Dementia has a profound decline in cognitive abilities which greatly impacts an individual’s capability to live independently. A 2019 estimate indicated that about 57.4 million individuals worldwide were living with dementia. This number is expected to increase to as much as 152 million in 2050.
Alzheimer’s disease accounts for 60-80% of dementia cases and is considered the primary cause of dementia worldwide(1).
There has been a huge effort in testing and
developing therapies for Alzheimer’s disease, but the failure rate is particularly high.
The lack of robust treatment approaches for Alzheimer’s disease has driven research into non-pharmacological interventions, such as physical activity, to slow cognitive-functional decline and potentially delay the onset of dementia.
Interest in this area are well-grounded, considering that at least 30–40 % of dementia cases are attributable to modifiable risk factors such as physical inactivity(2).
Structured physical activity comprises at least three fundamental types of exercise with distinct physiologic demands:
- – Aerobic exercise
- – Resistance exercise (aka strength training)
- – Coordinative exercise
Aerobic exercise such as brisk walking, jogging, swimming, and cycling involves a significant increase in oxygen consumption compared to resting levels, requiring energy expenditure to sustain an elevated heart rate and heightened oxygen intake(3).
Resistance exercise entails physical activities requiring muscular force against external resistance, such as weightlifting(4).
Coordinative exercise involves movements requiring sensory and neuromuscular control mechanisms to maintain body stability throughout each motion, including activities like gymnastics and
yoga.
Aerobic exercise has the most researched and has demonstrated significant brain and cognitive benefits. Although less well researched, convincing arguments suggest that resistance exercise may provide comparable benefits to aerobic exercise and there may be distinct mechanisms that confer them. This article will focus on the impact of resistance exercise on the brain.
Physical Activity and Cognitive Function
Research exploring the relationship between cognition and aerobic exercise has revealed that regular aerobic exercise, even at low intensity (e.g., walking), leads to increased cortical thickness and brain volume in critical brain regions like the prefrontal and temporal cortices, the hippocampus, and various gray and white matter regions in older healthy individuals(5).
Changes in brain structure or volume appear to correlate with enhanced cardiovascular fitness. Cerebral angiogenesis and improved vascularization are believed to underlie some of
Exercise-induced increases in brain-derived neurotrophic growth factors is another proposed mechanism facilitating the cognitive benefits of aerobic exercise.
Consequences of Normal Aging on Brain Structure
Many of the changes that occur during adulthood become apparent after reaching the age of around 55, though changes in functions such as executive function, memory, and processing speed can appear much earlier(6).
Gross brain volume decreases over time and by the time individuals reach 90 years of age, their average brain weight may have decreased by as much as 15% from its peak capacity(7).
Age-related brain atrophy coincides with a decline in specific cognitive functions.
Cognitive functions generally follow three patterns of age-related change:
- Decreasing across the lifespan
(e.g., processing speed and executive function)
- Decreasing in late life (e.g., numerical ability, spatial orientation, reasoning, mental set shifting, and inhibition)
- Remaining relatively stable or moderately increasing over time, as seen with crystallized intelligence
(e.g., semantic knowledge, emotional regulation and processing, and autobiographical and automatic memory), which typically remains intact well into a person’s sixth and seventh decades(6).
Importantly, while the typical age-related declines in cognitive function are less severe than those observed in dementing illnesses, they may still hinder one’s capability to execute tasks requiring flexible cognitive skills such as quick thinking, adaptability, logical reasoning, and the capacity to concentrate on specific tasks or multitask, as exemplified by activities like driving or managing air traffic control(8).
Impact of Resistance Exercise on Alzheimer’s Disease-Associated Brain Structures
Research demonstrates that following 52 weeks of resistance exercise (once or twice weekly), exhibited an unexpected decrease in brain volume compared to the control group, which showed no change. Interestingly, this reduced brain volume coincided with enhanced cognitive function, which was attributed to lower brain volumed having less pathological plaque burden. Subsequent neuroimaging analysis on those who engaged in resistance exercise twice a week displayed preserved cortical white matter volume further supporting the resistance exercise dose-response hypothesis(9).
Another study showed that following 12 months of resistance exercise; twice a week, but not once a week, reduced the progression of white matter lesions(10).
Recent findings identified several significant observations:
- – At six months, increased posterior cingulate cortical thickness was observed in study participants assigned to the resistance exercise group. In addition, greater hippocampal network connectivity was evident(11).
- – Resistance exercise participants who displayed the greatest increases in posterior cingulate cortical thickness post-intervention had less subiculum and dentate gyrus atrophy at 18 months.
- – Functional neuroimaging revealed strengthened connectivity between the posterior cingulate and the hippocampus, to which they proposed that the preservation of these hippocampal subfields results from upregulated hippocampal- posterior cingulate functional connectivity — a change previously identified as unique to resistance exercise(12).
At this point, the critical question is whether these
changes in brain structure align with cognitive function, and whether resistance exercise-driven changes in structure mitigate the risk of Alzheimer’s disease-dementia.
The collective findings from the research to date allow for several hypotheses:
- –
Firstly, that resistance exercise follows a dose-response effect, whereby significant benefits on the brain manifest following a consistent resistance exercise regimen lasting at least 6 months and involving a minimum of two weekly sessions. Such benefits may last for months or even years after discontinuation of resistance exercise(11).
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Secondly, that the outcomes of resistance exercise could be influenced by modifiers like sex, education level, and other inter-individual differences such as genetic risks and baseline health. For instance, the Brain Power study, which exclusively involved healthy women, observed cognitive benefits only after 12 months of training. This finding contrasts with other findings reporting cognitive improvements in men after six months of resistance exercise, suggesting a potential influence of sex on the impact of resistance exercise.
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Thirdly, based on the available results that resistance exercise may selectively preserve or enhance cognitive function by reversing specific pathologies or enhancing resilience in Alzheimer’s disease-associated areas. Baseline cognitive function may also modify the effects, as several trials have consistently shown that the structural changes associated with resistance exercise, such as slower atrophy and reversed white matter lesions in Alzheimer’s disease-associated brain structures, appear more prevalent in participants with established cognitive impairments(11).
Summary
Overall, it appears that there is significant potential for resistance exercise to delay the development of Alzheimer’s disease dementia or even reverse mild cognitive impairment conditions, at least if implemented early in the disease continuum and practiced consistently.
However, there are many open questions around resistance exercise interventions for Alzheimer’s disease prevention and treatment, including the optimal dose, intensity, time for implementation to maximize the clinical benefits, and the relationship between structural changes and functional improvements.
Hence, more robust studies are needed to comprehensively address these uncertainties. However, based on the evidence to date, it is cautiously suggested that resistance exercise may reverse relevant pathological structural changes and improve associated cognitive functions if performed at least twice per week for at least six months, with greatest effects in those already experiencing some element of cognitive decline.
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References:
1. Association AP: Diagnostic and statistical manual of mental disorders, (ed 5th), American Psychiatric Association, 2022
2. Livingston G, Huntley J, Sommerlad A, et al: Dementia prevention, intervention, and care: 2020 report of the Lancet Commission. The Lancet 396:413-446, 2020
3. Diamond A, Ling DS: Review of the evidence on, and fundamental questions about, efforts to improve executive functions, including working memory. Cognitive and working memory training: Perspectives from psychology, neuroscience, and human development:143-431, 2020
4. McArdle WD, Katch FI, Katch VL: Exercise physiology: nutrition, energy, and human performance, Lippincott Williams & Wilkins, 2010
5. Jonasson LS, Nyberg L, Kramer AF, et al: Aerobic exercise intervention, cognitive performance, and brain structure: results from the physical influences on brain in aging (PHIBRA) study. Frontiers in aging neuroscience 8:336, 2017
6. Turrini S, Wong B, Eldaief M, et al: The multifactorial nature of healthy brain ageing: Brain changes, functional decline and protective factors. Ageing Research Reviews 88:101939, 2023
7. Leong RL, Lo JC, Sim SK, et al: Longitudinal brain structure and cognitive changes over 8 years in an East Asian cohort. Neuroimage 147:852-860, 2017
8. Harada CN, Love MCN, Triebel KL: Normal cognitive aging. Clinics in geriatric medicine 29:737-752, 2013
9. Best JR, Chiu BK, Hsu CL, et al: Long-term effects of resistance exercise training on cognition and brain volume in older women: results from a randomized controlled trial. Journal of the international neuropsychological society 21:745-756, 2015
10. Bolandzadeh N, Tam R, Handy TC, et al: Resistance training and white matter lesion progression in older women: exploratory analysis of a 12‐month randomized controlled trial. Journal of the American Geriatrics Society 63:2052-2060, 2015
11. Broadhouse KM, Singh MF, Suo C, et al: Hippocampal plasticity underpins long-term cognitive gains from resistance exercise in MCI. NeuroImage: Clinical 25:102182, 2020
12. Suo C, Singh MF, Gates N, et al: Therapeutically relevant structural and functional mechanisms triggered by physical and cognitive exercise. Molecular psychiatry 21:1633-1642, 2016
