Effect of physical exercise on markers of neuronal dysfunction in cerebrospinal fluid in patients with Alzheimer's disease

Jensen, Christer; Portelius, Erik; Høgh, Peter; Wermuth, Lene; Blennow, Kaj; Zetterberg, Henrik; Hasselbalch, Steen G.; Simonsen, Anja Hviid

doi:10.1016/j.trci.2017.03.007

Cited by 27 publications

(26 citation statements)

References 36 publications

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“…The APOE genotypeinfluences several pathways related to AD, such as vascular damage, A-beta accumulation, cholesterol transport, and neuroinflammation [4]. In a small subsample of the ADEX patients, we could not detect an effect of exercise on CSF levels of biomarkers of AD pathology [43] or synaptic function [44], regardless of the patients' APOE genotype, and although this could be due to the small sample size, effects on other downstream pathways could be involved, such as positive effects on cerebral vasculature, improved cholesterol transport, or decreased neuroinflammation.…”

Section: Discussionmentioning

confidence: 80%

Patients with Alzheimer's disease who carry the APOE ε4 allele benefit more from physical exercise

Jensen

Simonsen

Siersma

et al. 2019

A&D Transl Res & Clin Interv

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Introduction Our group has completed an exercise study of 200 patients with mild Alzheimer's disease. We found improvements in cognitive, neuropsychiatric, and physical measures in the participants who adhered to the protocol. Epidemiological studies in healthy elderly suggest that exercise preserves cognitive and physical abilities to a higher extent in AP OE ε4 carriers. Methods In this post hoc subgroup analysis study, we investigated whether the beneficial effect of an exercise intervention in patients with mild AD was dependent on the patients' APOE genotype. Results We found that patients who were APOE ε4 carriers benefitted more from the exercise intervention by preservation of cognitive performance and improvement in physical measures. Discussion This exploratory study establishes a possible connection between the beneficial effects of exercise in AD and the patients' APOE genotype. These findings, if validated, could greatly impact the clinical management of patients with AD and those at risk for developing AD.

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Section: Discussionmentioning

confidence: 80%

Patients with Alzheimer's disease who carry the APOE ε4 allele benefit more from physical exercise

Jensen

Simonsen

Siersma

et al. 2019

A&D Transl Res & Clin Interv

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“…[ 69 , 70 ] But quite a number of trails were restricted by appropriate endpoints, which resulted in this individually cognitive interventions lack of the relevant endpoints whose efficacy we must adopt to analysis. Therefore, from our conclusion above, PE, MT, CCT all have beneficial effects on older adults with AD and MCI, especially PE [ 58 , 71 ] and MT [ 72 , 73 ] as relatively obtained easily interventions. AD and MCI are progressive neurodegenerative disorders, and are still incurable.…”

Section: Discussionmentioning

confidence: 84%

Comparison of multiple interventions for older adults with Alzheimer disease or mild cognitive impairment

Liang¹,

Xu²,

Lü

et al. 2018

Medicine

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Background:The increasing prevalence of Alzheimer disease (AD) emphasizes the need for effective treatments. Both pharmacological therapies such as nutrition therapy (NT) and nonpharmacologic therapies including traditional treatment or personalized treatment (e.g., physical exercise, music therapy, computerized cognitive training) have been approved for the treatment of AD or mild cognitive impairment (MCI) in numerous areas.Methods:The aim of this study was to compare 4 types of interventions, physical exercise (PE), music therapy (MT), computerized cognitive training (CCT), and NT, in older adults with mild to moderate AD or MCI and identify the most effective intervention for their cognitive function. We used a system of search strategies to identify relevant studies and include randomized controlled trials (RCTs), placebo-controlled trials evaluating the efficacy and safety of 4 interventions in patients with AD or MCI. We updated the relevant studies which were published before March 2017 as a full-text article. Using Bayesian network meta-analysis (NMA), we ranked cognitive ability based objectively on Mini-Mental State Examination (MMSE), and assessed neuropsychiatric symptoms based on Neuropsychiatric Inventory (NPI). Pairwise and network meta-analyses were sequentially performed for efficacy and safety of intervention compared to control group through RCTs included.Results:We included 17 RCTs. Fifteen trials (n = 1747) were pooled for cognition and no obvious heterogeneity was found (I2 = 21.7%, P = .212) in NMA, the mean difference (MD) of PE (MD = 2.1, confidence interval [CI]: 0.44–3.8) revealed that PE was significantly efficacious in the treatment group in terms of MMSE. Five trials (n = 660) assessed neuropsychiatric symptoms with an obvious heterogeneity (I2 = 61.6%, P = .034), the MD of CCT (MD = −7.7, CI: −14 to −2.4), revealing that CCT was significantly efficacious in NPI.Conclusions:As the first NMA comparing different interventions for AD and MCI, our study suggests that PE and CCT might have a significant improvement in cognition and neuropsychiatric symptoms respectively. Moreover, nonpharmacological therapies might be better than pharmacological therapies.

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“…29,30 However, in the handful of studies that have focused specifically on physical activity, there has not been a consistent relationship with level of physical activity and brain imaging levels of β-amyloid or CSF biomarkers of AD. [31][32][33] The paucity of human data makes it difficult to explicate the pathologic mechanisms underlying the association of a more active lifestyle with better cognition in older adults.…”

Section: Discussionmentioning

confidence: 99%

Physical activity, common brain pathologies, and cognition in community-dwelling older adults

Buchman

Wilson

et al. 2019

Neurology

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ObjectiveTo examine the associations of physical activity, Alzheimer disease (AD), and other brain pathologies and cognition in older adults.MethodsWe studied 454 brain autopsies from decedents in a clinical-pathologic cohort study. Nineteen cognitive tests were summarized in a global cognitive score. Total daily physical activity summarized continuous multiday recordings of activity during everyday living in the community setting. A global motor ability score summarized 10 supervised motor performance tests. A series of regression analyses were used to examine associations of physical activity, AD, and other brain pathologies with global cognition proximate to death controlling for age, sex, education, and motor abilities.ResultsHigher levels of total daily activity (estimate 0.148, 95% confidence interval 0.053–0.244, SE 0.049, p = 0.003) and better motor abilities (estimate 0.283, 95% confidence interval, 0.175–0.390, SE 0.055, p < 0.001) were independently associated with better cognition. These independent associations remained significant when terms for AD and other pathologies were added as well as in sensitivity analyses excluding cases with poor cognition or dementia. Adding interaction terms, the associations of total daily activity and motor abilities with cognition did not vary in individuals with and without dementia. The associations of AD and other pathologies with cognition did not vary with the levels of total daily activity or motor abilities.ConclusionsPhysical activity in older adults may provide cognitive reserve to maintain function independent of the accumulation of diverse brain pathologies. Further studies are needed to identify the molecular mechanisms underlying this potential reserve and to ensure the causal effects of physical activity.

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Effect of physical exercise on markers of neuronal dysfunction in cerebrospinal fluid in patients with Alzheimer's disease

Cited by 27 publications

References 36 publications

Patients with Alzheimer's disease who carry the APOE ε4 allele benefit more from physical exercise

Patients with Alzheimer's disease who carry the APOE ε4 allele benefit more from physical exercise

Comparison of multiple interventions for older adults with Alzheimer disease or mild cognitive impairment

Physical activity, common brain pathologies, and cognition in community-dwelling older adults

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