Presymptomatic Atherosclerosis May Contribute to the Development of Alzheimer Disease Later in Life


Heart health may influence long-term brain health as early as middle age.

Atherosclerosis and its associated risk factors may contribute to the development of Alzheimer disease from middle age, according to a study conducted by investigators at the Centro Nacional de Investigaciones Cardiovasculares (CNIC) in Madrid, Spain, and published in The Lancet Healthy Longevity. Atherosclerosis and its associated risk factors are known to contribute to cardiovascular disease (CVD), and these findings show that preventing CV risk factors may decrease a person’s risk of developing Alzheimer disease, the most frequent cause of dementia.

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“Everybody knows that a healthy lifestyle and controlling CVD risk factors are important for preventing a heart attack,” said study author Valentín Fuster, general director at CNIC, in the press release. “Nevertheless, the additional information linking the same risk factors to a decline in brain health could further increase awareness of the need to acquire healthy habits from the earliest life stages.”

The prospective 2021 PESA-CNIC-Santander study evaluated the progression of subclinical atherosclerosis—the buildup of fatty deposits in the arteries—in more than 4000 symptomatic middle-aged adults who had been assessed for symptoms since 2010. After 5 years of monitoring participant brain health with positron emission tomography (PET) imaging, Fuster and other members of the CNIC team (Marta Cortés Canteli and Juan Domingo Gispert) found that patients who developed subclinical atherosclerosis in their carotid arteries, which supplies blood and glucose to the brain, had more CVD risk factors.

Investigators also observed that brain regions associated with Alzheimer disease were metabolically less active in patients who developed subclinical atherosclerosis. Given that brain cells need glucose to function, and glucose metabolism may be a biomarker of brain health, this decline in cerebral glucose metabolism, “may limit the brain(’s) ability to withstand neurodegenerative or cerebrovascular diseases in the future,” Gispert said in the press release.

Many older adults have been found to concurrently develop CVD and dementia, but few longitudinal studies have examined the role of atherosclerosis and its associated risk factors on brain health. This study, conducted in part with investigators from the University of Gothenburg, Sweden, also found that participants (many of whom were middle-aged) with worsening glucose metabolism had neuronal injury.

“Neuronal death is irreversible,” Cortés Canteli said.

Seeing middle-aged participants who had low glucose metabolism and presymptomatic atherosclerosis was revelatory, and this is why carotid screening could be so important, according to CNIC investigators. Having the ability to prevent CV decline and/or identify a patient’s risk of cerebral diseases or degradation could promote brain health in the long-term, according to the study authors.

“Although we still don’t know what impact this decline in cerebral metabolism has on cognitive function, the detection of neuronal injury in these individuals shows that the earlier we start to control cardiovascular risk factors, the better it will be for our brain,” Cortés Canteli said in the press release.


Early action to control cardiovascular risk factors preserves brain metabolism. Centro Nacional de Investigaciones Cardiovasculares. News Release. August 30, 2023. Accessed on August 31, 2023.

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