Cardiovascular disease risk linked to early brain decline in men

The most vulnerable regions of the brain are those involved in processing auditory information, aspects of visual perception, emotional processing and memory, with the damaging effects just as evident in those who didn't carry the high risk APOE ε4 gene as those who did, the findings show.

But when might be the best time to intervene with appropriate treatment to stave off the associated neurodegeneration, and whether this timing might differ between the sexes, isn't clear, say the researchers.

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 reading-;blood pressure medication; smoking; and diabetes.

Additionally, 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 that surrounds body organs (visceral adipose tissue) on brain neurodegeneration.

The strongest influence of cardiovascular risk and obesity on brain neurodegeneration occurred a decade earlier in men than in women and was sustained over two decades, the data revealed. The effects were also stronger in men than they were in women.

Men were most susceptible to the damaging effects between the ages of 55 and 74, while women were most susceptible between the ages of 65 and 74.

Importantly, the associations remained, irrespective of whether or not those affected were carriers of the high risk APOE ε4 gene.

"This highlights the importance of aggressively targeting cardiovascular risk factors before the age of 55 years 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 emphasise.

"One such possibility may be in the repurposing of agents used for obesity and type 2 diabetes mellitus for the treatment of Alzheimer's disease," they suggest, adding that other drugs used for the treatment of cardiovascular disease have also shown promise.

This is an observational study, so no firm conclusions can be drawn about cause and effect. And the researchers acknowledge various limitations to their findings, including that the UK Biobank didn't record specific biomarkers for Alzheimer's disease.

Atrophy of frontal, parietal, and temporal brain regions is also typical of normal ageing, making it difficult to precisely differentiate between the impact of cardiovascular risk on general ageing processes and the risk of specific neurodegenerative conditions, 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 males than females may be imperative for potential candidates to achieve a therapeutic benefit in preventing neurodegeneration and cognitive decline."

Source:

BMJ Group

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