By Michiel R.M. Twiss @physiotwiss
Regular aerobic exercise (AE) can stop and even reverse brain atrophy. One year of moderate AE has been shown to increase hippocampal volume and improve memory in healthy older adults (1). Recent meta-analytic evidence has confirmed the effects of AE at augmenting hippocampal volume in the healthy late adulthood brain (2,3). Furthermore, grey matter volume in older adults can benefit from physical activity (PA) and physical fitness (PF) and there may be a positive relationship between PA and white matter volume (4,5). It is not yet clear if brain volume augmentation is also mediated through resistance training (RT). RT may have benefits for human brain health, at least according to rodent studies (6,7). The previously mentioned review by Feter et al (2) reports on one study, in which AE (15 minutes) in combination with RT (30 minutes) was able to increase brain volume in obese individuals (8). However, no evidence was found for RT mediated increases in hippocampal volume in elderly women (9,10).
Exerceuticals versus pharmaceuticals for neurocognitive disorders
Performing intensive exercise (EX) over a long period of time improves PF in patients with dementia (11). Indeed, PA and its subset EX both have beneficial effects among people with pathological conditions, such as dementia, Parkinson’s disease (PD), multiple sclerosis (MS), depression and brain injury following e.g. trauma or stroke (12). These pathological conditions are associated with neurocognitive disorders (13) and cognitive impairment is common in the abovementioned conditions (14–16). Benefits of pharmacological treatment for cognitive impairment associated with these mentioned disorders are rather small (17,18). For example, among the many anti-dementia drugs, the apparent best drug is Donepezil (19) and a recent Cochrane review shows that patients with Alzheimer’s disease (AD) and treated with Donepezil ‘experience small benefits in cognitive function, activities of daily living and clinician‐rated global clinical state’ (20). PA and EX may have better treatment effects for cognitive impairment in patients suffering from dementia compared to pharmaceutical therapy, despite its role in improving cognition is still uncertain (21).
Exercise medicine for cognition in dementia
The positive effects of physical activity and exercise on cognition and brain function has been documented over the recent years (22). According to Schmid et al. (23) physiotherapeutic PAI can promote health in dementia and delay the course of the disease. A Cochrane review concludes that exercise programs may improve the ability to perform Activities of Daily Living (ADLs) in people with dementia’, but there is ‘no evidence of benefit from exercise on cognition, neuropsychiatric symptoms, or depression’ (24). However, more recent meta-analyses conclude that PAI such as AE and a combination of physical and cognitive training can benefit cognition in patients with dementia (25,26). Reasons for these conflicting conclusions are due to the way the (meta-)analyses were performed and heterogeneity (variation or differences across studies) was handled (27).
Exercise prescription for cognition in dementia
Recommendations for exercise prescription to stabilize and/or enhance cognitive function in patients with dementia can be made. For example, AE as in treadmill training for three months, twice a week for 30 minutes at 60% VO2max improved cognition as measured by the Cambridge Cognitive Examination (28).
Also nine weeks of combined AE and RT proved to be more effective than aerobic-only training in slowing cognitive decline in patients with dementia. AE consisted of twice weekly 30-minute walking sessions at moderate or high intensity as measured by rate of perceived exertion (RPE). Moderate and high intensity, i.e. at RPE 12 & 15 respectively, were adjusted by varying the individual walking distances per session. RT was executed twice weekly for half an hour and consisted of lower extremity exercises at RPE <12. The exercises were progressively loaded in frequency (three sets with 8-12 repetitions) and load via ankle weights (0.5-1.5 kgs).
Type of exercises: seated knee extension, plantar flexion through heel raises while holding both hands of the trainer, hip abduction by moving the straight leg sideways while standing behind and holding on to a chair, and hip extension by moving the straight leg backwards while standing behind and holding on to a chair (29). Despite these positive results, no benefits for cognition for combined AE and RT was observed in the Dementia and Physical Activity (DAPA) trial. On the Alzheimer’s Disease Assessment Scale ‐ Cognitive Subscale (ADAS‐Cog) the authors found a ‘small, statistically significant negative treatment effect’ (30). Interestingly, another novel treatment method that may improve cognition is intermittent hypoxic-hyperoxic training or IHHT. IHHT is a modified intermittent hypoxic training (IHT) and a noninvasive, easily applicable method based on repeated resting exposures to an oxygen-deficient gas mixture interspersed by normoxic periods. In a randomized controlled trial, IHHT contributed significantly to improvements in cognitive function in geriatric patients who suffered from moderate dementia (31).
Promotion of physical activity interventions to improve the health of patients suffering from dementia seems meaningful. Increasing evidence demonstrates the positive effects of PA – especially its subset EX – on brains of healthy and demented persons. In light of these findings and the modest effects of pharmaceutical treatment on cognitive functioning in the diseased brain, EX should be considered an important adjunct treatment. It remains unclear which EX and or training components are superior, i.e. show the largest beneficial effects. Further primary intervention research and subsequent systematic reviews with network meta-analyses may answer this important question.
Michiel R.M. Twiss @physiotwiss is a Dutch physiotherapist in Buchs SG, Switzerland. He has a keen interest in exercise medicine, gerontology research and strength and conditioning training in old age. He holds a private practice in Buchs, Sankt Gallen, Switzerland. Website: www.twiss-therapie.ch Email: firstname.lastname@example.org
- Erickson KI, Voss MW, Prakash RS, Basak C, Szabo A, Chaddock L, et al. Exercise training increases size of hippocampus and improves memory. Proc Natl Acad Sci. 2011 Feb 15;108(7):3017–22.
- Feter N, Penny JC, Freitas MP, Rombaldi AJ. Effect of physical exercise on hippocampal volume in adults: Systematic review and meta-analysis. Sci Sports [Internet]. 2018 Apr [cited 2018 Nov 4]; Available from: https://linkinghub.elsevier.com/retrieve/pii/S0765159718301539
- Firth J, Stubbs B, Vancampfort D, Schuch F, Lagopoulos J, Rosenbaum S, et al. Effect of aerobic exercise on hippocampal volume in humans: A systematic review and meta-analysis. NeuroImage. 2018 Feb;166:230–8.
- Erickson KI, Leckie RL, Weinstein AM. Physical activity, fitness, and gray matter volume. Neurobiol Aging. 2014 Sep;35 Suppl 2:S20-28.
- Sexton CE, Betts JF, Demnitz N, Dawes H, Ebmeier KP, Johansen-Berg H. A systematic review of MRI studies examining the relationship between physical fitness and activity and the white matter of the ageing brain. NeuroImage. 2016 01;131:81–90.
- Cassilhas RC, Lee KS, Fernandes J, Oliveira MGM, Tufik S, Meeusen R, et al. Spatial memory is improved by aerobic and resistance exercise through divergent molecular mechanisms. Neuroscience. 2012 Jan 27;202:309–17.
- Kelty TJ, Schachtman TR, Mao X, Grigsby KB, Childs TE, Olver TD, et al. Resistance-exercise training ameliorates LPS-induced cognitive impairment concurrent with molecular signaling changes in the rat dentate gyrus. J Appl Physiol Bethesda Md 1985. 2019 Jul 1;127(1):254–63.
- Mueller K, Möller HE, Horstmann A, Busse F, Lepsien J, Blüher M, et al. Physical exercise in overweight to obese individuals induces metabolic- and neurotrophic-related structural brain plasticity. Front Hum Neurosci. 2015;9:372.
- Best JR, Chiu BK, Liang Hsu C, Nagamatsu LS, Liu-Ambrose T. Long-Term Effects of Resistance Exercise Training on Cognition and Brain Volume in Older Women: Results from a Randomized Controlled Trial. J Int Neuropsychol Soc JINS. 2015 Nov;21(10):745–56.
- ten Brinke LF, Bolandzadeh N, Nagamatsu LS, Hsu CL, Davis JC, Miran-Khan K, et al. Aerobic exercise increases hippocampal volume in older women with probable mild cognitive impairment: a 6-month randomised controlled trial. Br J Sports Med. 2015 Feb;49(4):248–54.
- Pitkälä K, Savikko N, Poysti M, Strandberg T, Laakkonen M-L. Efficacy of physical exercise intervention on mobility and physical functioning in older people with dementia: a systematic review. Exp Gerontol. 2013 Jan;48(1):85–93.
- Professional Associations for Physical Activity, Swedish National Instituteof Public Health. Physical activity in the prevention and treatment of disease [Internet]. Östersund, Sweden: Swedish National Institute of Public Health; 2010 [cited 2017 Jul 7]. Available from: http://www.svenskidrottsmedicin.se/fyss/fyss_2010_english.pdf
- Neurocognitive disorder: MedlinePlus Medical Encyclopedia [Internet]. [cited 2019 Sep 20]. Available from: https://medlineplus.gov/ency/article/001401.htm
- Cumming TB, Marshall RS, Lazar RM. Stroke, cognitive deficits, and rehabilitation: still an incomplete picture. Int J Stroke Off J Int Stroke Soc. 2013 Jan;8(1):38–45.
- Kehagia AA, Barker RA, Robbins TW. Cognitive impairment in Parkinson’s disease: the dual syndrome hypothesis. Neurodegener Dis. 2013;11(2):79–92.
- Lovera J, Kovner B. Cognitive impairment in multiple sclerosis. Curr Neurol Neurosci Rep. 2012 Oct;12(5):618–27.
- Cicerone K, Levin H, Malec J, Stuss D, Whyte J. Cognitive rehabilitation interventions for executive function: moving from bench to bedside in patients with traumatic brain injury. J Cogn Neurosci. 2006 Jul;18(7):1212–22.
- Espay AJ, Dwivedi AK, Payne M, Gaines L, Vaughan JE, Maddux BN, et al. Methylphenidate for gait impairment in Parkinson disease: a randomized clinical trial. Neurology. 2011 Apr 5;76(14):1256–62.
- Cui C-C, Sun Y, Wang X-Y, Zhang Y, Xing Y. The effect of anti-dementia drugs on Alzheimer disease-induced cognitive impairment: A network meta-analysis. Medicine (Baltimore). 2019 Jul;98(27):e16091.
- Donepezil for dementia due to Alzheimer’s disease – Birks, JS – 2018 | Cochrane Library [Internet]. [cited 2019 May 11]. Available from: https://www.cochranelibrary.com/cdsr/doi/10.1002/14651858.CD001190.pub3/full
- Livingston G, Sommerlad A, Orgeta V, Costafreda SG, Huntley J, Ames D, et al. Dementia prevention, intervention, and care. Lancet Lond Engl. 2017 Dec 16;390(10113):2673–734.
- Hillman CH, Erickson KI, Kramer AF. Be smart, exercise your heart: exercise effects on brain and cognition. Nat Rev Neurosci. 2008 Jan;9(1):58–65.
- Schmid C, Gebhard D, Fluch E, Mitterbacher A, Mir E, Bokalic M, et al. Physiotherapeutische Bewegungsinterventionen zur Gesundheitsförderung bei Demenz. physioscience. 2015 Dec 1;11(04):134–40.
- Forbes D, Forbes SC, Blake CM, Thiessen EJ, Forbes S. Exercise programs for people with dementia. Cochrane Database Syst Rev [Internet]. 2015 [cited 2019 Oct 1];(4). Available from: https://www.cochranelibrary.com/cdsr/doi/10.1002/14651858.CD006489.pub4/full
- Groot C, Hooghiemstra AM, Raijmakers PGHM, van Berckel BNM, Scheltens P, Scherder EJA, et al. The effect of physical activity on cognitive function in patients with dementia: A meta-analysis of randomized control trials. Ageing Res Rev. 2016 Jan;25:13–23.
- Karssemeijer EGA, Aaronson JA, Bossers WJ, Smits T, Olde Rikkert MGM, Kessels RPC. Positive effects of combined cognitive and physical exercise training on cognitive function in older adults with mild cognitive impairment or dementia: A meta-analysis. Ageing Res Rev. 2017;40:75–83.
- Straus S, Watt J. Aerobic and strength training did not improve cognitive function in mild to moderate dementia. Ann Intern Med. 2018 18;169(6):JC34.
- Arcoverde C, Deslandes A, Moraes H, Almeida C, Araujo NB de, Vasques PE, et al. Treadmill training as an augmentation treatment for Alzheimer’s disease: a pilot randomized controlled study. Arq Neuropsiquiatr. 2014;72(3):190–6.
- Bossers WJR, van der Woude LHV, Boersma F, Hortobágyi T, Scherder EJA, van Heuvelen MJG. A 9-Week Aerobic and Strength Training Program Improves Cognitive and Motor Function in Patients with Dementia: A Randomized, Controlled Trial. Am J Geriatr Psychiatry Off J Am Assoc Geriatr Psychiatry. 2015 Nov;23(11):1106–16.
- Aerobic and strength training did not improve cognitive function in mild to moderate dementia | Cochrane Library [Internet]. [cited 2019 Oct 1]. Available from: https://www.cochranelibrary.com/central/doi/10.1002/central/CN-01649061/full?highlightAbstract=withdrawn%7Cdementia%7Cdementi%7Ctraining%7Cstrength%7Ctrain
- Bayer U, Likar R, Pinter G, Stettner H, Demschar S, Trummer B, et al. Intermittent hypoxic-hyperoxic training on cognitive performance in geriatric patients. Alzheimers Dement N Y N. 2017 Jan;3(1):114–22.