Dementia Accompanying Cardiometabolic Disease: Does It Come Down to Genetics?

There may be a limit to how much reducing cardiometabolic disease would lower the risk of dementia in older people genetically predisposed to both conditions, a twin study suggested.

Twins over age 60 developed dementia at an incidence of 16.9% over a median 15.4 years of follow-up in a cohort counting over 17,000 individuals in the Swedish Twin Registry, the largest population-based twin registry in the world, according to researchers led by Abigail Dove, MA, a PhD student at Karolinska Institutet in Solna, Sweden.

Having one cardiometabolic disease (HR 1.42, 95% CI 1.27-1.58) or cardiometabolic multimorbidity (HR 2.10, 95% CI 1.73-2.57) in mid- and late-life was each associated with incident dementia in this cohort. These associations were applicable to both Alzheimer's disease and vascular dementia and were particularly strong with cardiometabolic disease developing at a younger age.

"These findings add to the growing evidence of a connection between cardiometabolic multimorbidity and both vascular and neurodegenerative forms of dementia and highlight the need for special monitoring of individuals who develop type 2 diabetes, heart disease, or stroke in mid-life in order to reduce their risk of developing dementia in older age," the investigators reported in European Heart Journal.

However, in a matched analysis of 356 twin pairs, the link between cardiometabolic disease and dementia was present in dizygotic twins (HR 1.55, 95% CI 1.15–2.09) but not monozygotic, genetically identical twins (HR 0.99, 95% CI 0.50–1.98; P=0.005 for interaction).

"The relatively small number of monozygote twins warrants caution, but, if holding true, this intriguing finding leads to the conclusion that most of the association between cardiometabolic multimorbidity and subsequent dementia risk is due to a shared genetic background rather than to the detrimental effects exerted by cardiometabolic conditions themselves," noted endocrinologists Gian Paolo Fadini, MD, PhD, and Mario Luca Morieri, MD, both of the University of Padova in Padua, Italy.

In an accompanying editorial, they said the report by Dove's group seems to argue against opportunities to prevent dementia by controlling cardiometabolic multimorbidity. The finding of a particularly large impact of mid-life cardiometabolic diseases on dementia, they suggested, is potentially being driven by a stronger genetic predisposition.

"However, that trajectory is not necessarily going to be inescapable. There is still a chance of slowing down cognitive decline by taking care of the environment that pervades a [person's] life in the broader sense and actively tackling all deprivation statuses," the editorialists wrote.

Although no effective therapy exists for dementia, better lifestyle has been tied to lower risk of dementia even in people at high genetic risk for Alzheimer's disease. Known risk factors for dementia include inadequate physical activity, hypertension, obesity, cigarette smoking, excessive drinking, diabetes, depression, and hearing loss.

The present observational study relied on Swedish Twin Registry data covering older individuals who were recruited from March 1998 and December 2002. Cardiometabolic diseases -- namely type 2 diabetes, heart disease, and stroke -- and dementia were ascertained from medical records. Participants were 17,913 people free of dementia (mean age 70.1 years, 55% women).

At baseline, 18.5% of people had one cardiometabolic disease and 4.7% had at least two. Compared with peers without cardiometabolic disease, these individuals tended to be older and more likely to be single men with fewer years of formal education.

Dove and co-authors acknowledged that their reliance on Swedish medical records meant they may have missed people with cardiometabolic disease or incident dementia. The records also included self-reported sociodemographic and lifestyle variables that could be subject to patient recall bias.

The team suggested more research on the genes and common biological pathways that may be involved in the cardiometabolic disease-dementia link.

Fadini and Morieri urged confirmation of the study's findings in people with other cardiometabolic-renal conditions, such as hypertension, dyslipidemia, and obesity.

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