Exercise may slow withering effects of Alzheimer’s

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Exercising several times a week may delay brain deterioration in people at high risk for Alzheimer’s disease, according to a proof of concept study.

Research from University of Texas Southwestern found that people who had accumulation of amyloid beta in the brain – a hallmark of Alzheimer’s disease – experienced slower degeneration in a region of the brain crucial for memory if they exercised regularly for one year.

Although exercise did not prevent the eventual spread of toxic amyloid plaques blamed for killing neurons in the brains of dementia patients, the findings suggest an intriguing possibility that aerobic workouts can at least slow down the effects of the disease if intervention occurs in the early stages.

“What are you supposed to do if you have amyloid clumping together in the brain? Right now doctors can’t prescribe anything,” said Dr Rong Zhang, who led the clinical trial that included 70 participants ages 55 and older. “If these findings can be replicated in a larger trial, then maybe one day doctors will be telling high-risk patients to start an exercise plan. In fact, there’s no harm in doing so now.”

The study compared cognitive function and brain volume between two groups of sedentary older adults with memory issues: One group did aerobic exercise (at least a half-hour workout four to five times weekly), and another group did only flexibility training.

Both groups maintained similar cognitive abilities during the trial in areas such as memory and problem solving. But brain imaging showed that people from the exercise group who had amyloid build-up experienced slightly less volume reduction in their hippocampus – a memory-related brain region that progressively deteriorates as dementia takes hold.

“It’s interesting that the brains of participants with amyloid responded more to the aerobic exercise than the others,” said Zhang, who conducted the trial at the Institute for Exercise and Environmental Medicine. “Although the interventions didn’t stop the hippocampus from getting smaller, even slowing down the rate of atrophy through exercise could be an exciting revelation.” However, Zhang notes that more research is needed to determine how or if the reduced atrophy rate benefits cognition.

The search for dementia therapies is becoming increasingly pressing: More than 5m Americans have Alzheimer’s disease, and the number is expected to triple by 2050. Recent research has helped scientists gain a greater understanding of the molecular genesis of the disease, including a UT Southwestern discovery published last year that is guiding efforts to detect the condition before symptoms arise. Yet the billions of dollars spent on trying to prevent or slow dementia have yielded no proven treatments that would make an early diagnosis actionable for patients.

Zhang is among a group of scientists across the world trying to determine if exercise may be the first such therapy. His latest research builds upon numerous studies suggesting links between fitness and brain health. For example, a 2018 study showed that people with lower fitness levels experienced faster deterioration of vital nerve fibres in the brain called white matter. Research in mice has similarly shown exercise correlated with slower deterioration of the hippocampus – findings that prompted Zhang to investigate whether the same effects could be found in people.

“I’m excited about the results, but only to a certain degree,” Zhang said. “This is a proof-of-concept study, and we can’t yet draw definitive conclusions.”

Zhang is leading a five-year national clinical trial that aims to dig deeper into potential correlations between exercise and dementia. The trial, which includes six medical centres across the country, involves more than 600 older adults (ages 60-85) at high risk of developing Alzheimer’s disease. The study will measure whether aerobic exercise and taking specific medications to reduce high blood pressure and cholesterol can help preserve brain volume and cognitive abilities.

“Understanding the molecular basis for Alzheimer’s disease is important,” Zhang said. “But the burning question in my field is, ‘Can we translate our growing knowledge of molecular biology into an effective treatment?’ We need to keep looking for answers.”

Abstract
Background: The current evidence is inconclusive to support the benefits of aerobic exercise training (AET) for preventing neurocognitive decline in patients with amnestic mild cognitive impairment (aMCI).
Objective: To examine the effect of a progressive, moderate-to-high intensity AET program on memory and executive function, brain volume, and cortical amyloid-β (Aβ) plaque deposition in aMCI patients.
Methods: This is a proof-of-concept trial that randomized 70 aMCI patients to 12 months of AET or stretching and toning (SAT, active control) interventions. Primary neuropsychological outcomes were assessed by using the California Verbal Learning Test-second edition (CVLT-II) and the Delis–Kaplan Executive Function System (D-KEFS). Secondary outcomes were the global and hippocampal brain volumes and the mean cortical and precuneus Aβ deposition.

Results: Baseline cognitive scores were similar between the groups. Memory and executive function performance improved over time but did not differ between the AET and SAT groups. Brain volume decreased and precuneus Aβ plaque deposition increased over time but did not differ between the groups. Cardiorespiratory fitness was significantly improved in the AET compared with SAT group. In amyloid positive patients, AET was associated with reduced hippocampal atrophy when compared with the SAT group.
Conclusion: The AET and SAT groups both showed evidence of slightly improved neuropsychological scores in previously sedentary aMCI patients. However, these interventions did not prevent brain atrophy or increases in cortical Aβ deposition over 12 months. In amyloid positive patients, AET reduced hippocampal atrophy when compared with the SAT group.

Authors
Takashi Tarumi, Heidi Rossetti, Binu P Thomas, Thomas Harris, Benjamin Y Tseng, Marcel Turner, Ciwen Wang, Zohre German, Kristin Martin-Cook, Ann M. Stowe, Kyle B Womack, Dana Mathews, Diana R Kerwin, Linda Hynan, Ramon Diaz-Arrastia, Hanzhang Lu, C Munro Cullum, Rong Zhang

UT Southwestern Medical Centre material Journal of Alzheimer’s Disease abstract

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