more chronic conditions (multimorbidity) in midlife had a higher risk of subsequent dementia, a prospective cohort showed.

Midlife multimorbidity more than doubled the risk of dementia later in life, reported Céline Ben Hassen, PhD, of Université de Paris, and colleagues, in . Every 5-year younger age at multimorbidity onset upped dementia risk by 18%.

"The specific contribution of this study is to show that early onset of multimorbidity is particularly harmful," co-author Archana Singh-Manoux, PhD, also of Université de Paris, told 木瓜直播.

"Multimorbidity -- the occurrence of two or more chronic diseases -- is increasingly common and not confined to older ages," she noted. "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 that dementia develops over a long period of time, perhaps as long as 20 years," Singh-Manoux pointed out. "Early onset of multimorbidity implies that there are 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 cohort who were ages 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 through 2019. Covariates included age, sex, ethnicity, education, diet, and lifestyle behaviors 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 (1.56 incidence rate difference per 1,000 person years; adjusted HR 2.44, 95% CI 1.82-3.26).

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 (HR 4.96, 2.54-9.67). 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.

"Brain health is likely to be a lifelong process, and the lack of curative solutions for dementia highlights the importance of prevention, starting early in midlife," Singh-Manoux noted.

"For those with a first chronic condition, it is important to manage the condition so that a second chronic condition is avoided," she said. "Data from high-income countries show the increasing prevalence of multimorbidity in midlife, and this is likely to have implications for the cognitive status of individuals at older ages."

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