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  • One year aerobic exercise increases regional cerebral blood flow in anterior cingulate cortex: a blinded, randomized trial in patients with Mild Cognitive Impairment

    • B. P. THOMAS ;
    • T. TARUMI ;
    • M. SHENG ;
    • B. Y. TSENG ;
    • K. WOMACK ;
    • M. C. CULLUM ;
    • B. RYPMA ;
    • R. ZHANG ;
    • H. LU ;

    Information from abstracts and lay language summaries is embargoed until the conclusion of the scientific presentation.

    188—Novel Therapeutics for Neurodegenerative Disorders

    Sunday, November 12, 2017, 1:00 pm - 3:15 pm

    188.09 One year aerobic exercise increases regional cerebral blood flow in anterior cingulate cortex: a blinded, randomized trial in patients with Mild Cognitive Impairment

    Location: 146C

    *B. P. THOMAS1, T. TARUMI5, M. SHENG1, B. Y. TSENG5, K. WOMACK2, M. C. CULLUM3, B. RYPMA6, R. ZHANG5,4, H. LU7,1;
    1Advanced Imaging Res. Ctr., 2Dept. of Neurol. and Neurotherapeutic, 3Dept. of Psychiatry, 4Dept. of Intrnl. Med., Univ. of Texas Southwestern Med. Ctr., Dallas, TX; 5Inst. for Exercise and Envrn. Medicine, Texas Hlth. Presbyterian Hosp., Dallas, TX; 6Dept. of Behavioral and Brain Sci., Univ. of Texas at Dallas, Dallas, TX; 7Dept. of Radiology, Johns Hopkins Univ., Baltimore, MD

    Abstract Body: Individuals with mild cognitive impairment (MCI) are at an early stage of Alzheimer’s disease (AD), and have high risk of inevitable decline to AD. Much research has focused on preventing this decline, but negative outcomes from several AD clinical trials has led us to research other alternatives. Aerobic exercise may be effective at preventing AD. It is shown to improve cardiorespiratory and cognitive function in older adults with and without MCI. The mechanisms of cognitive function improvement are not well understood, and are the topic of this research. We hypothesized that aerobic exercise improves cerebrovascular function, which leads to brain function improvement. We used Pseudo-Continuous-Arterial-Spin-Labeling (PCASL) MRI to measure resting cerebral blood flow (CBF) in MCI. Non-aerobic stretching was used as control for comparison. 30 subjects with MCI were recruited and assigned to perform either aerobic exercise, or non-aerobic stretching for one year. Both groups were age, gender, education, BMI, and clinically matched. The aerobic exercise group was trained to maintain their heart rate (HR) within 55-65% of max HR during exercise. The stretch group performed upper and lower body stretching and maintained their HR below 55% of max HR. Both groups began training at 3 sessions per week, 30 minutes per session, and intensity was gradually increased. Resting CBF was measured in all subjects at the start and end of training in a 3T MRI scanner using a PCASL sequence. For each subject, the CBF map pre training was subtracted from that post training (Post-Pre), to obtain a difference map. CBF maps were then compared between groups to assess changes in CBF due to aerobic exercise compared to stretch (Exercise>Stretch). Cardiorespiratory fitness, was significantly higher (p<0.05) in the exercise group alone. Memory function as measured by the logical memory (LM) delayed recall test improved significantly in the aerobic exercise group alone. CBF increased in the exercise group compared to the stretch group in the anterior cingulate cortex (ACC), medial frontal gyrus (MFG, BA32) and inferior frontal gyrus. A voxel-wise regression analysis revealed that improvement in memory function correlated positively with CBF increase in the ACC and MFG (BA6). Chapman et al reported similar exercise induced CBF increase in the ACC in older adults. The ACC and MFG, represent a critical node in working memory, involved in monitoring of memory and allocation of attention supporting memory. In summary, aerobic exercise improved cardiovascular and cognitive function in MCI. Improvement in cognitive function was suggested to be mediated by increases in CBF in the ACC and frontal lobe.

    Lay Language Summary: Our research shows that aerobic exercise is capable of improving memory function in patients with amnestic Mild Cognitive Impairment (MCI), individuals who are at high risk for Alzheimer’s disease (AD). This improvement might occur because, as our data show, blood flow to the Anterior Cingulate Cortex (ACC) of the brain increases in association with aerobic exercise. This blood flow increase was related to the improvement in memory performance.
    In the US there are about 5.4 million people living with AD-related memory impairment, and 11% of the population over the age of 65 has AD, which strain patients, caregivers and the healthcare system. To develop effective treatment strategies, we must understand the pathophysiologic mechanisms of AD, especially at the MCI stage. 10% per year of those with MCI progress to AD.
    Much research has focused on preventing the onset of AD, but negative outcomes from several AD clinical trials has led us to explore alternative strategies. Aerobic exercise may be an effective approach for preventing AD. It is known to improve cardiorespiratory and cognitive function in older adults with and without MCI, although the mechanisms of cognitive improvement are not yet understood. We hypothesized that aerobic exercise improves brain vascular function, leading to brain function improvement.
    We used Magnetic Resonance Imaging (MRI) to non-invasively measure resting cerebral blood flow (CBF) in 30 patients with amnestic MCI. Fifteen participants were assigned to perform aerobic exercise and 15 were assigned to perform non-aerobic stretching. Both groups were age, gender, education and BMI matched and underwent training for one year. The aerobic exercise group was trained to maintain their heart rate (HR) within 60-70% of max HR during exercise. The stretch group performed upper and lower body stretching and maintained their HR below 50% of max HR. Both groups began training at 30 minutes per session, 3 sessions per week. Exercise frequency and duration was gradually increased to 4-5 sessions per week and 40-50 minutes per session over a period of 6 months and maintained at this level during the rest of the 6 month training period. Memory function was assessed using a standard paragraph recall task, and resting CBF was measured at the start and end of training using arterial spin labeling (ASL) MRI.
    After one year of training, cardiorespiratory fitness was found to be significantly improved in the exercise group, while the stretch group did not change. Delayed paragraph recall improved significantly in the aerobic exercise group, while the stretch group did not show improvement. CBF increased in the exercise group compared to the stretch group in the ACC, the medial frontal gyrus (MFG) and inferior frontal gyrus. Increase in CBF in the ACC is similar to previous studies that found aerobic exercise induced CBF increase in the ACC in cognitively normal older adults. It appears that ACC and MFG are involved in monitoring of memory and allocation of attention supporting memory. Improvement in memory function correlated positively with the regional increase in CBF in the ACC and MFG. These findings suggest that improvement in cognitive performance in MCI was associated with increases in CBF with aerobic exercise.
    In summary, this study is the first to measure CBF in MCI participants in response to aerobic exercise. Aerobic exercise improved cardiorespiratory and memory function in MCI and the improvement in memory performance may be attributed to an increase in CBF in the ACC. In our future work, we will assess the dilation capacity of blood vessels in these participants, which is an indicator of the elasticity of blood vessels. Improvement in vessel dilation capacity is also known to cause improvement in brain function.