At AAIC 2015, Steen Hasselbalch, M.D., and colleagues from the Danish Dementia Research Centre (DDRC), Copenhagen, Denmark reported results from the Danish ADEX Study, the first large, controlled trial of moderate to high intensity exercise in people with mild to moderate Alzheimer's in Denmark.

In the ADEX study, 200 people with Alzheimer's age 50-90 (average age 70.9 years) were randomly assigned to either a supervised aerobic exercise program (60-minute exercise sessions three times a week for 16 weeks supervised by experienced physiotherapists) or a control group (standard care, no extra exercise). In the exercise group, after 4 weeks of adaptation exercise, participants performed aerobic exercise at a target intensity of 70-80% of maximum heart rate for the remaining 12 weeks.

The researchers studied the effects of exercise on a range of factors related to Alzheimer's disease. The primary outcome measure was change from baseline to 16 weeks in cognitive performance estimated by Symbol-Digit Modalities test (SDMT). Secondary outcomes were neuropsychiatric and depressive symptoms, activities of daily living, quality of life and other cognitive measures. No significant difference was found between the intervention and control group on the primary outcome, but there was a significant difference in neuropsychiatric symptoms in favor of the intervention group (p=0.002).

At AAIC 2015, the researchers reported that:

• People who participated in the exercise program had far fewer neuropsychiatric symptoms (such as anxiety, irritability, and depression). Those in the control group had deteriorated on measures of psychiatric symptoms, while the intervention group improved slightly. This lead to a statistically significant difference between the two groups.
• People in a subgroup of the exercise group who attended more than 80% of the classes and exercised vigorously (raising their heart rate to more than 70% of their maximal rate) had statistically significant (p=0.03) improvements on mental speed and attention, as measured by the SDMT.
• People who participated in the exercise program improved in physical fitness, physical function, dual-task performance and exercise self-efficacy.

"Symptoms such as anxiety, irritability, and depression that often occur in Alzheimer's disease are the cause of great distress in both caregivers and people with the disease," Hasselbalch said. "While our results need to be verified in larger and more diverse groups, the positive effects of exercise on these symptoms that we saw in our study may prove to be an effective complement or combination with antidementia drugs. This calls for further study of multimodal treatment strategies, including lifestyle and drug therapies."

The Danish ADEX study was a collaboration between the DDRC, eight memory clinics in Denmark, and the Musculoskeletal Rehabilitation Research Unit, Bispebjerg & Frederiksberg Hospitals, University of Copenhagen.

One of the hallmarks of Alzheimer's is a brain lesion known as a tau tangle. Normally, tau functions to stabilize the structure of cells in the brain. When is becomes abnormal, tau initiates a variety of biological changes that can result in brain cells dying. Higher levels of tau in the brain are associated with faster rates of decline to Alzheimer's dementia. Therapies to prevent cognitive decline and dementia are now beginning to focus on reducing tau.

Researchers Laura Baker, Ph.D. and colleagues from Wake Forest Baptist Medical Center, Winston Salem NC, USA had previously shown that in older adults with mild cognitive impairment (MCI), regular moderate-to-high intensity aerobic exercise has benefits for cognition and plasma levels of amyloid protein, the primary component of the other Alzheimer's hallmark lesion, known as plaques. At AAIC 2015, they reported results of a 6-month randomized controlled trial of moderate-to-high intensity aerobic exercise in 65 sedentary adults 55-89 years old with MCI to test whether aerobic exercise might also lower tau levels in the brain.

Participants in the study were randomly assigned to either supervised aerobic training or a stretching group for 45-60 minutes four times per week for six months, using community facilities. The aerobic group exercised at 70-80% of their maximum heart rate, while the stretching group exercised at below 35 percent. The researchers tested participant's cognitive skills (verbal recall, tests of executive function) and examined blood and cerebrospinal fluid (CSF) samples at the beginning and end of the study. Forty participants also received MRI brain scans. Participants completed their assigned exercise activities 92 percent of the time.

The researchers found that:

• Participants who completed aerobic exercise (most commonly using a treadmill) saw a statistically significant (p<0.05) reduction in tau levels in CSF. The effect was most pronounced in adults over the age of 70.
• Aerobic exercise significantly (p<0.05) increased blood flow in the memory and processing centers of participant's brains, with a corresponding improvement in attention, planning, and organizing abilities referred to as "executive function" (p<0.05).

"These findings are important because they strongly suggest a potent lifestyle intervention such as aerobic exercise can impact Alzheimer's-related changes in the brain," Baker said. "No currently approved medication can rival these effects."

Cerebrovascular disease is the second most common cause of dementia in older adults, behind Alzheimer's. Research suggests that reducing heart health risk factors, such as high blood pressure and high cholesterol, may reduce dementia risk, and possibly even slow down the progression of cognitive decline due to mini-strokes – known as vascular cognitive impairment (VCI).

"This made us believe that aerobic exercise, such as running and brisk walking, may be a very promising strategy against vascular cognitive impairment," said Teresa Liu-Ambrose, Canada Research Chair, Ph.D., PT, University of British Columbia and researcher at the Djavad Mowafaghian Centre for Brain Health, which is part of the Vancouver Coastal Health Research Institute, Vancouver, BC, Canada. "Research shows that aerobic exercise not only decreases heart health risk factors but may also improve brain structure and function."

At AAIC 2015, Liu-Ambrose and colleagues reported results from a six-month study of 71 adults 56-96 years old with confirmed cases of mild VCI. Participants were assigned to two groups: one did supervised aerobic exercise three times per week for 60 minutes with certified fitness instructors, the other group received usual care plus an education seminar on nutrition once per month. All received the ADAS-Cog, a standard test of memory and thinking, at the beginning and end of the study.

Sixty-two of the 71 participants completed the full six-month study. The researchers found that study participants who took the aerobics classes significantly (p<0.05) improved their cognitive function, including memory and selective attention, compared to the people receiving usual care. In addition, functional brain scans acquired before and after the six-month study showed that the brains of study participants became more efficient with aerobic exercise training.

"While these promising results need to be replicated in larger and more diverse populations, the fact that aerobic exercise can improve cognitive function in VCI means that people with the condition have hope there may soon be a proven tool they can use to prolong their independence and improve their quality of life," said Liu-Ambrose. "Exercise is a strategy that can be inexpensively delivered at the population level."