Men with risk factors for cardiovascular disease, including obesity, face a decline in brain health a decade earlier (from mid-50s to mid-70s) than women with similar consequences, who are most susceptible from mid-60s to mid-70s, suggest the findings of a long-term study. term study, published online in the Journal of Neurology Neurosurgery and psychiatry.
The most vulnerable parts of the brain are those involved in processing auditory information, aspects of visual perception, emotional processing and memory, with the damaging effects being just as evident in those carrying the high-risk APOE ε4 gene did not wear as those who did. show the findings.
It is clear that risk factors for cardiovascular disease, such as type 2 diabetes, obesity, high blood pressure and smoking, are associated with an increased risk of developing dementia.
But when is the best time to intervene with the right treatment to prevent the associated neurodegeneration, and whether this timing may differ between the sexes, is not clear, the researchers say.
To investigate this further, they called on 34,425 participants from the UK Biobank, all of whom had undergone abdominal and brain scans. Their average age was 63 years, but ranged from 45 to 82 years.
Cardiovascular disease risk was assessed using the Framingham Risk Score, which is based on: age; blood fats; systolic blood pressure-;the maximum arterial pressure exerted when the heart contracts and pumps blood, and represented by the first higher number in a measurement-;blood pressure medications; smoking; and diabetes.
In addition, changes in brain structure and volume were recorded using a neuroimaging technique called Voxel-based morphometry (VBM) to identify the influence of cardiovascular risk, abdominal fat and the fat surrounding body organs (visceral adipose tissue) on brain neurodegeneration .
Analysis of the data showed that higher levels of abdominal fat and visceral adipose tissue were associated with lower gray matter volume in the brain in both men and women.
The strongest impact of cardiovascular risk and obesity on brain neurodegeneration occurred a decade earlier in men than in women and lasted for 20 years, the data show. The effects were also stronger in men than in women.
Men were most susceptible to the harmful effects between the ages of 55 and 74, while women were most susceptible between the ages of 65 and 74.
High cardiovascular risk and obesity with a predisposition to gradual loss of brain volume over decades, occurring in a bell-shaped curve over time, with lower susceptibility at younger (under 55) and older ages (75+), although there were relatively few participants of either gender in these age groups, the researchers note.
Importantly, the associations persisted regardless of whether or not those affected carried the high-risk APOE ε4 gene.
The most vulnerable parts of the brain were the temporal lobes, located in the cerebral cortex, the outer surface of the brain. These regions are involved in the processing of auditory, visual and emotional information, and memory regions are affected early in the development of dementia.
“The deleterious impact of cardiovascular risk was widespread across cortical regions, highlighting how cardiovascular risk can affect a range of cognitive functions,” the researchers note.
“Therefore, modifiable cardiovascular risk factors, including obesity, deserve special attention in the treatment/prevention of neurodegenerative diseases, including Alzheimer’s disease,” they add.
“This underlines the importance of aggressively targeting cardiovascular risk factors before age 55 to prevent neurodegeneration and Alzheimer’s disease, in addition to the benefit of preventing other cardiovascular events, such as myocardial infarction. [heart attack] and stroke,” they point out.
“One such opportunity could be to repurpose agents used for obesity and type 2 diabetes mellitus for the treatment of Alzheimer’s disease,” they suggest, adding that other drugs used to treat cardiovascular and vascular diseases have also shown promise.
This is an observational study, so no firm conclusions can be drawn about cause and effect. And the researchers acknowledge several limitations to their findings, including that the UK Biobank has not recorded specific biomarkers for Alzheimer’s disease.
Atrophy of frontal, parietal and temporal brain areas is also typical of normal aging, making it difficult to precisely distinguish between the impact of cardiovascular risk on general aging processes and the risk of specific neurodegenerative disorders, they add.
But there are plausible biological explanations for the observed neuronal damage, they explain. These include inflammation, central leptin and insulin resistance, as well as the breakdown of the blood-brain barrier.
And they conclude: “Targeting cardiovascular risk and obesity a decade earlier in men than in women may be critical for potential candidates to gain a therapeutic benefit in preventing neurodegeneration and cognitive decline.”
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Magazine reference:
Cardiovascular risk and obesity are more likely to influence gray matter volume loss in men than in women. Journal of Neurology Neurosurgery and psychiatry. DOI: 10.1136/jnnp-2024-333675