Physical Activity Improves Biomarkers of Autosomal Dominant Alzheimer’s Disease

by | May 6, 2019 | 2018, Aging, Alzheimer's Disease, Brain Health, Fitness and Exercise

Written by Joyce Smith, BS. Individuals with familial AD mutations who exercised more than 2.5 hours per week had significantly better cognitive and functional performance and significantly less AD-pathology in their cerebrospinal fluid than those who exercised less.

agingPrevious research suggests that physical activity may benefit healthy older people with mild cognitive impairment who are at risk of Alzheimer’s disease 1,2 and may even slow down the rate of neuropathological changes that accompany cognitive decline. 3  Autosomal dominant AD is a rare form of AD resulting in aggregation of the amyloid-b peptide into amyloid plaques due to alteration of amyloid-b processing. A small study by Brown et al, 2017, indicated that exercise slowed amyloid accumulation in presymptomatic AD mutation carriers who already had some amyloid in the brain. 4

To investigate further, Müller and colleagues, 5 using a cross-sectional design, analyzed accumulated data on the physical activity, cognitive performance, and biomarkers of amyloid load at baseline among 224 DIAN participants who carry familial AD mutations and 148 healthy, age-matched noncarriers. The carriers were divided into high physical activity (n=156) and low physical activity (n=68) groups with 2.5 hours per week as the cutoff. This was the amount recommended by the world Health Organization and was achieved by 40% of the mutation carriers. The high physical activity (PA) group was 4 years younger than the low physical activity (PA) group, thus further from their predicted disease onset. The carriers averaged 38 years old and included both asymptomatic and symptomatic volunteers. All participants (mutation carriers and noncarriers) reported the amount of time they spent over the preceding year on any of 10 different activities, including walking, cycling, or tennis. A family member or friend corroborated the self-reporting. Over 70% of mutation-carrier population achieved the recommended amount of at least 150 minutes of PA per week.

  • Mutation carriers who were closer to their expected age of disease onset had lower levels of physical activity.
  • Mutation carriers with high PA had significantly better cognitive and functional performance as indicated by Mini Mental State Examination (MMSE) and functional status (CDR-SOB) scores than mutant carriers with low PA.
  • In addition to a slowing of cognitive decline, the mutation carriers with high PA had less tau and Aβ pathology (based on modeled trajectories of CSF total tau and the total tau/Aβ1-42 ratio) than mutation carriers with low PA.  In fact, mutation carriers with a high PA scored 3.4 points better on MMSE at expected symptom onset, and fulfilled the diagnosis of very mild dementia 15.1 years later compared with low exercisers.
  • Exercise was not associated with cognitive scores in healthy noncarriers.

While this study offers compelling cross-sectional data on the relationship between physical activity, cognition, functional ability, and Alzheimer’s disease biomarkers in an autosomal-dominant AD population, it does not reflect the population as a whole, since fewer than 50% of adults in the United States obtain the recommended 150 minutes of physical activity per week. Also, the cross-sectional data do not prove cause and effect. Whether higher physical activity is the reason for better cognition, or if better cognition is associated with higher activity, the effect of exercise will require longitudinal data. In the DIAN study, many participants have by now accumulated five or more years of follow-up data, which can be used in a future longitudinal study. Improving on self-reported questionnaires and utilizing more inclusive neuropsychological testing to gauge cognitive and functional status would be beneficial as well. Nonetheless, these results do support a beneficial effect of physical exercise on cognition and dementia symptoms in individuals with genetically driven autosomal dominant AD.

Source: Müller, Stephan, Oliver Preische, Hamid R. Sohrabi, Susanne Gräber, Mathias Jucker, John M. Ringman, Ralph N. Martins et al. “Relationship between physical activity, cognition, and Alzheimer pathology in autosomal dominant Alzheimer’s disease.” Alzheimer’s & Dementia 14, no. 11 (2018): 1427-1437.

© 2018 the Alzheimer’s Association. Published by Elsevier Inc. All rights reserved.

Posted May 6, 2019.

Joyce Smith, BS, is a degreed laboratory technologist. She received her bachelor of arts with a major in Chemistry and a minor in Biology from  the University of Saskatchewan and her internship through the University of Saskatchewan College of Medicine and the Royal University Hospital in Saskatoon, Saskatchewan. She currently resides in Bloomingdale, IL.

References:

  1. Yu F, Vock DM, Barclay TR. Executive function: Responses to aerobic exercise in Alzheimer’s disease. Geriatric nursing (New York, NY). 2018;39(2):219-224.
  2. Ohman H, Savikko N, Strandberg TE, et al. Effects of Exercise on Cognition: The Finnish Alzheimer Disease Exercise Trial: A Randomized, Controlled Trial. J Am Geriatr Soc. 2016;64(4):731-738.
  3. Okonkwo OC, Schultz SA, Oh JM, et al. Physical activity attenuates age-related biomarker alterations in preclinical AD. Neurology. 2014;83(19):1753-1760.
  4. Brown BM, Sohrabi HR, Taddei K, et al. Habitual exercise levels are associated with cerebral amyloid load in presymptomatic autosomal dominant Alzheimer’s disease. Alzheimer’s & dementia : the journal of the Alzheimer’s Association. 2017;13(11):1197-1206.
  5. Muller S, Preische O, Sohrabi HR, et al. Relationship between physical activity, cognition, and Alzheimer pathology in autosomal dominant Alzheimer’s disease. Alzheimer’s & dementia : the journal of the Alzheimer’s Association. 2018;14(11):1427-1437.