New research, published this week in Neurology, confirms that remaining physically and mentally stimulated helps to stave off cognitive decline. However, the underlying brain alterations involved in Alzheimer’s disease do not seem be affected in most individuals.

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Alzheimer’s disease progression appears to be more difficult to slow than previously thought.

Over the past few years, evidence has mounted that keeping your mind and body in motion through mid-life and into old age helps keep the brain nimble.

So far, evidence for the role of continued mental activity on Alzheimer’s pathology is not so well documented.

Efforts have been made to ascertain whether lifestyle enrichment minimizes the neurological changes that go hand in hand with Alzheimer’s. The results, so far, have not been definitive.

To date, most of these studies have been cross-sectional. In other words, the studies have not followed the patients as the brain ages, rather, they have dipped into a cross-section of the population at just one point in time.

This makes solid conclusions difficult to draw, because the progression within each individual is not charted.

Research, conducted at the Mayo Clinic in Rochester, MN, sets out to bridge some of these gaps. The team investigated the effects of a number of lifestyle and genetic parameters on the underlying pathophysiology of Alzheimer’s disease over time.

The team, led by Prashanthi Vemuri, used participants from the Mayo Clinic Study of Aging (MCSA). This sample consisted of 393 individuals, all over the age of 70. Of these, 340 were clinically normal and 53 had mild cognitive impairment.

The participants’ brains were measured for a number of Alzheimer’s-specific parameters. Firstly, cerebral amyloidosis was measured; this is the buildup of protein plaques in the brain that are a hallmark of Alzheimer’s disease.

Metabolism of glucose within the brain was also measured, as – in Alzheimer’s – this slows as the disease progresses. Finally, the researchers measured the volume of the hippocampus, an area of the brain involved in memory storage and emotion known to shrink during Alzheimer’s progression.

The volunteers received weekly questionnaires to evaluate levels of mental and physical activity.

The participants were split into two groups – high and low education. The high education group had 14 years of education or more and the low education group had under 14 years of education.

Apolipoprotein E (APOE) is a protein involved in cholesterol metabolism. Importantly, APOE4, a variant of APOE, is the largest known genetic risk factor for Alzheimer’s.

In a previous study, carriers of two APOE4 alleles were shown to have between 10 and 30 times the risk of developing Alzheimer’s by the age of 75, when compared with those without any APOE4 alleles. For this reason, the researchers also investigated the role of APOE on the neurological outcomes.

The current study found that APOE4 played a significant role in the way that mental and physical activity impacted Alzheimer’s etiology. Individuals in the higher education group who carried the APOE4 gene and continued to be mentally active had significantly fewer amyloid plaques than similarly educated individuals carrying the APOE4 gene who had not maintained mental stimulation throughout their lives.

Vemuri said of the results:

When we looked specifically at the level of lifetime learning, we found that carriers of the APOE4 gene who had higher education and continued to learn through middle age had fewer amyloid deposition on imaging when compared to those who did not continue with intellectual activity in middle age.”

However, for the group as a whole, mental and physical activity, occupation and education had no significant effect on amyloid plaques, glucose metabolism or hippocampus volume.

So, for the 20% of the population who carry the APOE4 gene, higher education and continued mental activity does seem to stave off some of the negative brain changes in Alzheimer’s disease; for the rest of the population, this does not appear to be the case.

The authors recognize that the current study has limitations. For instance, Vemuri says that “it is possible those who did not continue intellectual activity in middle age did so because they had higher levels of amyloid plaques.” The team ends the paper with a call for further research on a wider scale.

Medical News Today recently covered research that investigated a newly evolved human gene that prevents Alzheimer’s.