Alzheimer's: Can a challenging job and exercise keep the condition at bay?

Research teams from around the world are looking for ways to prevent dementia in old age. For people with Alzheimer's disease, such interventions are sorely needed; there are currently no reliable treatments to stop neurodegeneration.

The main hallmark of Alzheimer's disease is a progressive loss of brain matter that eventually leads to cognitive decline. Two proteins abnormally accumulate in and around neurons in the brains of people with Alzheimer's disease, causing cell death.

Drugs for the condition only treat the symptoms. Researchers are therefore looking at ways of halting or slowing down cognitive decline by boosting brain health before neurodegeneration occurs.

Research presented at the Alzheimer's Association International Conference (AAIC) 2017, held in London, United Kingdom, examined the link between lifestyle and cognitive decline.

The findings point toward occupation in early life and targeted interventions later in life as having a positive effect on cognition.

Complex occupations

A study by Allison Kaup, Ph.D., and colleagues from the University of California, San Francisco looked at the influence that the type of profession someone chooses in early and mid-adulthood has on cognitive decline in later life. The study commenced when participants were between the ages of 18 and 30, and it ran for 25 years.

Occupational complexity is a measure of how cognitively challenging a particular profession is. An example of a low-complexity job is a machine operator, while teachers are in the medium-complexity job group. High-complexity professions include engineering.

The team's data showed that occupational complexity in early life was associated with greater white matter integrity, meaning fewer signs of aging and higher processing speed and executive function in mid-life.

But it is not clear whether a more complex job causes these signs or white matter complexity influences career choice. It is also too early to tell whether the study participants are going to develop Alzheimer's disease over time, but the team will continue to monitor them.

A question raised by a member of the audience was whether or not individuals with complex jobs would benefit from any additional lifestyle interventions, such as brain training, but the jury is still out on this.

So what is the evidence of lifestyle interventions in Alzheimer's disease prevention?

Training the brain and the body

A study presented by Bianca Bier, Ph.D., from the University of Montreal in Canada, looked at the effects of two different types of brain training.

Single attention training allowed participants to focus on one of two tasks and practice it repeatedly. But in the divided attention training group, participants performed two different tasks at the same time, controlling which one they paid the most attention to.

In a study of 30 healthy adults, these two different training schemes had very different effects on the brain. For instance, divided attention training activated those regions of the brain responsible for multitasking, but this plateaued halfway through the study.

Meanwhile, single attention training resulted in rapid activation of regions responsible for the particular task the participants were performing up to the halfway study point, but it declined afterward.

Dr. Bier explained that this is important as it means that all brain training exercises are not equal, and that it will be important to choose the right type for individual patients.

This assessment was echoed by Narlon Silva, a Ph.D. student from Western University in Ontario, Canada, who looked at physical exercise and cognitive function.

His study included seniors who had all self-reported some cognitive decline. He compared regular mixed physical exercise - which consisted of aerobic and strength training - with an additional group that performed a new form of mind-motor training.

In this type of training, an instructor demonstrates a stepping pattern on a mat that is marked with four columns of equal squares. As the instructor moves along the mat, he places his feet on different squares, creating a stepping pattern that can range from simple to complex.

Participants were then asked to copy the stepping pattern demonstrated to them in an exercise lasting 15 minutes. These exercises were repeated three times per week for 24 weeks.

Both groups improved in their cognitive function after 24 weeks, but there was no difference between the groups.

However, during a subsequent follow-up at 52 weeks, the mind-motor training group had improved significantly more than the exercise-only group.

This led Silva to speculate that the training tested in the study had a delayed effect, and that, as Dr. Bier had found, all training is not equal.

The data presented at AAIC certainly point to exercise, cognitive training, and cognitive complexity in daily life as all having a positive influence in preventing decline in old age. But do scientists know anything about the underlying causes?

Genes and biomarkers

There is certainly an interest in the scientific community to establish the mechanisms by which lifestyle factors and interventions might protect us from neurodegeneration.

Shireen Sindi, Ph.D., from the Karolinska Institute in Stockholm, Sweden, presented data on the molecular basis of aging and lifestyle interventions, focusing on telomeres in particular.

Telomeres are short stretches of DNA at the ends of chromosomes that act as protective caps. When cells age, these telomere stretches shorten, eventually signaling to the cell that it is at the end of its lifespan.

The telomeres in a particular set of white blood cells, or leukocytes, are known to be biomarkers for biological age. Longer telomere length is thought to be associated with better cognition.

Dr. Sindi and colleagues assessed telomere length in a group of seniors who had received lifestyle interventions and compared this with a group who had not received any intervention.

The lifestyle interventions consisted of nutritional advice, supervised physical exercise, cognitive training, and monitoring for metabolic and vascular risk factors.

Although there was no change in telomere length over a 2-year period when the whole study group was assessed, there was an effect in those individuals carrying a mutation in one of the genes associated with higher risk of developing Alzheimer's.

In those individuals who had longer telomeres and had received the lifestyle intervention, this was associated with improvements in memory and executive functioning.

How this was caused is unclear from the study, but the team is continuing to investigate this phenomenon.

Andrea Rosso, Ph.D., an assistant professor at the University of Pittsburgh in Pennsylvania, meanwhile, set out to uncover why some people respond to physical exercise inventions better than others.

Her hunt for these super-responders saw her looking at genes involved in dopamine regulation. This neurotransmitter is known to regulate processes such as cognition control and motivation response.

Her study involved seniors across eight centers in the United States, none of whom had any major cognitive impairment. Half of these received a physical exercise intervention, which involved a mix of center visits and home-based training, with the aim of getting each participant to do 30 minutes of exercise per day. The study ran for 24 months, with a follow-up visit 12 months later.

One of the genes that Prof. Rosso looked at, called DRD2, showed some interesting effects in a subset of individuals in the intervention group.

The findings were only significant for white study participants, who showed that one particular variant of this gene was associated with higher exercise levels during the study period. However, regardless of which variant of the gene a particular participant carried, all had reverted back to pre-intervention exercise levels at the 12-month follow-up.

Prof. Rosso speculated that higher dopamine levels may play a role in sticking to exercise regimes in lifestyle interventions, but more work is needed.

Needless to say, understanding how lifestyle and targeted interventions affect the brain is complex. However, keeping the brain and body active throughout life certainly seems to have positive effects on brain health.

Meanwhile, scientists are continuing their search for the best methods to keep our brains young and protect them from the deadly neurodegeneration that occurs in Alzheimer's disease.