Moderate‐ to high‐intensity exercise does not modify cortical β‐amyloid in Alzheimer's disease

Frederiksen, Kristian Steen; Madsen, Karine; Andersen, Birgitte; Beyer, Nina; Garde, Ellen; Høgh, Peter; Waldemar, Gunhild; Hasselbalch, Steen G.; Law, Ian

doi:10.1016/j.trci.2019.04.006

Cited by 24 publications

(28 citation statements)

References 87 publications

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“…However, small human intervention studies have examined the impact of exercise on amyloid with inconclusive results. At least three intervention studies have examined the impact of exercise on serum amyloid concentration, with none reporting reliable reductions in amyloid as a consequence of exercise [ 62 – 64 ]. The amyloid tracer we employed (18F-AV45) may lack sufficient sensitivity/specificity to index subtle changes in amyloid induced by exercise in cognitively normal older adults.…”

Section: Discussionmentioning

confidence: 99%

Effect of aerobic exercise on amyloid accumulation in preclinical Alzheimer’s: A 1-year randomized controlled trial

et al. 2021

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Background Our goal was to investigate the role of physical exercise to protect brain health as we age, including the potential to mitigate Alzheimer’s-related pathology. We assessed the effect of 52 weeks of a supervised aerobic exercise program on amyloid accumulation, cognitive performance, and brain volume in cognitively normal older adults with elevated and sub-threshold levels of cerebral amyloid as measured by amyloid PET imaging. Methods and findings This 52-week randomized controlled trial compared the effects of 150 minutes per week of aerobic exercise vs. education control intervention. A total of 117 underactive older adults (mean age 72.9 [7.7]) without evidence of cognitive impairment, with elevated (n = 79) or subthreshold (n = 38) levels of cerebral amyloid were randomized, and 110 participants completed the study. Exercise was conducted with supervision and monitoring by trained exercise specialists. We conducted 18F-AV45 PET imaging of cerebral amyloid and anatomical MRI for whole brain and hippocampal volume at baseline and Week 52 follow-up to index brain health. Neuropsychological tests were conducted at baseline, Week 26, and Week 52 to assess executive function, verbal memory, and visuospatial cognitive domains. Cardiorespiratory fitness testing was performed at baseline and Week 52 to assess response to exercise. The aerobic exercise group significantly improved cardiorespiratory fitness (11% vs. 1% in the control group) but there were no differences in change measures of amyloid, brain volume, or cognitive performance compared to control. Conclusions Aerobic exercise was not associated with reduced amyloid accumulation in cognitively normal older adults with cerebral amyloid. In spite of strong systemic cardiorespiratory effects of the intervention, the observed lack of cognitive or brain structure benefits suggests brain benefits of exercise reported in other studies are likely to be related to non-amyloid effects. Trial registration NCT02000583; ClinicalTrials.gov.

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Section: Discussionmentioning

confidence: 99%

Effect of aerobic exercise on amyloid accumulation in preclinical Alzheimer’s: A 1-year randomized controlled trial

et al. 2021

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“…In contrast, the microscopical signs of Aβ deposits were not detectable after physical activity. Although cortical accumulation of Aβ has not been altered in high-intensity training (Frederiksen et al, 2019), it has also been published that training and running have a protective effect in the hippocampus of mice in AD (Schimidt et al, 2019). Although physical activity generally decreases the amount of Aβ deposits or concentration in the blood and cerebrospinal fluid (Brown et al, 2019), no data are available to clarify the mechanism in the periphery.…”

Section: Discussionmentioning

confidence: 99%

Physical Activity Protects the Pathological Alterations of Alzheimer’s Disease Kidneys via the Activation of PACAP and BMP Signaling Pathways

Perényi

Szegeczki

Horváth

et al. 2020

Front. Cell. Neurosci.

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Alzheimer's disease (AD) is a neurodegenerative disorder with typical amyloid beta (Aβ) aggregations. Elimination of the Aβ precursors via the kidneys makes the organ a potential factor in the systemic degeneration leading to AD. Pituitary adenylate cyclase-activating polypeptide (PACAP) exerts neuroprotective effects in AD and plays a protective role in kidney pathologies. Increased physical activity is preventive of the formation of AD, but its detailed mechanism and possible connections with PACAP have not been clarified. In the kidneys of AD mice, the effects of physical activity were investigated by comparing wild-type and AD organs. Aβ plaque formation was reduced in AD kidneys after increased training (TAD). Mechanotransduction elevated PACAP receptor expression in TAD mice and normalized the protein kinase A (PKA)-mediated pathways. BMP4/BMPR1 elevation activated Smad1 expression and normalized collagen type IV in TAD animals. In conclusion, our data suggest that elevated physical activity can prevent the AD-induced pathological changes in the kidneys via, at least in part, the activation of PACAP-BMP signaling crosstalk.

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“…Other studies have found no effect on cortical A

levels (evaluated using PET) when patients with mild to moderate AD (assessed according to the NINCDS-ADRDA Alzheimers Criteria and DSM-IV codes [ 93 ]) undertook a 16 week exercise intervention (moderate to high intensity aerobic exercise three times weekly for one hour). In this case, the lack of efficacy may be due to the short intervention period, and relatively late stage of AD progression [ 94 ]. While changes in AD pathology have been demonstrated in a number of studies, these do not always translate to improvements in cognitive function.…”

Section: Exercise and Ad Protectionmentioning

confidence: 99%

The Protective Effect of Exercise in Neurodegenerative Diseases: The Potential Role of Extracellular Vesicles

Fuller

Whitham

Mathivanan

et al. 2020

Cells

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Physical activity has systemic effects on the body, affecting almost every organ. It is important not only for general health and wellbeing, but also in the prevention of diseases. The mechanisms behind the therapeutic effects of physical activity are not completely understood; however, studies indicate these benefits are not confined to simply managing energy balance and body weight. They also include systemic factors which are released into the circulation during exercise and which appear to underlie the myriad of benefits exercise can elicit. It was shown that along with a number of classical cytokines, active tissues also engage in inter-tissue communication via extracellular vesicles (EVs), specifically exosomes and other small EVs, which are able to deliver biomolecules to cells and alter their metabolism. Thus, EVs may play a role in the acute and systemic adaptations that take place during and after physical activity, and may be therapeutically useful in the treatment of a range of diseases, including metabolic disorders such as type 2 diabetes and obesity; and the focus of this review, neurological disorders such as Alzheimer’s disease.

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Moderate‐ to high‐intensity exercise does not modify cortical β‐amyloid in Alzheimer's disease

Cited by 24 publications

References 87 publications

Effect of aerobic exercise on amyloid accumulation in preclinical Alzheimer’s: A 1-year randomized controlled trial

Effect of aerobic exercise on amyloid accumulation in preclinical Alzheimer’s: A 1-year randomized controlled trial

Physical Activity Protects the Pathological Alterations of Alzheimer’s Disease Kidneys via the Activation of PACAP and BMP Signaling Pathways

The Protective Effect of Exercise in Neurodegenerative Diseases: The Potential Role of Extracellular Vesicles

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