A long-term study by researchers at the Imperial College London and Cardiff University suggests that men with cardiovascular disease (CVD) risk factors, including obesity, face cognitive decline as early as a decade before similarly affected women. The research, which analyzed data from 34,425 UK Biobank participants, found that men begin to experience significant brain health deterioration from their mid-50s to mid-70s, while women are most vulnerable from their mid-60s to mid-70s.
The study, published online in the Journal of Neurology, Neurosurgery & Psychiatry, examined the impact of CVD risk factors such as high blood pressure, type 2 diabetes, obesity, smoking, and elevated blood fats on brain structure and function.
The most affected regions of the brain were those involved in memory, emotional processing, and visual and auditory perception. Further, the damaging effects of this decline are just as evident in those who didn’t carry the high-risk gene, APOE ε4, for developing Alzheimer’s disease as those who did. This finding suggests that the impact of cardiovascular disease on brain health could be independent of genetic predisposition.
“The detrimental impact of cardiovascular risk was widespread throughout cortical regions, highlighting how cardiovascular risk can impair a range of cognitive functions,” the researchers wrote.
For this research, the cardiovascular disease risk was assessed via the Framingham Risk Score, a sex-specific algorithm used to estimate the 10-year cardiovascular risk of an individual. The risk score takes into various data points including age, systolic blood pressure, blood fats, blood pressure medication, smoking, and diabetes. Changes in participants’ brain structure and volume were measured by Voxel-based morphometry, a computational neuroanatomy measurement of local concentrations of brain tissue. This allowed the investigators to pinpoint the influence of cardiovascular risk, abdominal fat, and visceral adipose tissue on brain neurodegeneration.
The analysis revealed that higher levels of both abdominal fat and visceral adipose tissue were associated with lower brain grey matter volume in both men and women, but that the strongest influence of cardiovascular risk and obesity on neurodegeneration risk presented a full decade earlier in men than in women and lasted 20 years. These effects were also more pronounced in men than in women.
“Targeting cardiovascular risk and obesity a decade earlier in males than females may be imperative for potential candidates to achieve a therapeutic benefit in preventing neurodegeneration and cognitive decline,” the study’s authors wrote.
The data show that high cardiovascular disease risk and high levels of body fat predisposed people to gradual loss of brain volume that occurs over several decade and occurs in a bell-shaped curve with susceptibility lower at age 55 and at ages over 75, although the researchers noted that there were few participants in the study representing these age groups.
The temporal lobes of the brain, located in the cerebral cortex, were the most vulnerable regions in the brain. These regions play an important role in aural, visual, and emotional information processing and are regions that are affected early in the development of dementia.
“The detrimental impact of cardiovascular risk was widespread throughout cortical regions, highlighting how cardiovascular risk can impair a range of cognitive functions,” the researchers said. “Therefore, modifiable cardiovascular risk factors, including obesity, deserve special attention in the treatment/prevention of neurodegenerative diseases, including Alzheimer’s disease.”
One potential intervention, beyond aggressive cardiovascular disease prevention strategies, could be to repurpose current medications that are used to treat obesity and type 2 diabetes for Alzheimer’s disease. Other drugs for cardiovascular disease also have potential.
While the study presents compelling evidence of these associations, it was an observational study, so no firm conclusions can be made about cause and effect. The researchers acknowledged that it is difficult to separate the effects of cardiovascular risk factors from the natural aging process, especially since brain atrophy in areas such as the frontal and temporal lobes is also typical of normal aging. However, the study shows there are plausible biological explanation for the observed damage, which included central leptin and insulin resistance, and the breakdown of the blood-brain barrier.
