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Association between physical activity and dementia’s risk factors in patients with Parkinson’s disease

  • Mohammad Alwardat
  • Tommaso SchirinziEmail author
  • Giulia Di Lazzaro
  • Giulia Maria Sancesario
  • Donatella Franco
  • Paola Imbriani
  • Paola Sinibaldi Salimei
  • Sergio Bernardini
  • Nicola Biagio Mercuri
  • Antonio Pisani
Neurology and Preclinical Neurological Studies - Original Article

Abstract

Evidence suggests that physical activity (PA) exerts beneficial effects on neurodegenerative processes, either as symptomatic relief or disease-modifying strategy. Actually, it may represent a viable neuroprotective intervention in Parkinson’s disease dementia (PDD), a severe, frequent, and untreatable complication of Parkinson’s disease (PD). According to such hypothesis, this cross-sectional study tested, in PD patients, the association between levels of PA and well-known risk factors for PDD, such as mood disorders and amyloid-β42 CSF content. Amount of PA was measured by the International Physical Activity Questionnaires—Short Form (IPAQ–SF) in 128 cognitively intact PD patients and correlated with the Hamilton-Depression (HAM-D) and the Hamilton-Anxiety (HAM-A) scores; in a homogenous subgroup of 40 patients, it was further correlated with a panel of CSF biomarkers, including amyloid-β42, total α-synuclein, total, and phosphorylated tau. The statistical model was corrected for the main potential confounding factors (motor impairment, dopaminergic treatment, disease duration, age, and sex). Both the HAM-A and HAM-D scores, as well as the Aβ42 CSF content, improved in parallel with the increase of the total week amount of PA. Although with several limitations, we preliminarily demonstrated that a high level of PA is associated with a more favourable profile of PDD risk factors, in terms of both mood disturbances and CSF markers of neurodegeneration. However, confirmative studies are necessary to validate the efficacy of PA as protective intervention for PDD.

Keywords

Parkinson’s disease Physical activity Parkinson’s disease dementia Frailty CSF biomarkers Neuroprotection 

Notes

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.

Ethical approval

The “Tor Vergata University Hospital” Ethics Committee approved the study; the study also respected the ethical standards of Helsinki declaration. Participants provided informed consent.

References

  1. Artusi CA, Mishra M, Latimer P et al (2018) Integration of technology-based outcome measures in clinical trials of Parkinson and other neurodegenerative diseases. Parkinson Relat Disord 46:S53–S56.  https://doi.org/10.1016/j.parkreldis.2017.07.022 CrossRefGoogle Scholar
  2. Blennow K, Hampel H, Weiner M, Zetterberg H (2010) Cerebrospinal fluid and plasma biomarkers in Alzheimer disease. Nat Publ Gr 6:131–144.  https://doi.org/10.1038/nrneurol.2010.4 Google Scholar
  3. Blennow K, Biscetti L, Eusebi P, Parnetti L (2016) Cerebrospinal fluid biomarkers in Alzheimer’s and Parkinson’s diseases-from pathophysiology to clinical practice. Mov Disord 31:836–847.  https://doi.org/10.1002/mds.26656 CrossRefGoogle Scholar
  4. Compta Y, Parkkinen L, O’Sullivan SS et al (2011) Lewy- and Alzheimer-type pathologies in Parkinson’s disease dementia: which is more important? Brain 134:1493–1505.  https://doi.org/10.1093/brain/awr031 CrossRefGoogle Scholar
  5. Cusso ME, Donald KJ, Khoo TK (2016) The impact of physical activity on non-motor symptoms in Parkinson’s disease: a systematic review. Front Med 3:35.  https://doi.org/10.3389/fmed.2016.00035 CrossRefGoogle Scholar
  6. Dissanayaka NNW, Lawson RA, Yarnall AJ et al (2017) Anxiety is associated with cognitive impairment in newly-diagnosed Parkinson’s disease. Parkinson Relat Disord 36:63–68.  https://doi.org/10.1016/j.parkreldis.2017.01.001 CrossRefGoogle Scholar
  7. Dorr A, Sahota B, Chinta LV et al (2012) Amyloid-β-dependent compromise of microvascular structure and function in a model of Alzheimer’s disease. Brain 135:3039–3050.  https://doi.org/10.1093/brain/aws243 CrossRefGoogle Scholar
  8. Fava GA, Kellner R, Munari F, Pavan L (1982) The Hamilton depression rating scale in normals and depressives. Acta Psychiatr Scand 66:26–32CrossRefGoogle Scholar
  9. Gratwicke J, Jahanshahi M, Foltynie T (2015) Parkinson’s disease dementia: a neural networks perspective. Brain 138:1454–1476.  https://doi.org/10.1093/brain/awv104 CrossRefGoogle Scholar
  10. Halliday GM, Leverenz JB, Schneider JS, Adler CH (2014) The neurobiological basis of cognitive impairment in Parkinson’s disease. Mov Disord 29:634–650.  https://doi.org/10.1002/mds.25857 CrossRefGoogle Scholar
  11. Hamilton M (1959) The assessment of anxiety states by rating. Br J Med Psychol 32:50–55CrossRefGoogle Scholar
  12. Huang T, Larsen KT, Ried-Larsen M et al (2014) The effects of physical activity and exercise on brain-derived neurotrophic factor in healthy humans: a review. Scand J Med Sci Sports 24:1–10.  https://doi.org/10.1111/sms.12069 CrossRefGoogle Scholar
  13. Hughes AJ, Daniel SE, Kilford L, Lees AJ (1992) Accuracy of clinical diagnosis of idiopathic Parkinson’s disease: a clinico-pathological study of 100 cases. J Neurol Neurosurg Psychiatry 55:181–184CrossRefGoogle Scholar
  14. Jessen NA, Munk ASF, Lundgaard I, Nedergaard M (2015) The glymphatic system: a beginner’s guide. Neurochem Res 40:2583–2599.  https://doi.org/10.1007/s11064-015-1581-6 CrossRefGoogle Scholar
  15. Johar I, Mollenhauer B, Aarsland D (2017) Cerebrospinal fluid biomarkers of cognitive decline in Parkinson’s disease. Int Rev Neurobiol 132:275–294.  https://doi.org/10.1016/bs.irn.2016.12.001 CrossRefGoogle Scholar
  16. Joling M, van den Heuvel OA, Berendse HW et al (2018) Serotonin transporter binding and anxiety symptoms in Parkinson’s disease. J Neurol Neurosurg Psychiatry 89:89–94.  https://doi.org/10.1136/jnnp-2017-316193 CrossRefGoogle Scholar
  17. Kalia LV, Lang AE (2015) Parkinson’s disease. Lancet 386:896–912.  https://doi.org/10.1016/S0140-6736(14)61393-3 CrossRefGoogle Scholar
  18. Kotagal V, Spino C, Bohnen NI et al (2018) Serotonin, β-amyloid, and cognition in Parkinson disease. Ann Neurol.  https://doi.org/10.1002/ana.25236 Google Scholar
  19. Kulisevsky J, Oliveira L, Fox SH (2018) Update in therapeutic strategies for Parkinsonʼs disease. Curr Opin Neurol.  https://doi.org/10.1097/WCO.0000000000000579 Google Scholar
  20. Law LL, Rol RN, Schultz SA et al (2018) Moderate intensity physical activity associates with CSF biomarkers in a cohort at risk for Alzheimer’s disease. Alzheimer Dement (Amsterdam Netherlands) 10:188–195.  https://doi.org/10.1016/j.dadm.2018.01.001 Google Scholar
  21. Liu PZ, Nusslock R (2018) Exercise-mediated neurogenesis in the Hippocampus via BDNF. Front Neurosci 12:52.  https://doi.org/10.3389/fnins.2018.00052 CrossRefGoogle Scholar
  22. Mak MK, Wong-Yu IS, Shen X, Chung CL (2017) Long-term effects of exercise and physical therapy in people with Parkinson disease. Nat Rev Neurol 13:689–703.  https://doi.org/10.1038/nrneurol.2017.128 CrossRefGoogle Scholar
  23. Maltese M, Stanic J, Tassone A et al (2018) Early structural and functional plasticity alterations in a susceptibility period of DYT1 dystonia mouse striatum. Elife.  https://doi.org/10.7554/eLife.33331 Google Scholar
  24. Mannocci A, Thiene D, Di Cimmuto A, Del et al (2010) International Physical Activity Questionnaire: validation and assessment in an Italian sample. Ital J Public Health.  https://doi.org/10.2427/5694 Google Scholar
  25. Marinus J, Zhu K, Marras C et al (2018) Risk factors for non-motor symptoms in Parkinson’s disease. Lancet Neurol 17:559–568.  https://doi.org/10.1016/S1474-4422(18)30127-3 CrossRefGoogle Scholar
  26. Martorana A, Di Lorenzo F, Belli L et al (2015) Cerebrospinal fluid Aβ42 levels: when physiological become pathological state. CNS Neurosci Ther 21:921–925.  https://doi.org/10.1111/cns.12476 CrossRefGoogle Scholar
  27. Measso G, Cavarzeran F, Zappalà G et al (1993) The mini-mental state examination: normative study of an Italian random sample. Dev Neuropsychol 9:77–85.  https://doi.org/10.1080/87565649109540545 CrossRefGoogle Scholar
  28. Moore KM, Girens RE, Larson SK et al (2016) A spectrum of exercise training reduces soluble Aβ in a dose-dependent manner in a mouse model of Alzheimer’s disease. Neurobiol Dis 85:218–224.  https://doi.org/10.1016/j.nbd.2015.11.004 CrossRefGoogle Scholar
  29. Ngandu T, Lehtisalo J, Solomon A et al (2015) A 2 year multidomain intervention of diet, exercise, cognitive training, and vascular risk monitoring versus control to prevent cognitive decline in at-risk elderly people (FINGER): a randomised controlled trial. Lancet 385:2255–2263.  https://doi.org/10.1016/S0140-6736(15)60461-5 CrossRefGoogle Scholar
  30. Pietrelli A, Matkovic L, Vacotto M et al (2018) Aerobic exercise upregulates the BDNF-Serotonin systems and improves the cognitive function in rats. Neurobiol Learn Mem.  https://doi.org/10.1016/j.nlm.2018.05.007 Google Scholar
  31. Politis M, Niccolini F (2015) Serotonin in Parkinson’s disease. Behav Brain Res 277:136–145.  https://doi.org/10.1016/j.bbr.2014.07.037 CrossRefGoogle Scholar
  32. Ryan SM, Kelly ÁM (2016) Exercise as a pro-cognitive, pro-neurogenic and anti-inflammatory intervention in transgenic mouse models of Alzheimer’s disease. Ageing Res Rev 27:77–92.  https://doi.org/10.1016/j.arr.2016.03.007 CrossRefGoogle Scholar
  33. Sancesario GM, Bernardini S (2015) How many biomarkers to discriminate neurodegenerative dementia? Crit Rev Clin Lab Sci 52:314–326.  https://doi.org/10.3109/10408363.2015.1051658 CrossRefGoogle Scholar
  34. Schirinzi T, Sancesario GM, Ialongo C et al (2015) A clinical and biochemical analysis in the differential diagnosis of idiopathic normal pressure hydrocephalus. Front Neurol 6:86.  https://doi.org/10.3389/fneur.2015.00086 CrossRefGoogle Scholar
  35. Schirinzi T, Madeo G, Martella G et al (2016) Early synaptic dysfunction in Parkinson’s disease: Insights from animal models. Mov Disord 31:802–813.  https://doi.org/10.1002/mds.26620 CrossRefGoogle Scholar
  36. Schirinzi T, Di Lazzaro G, Sancesario GM et al (2017) Levels of amyloid-beta-42 and CSF pressure are directly related in patients with Alzheimer’s disease. J Neural Transm.  https://doi.org/10.1007/s00702-017-1786-8 Google Scholar
  37. Schirinzi T, Di Lorenzo F, Sancesario GM et al (2018a) Amyloid-mediated cholinergic dysfunction in motor impairment related to Alzheimer’s disease. J Alzheimer’s Dis 64:525–532.  https://doi.org/10.3233/JAD-171166 CrossRefGoogle Scholar
  38. Schirinzi T, Sancesario GM, Di Lazzaro G et al (2018b) CSF α-synuclein inversely correlates with non-motor symptoms in a cohort of PD patients. Parkinson Relat Disord.  https://doi.org/10.1016/j.parkreldis.2018.10.018 Google Scholar
  39. Schirinzi T, Sancesario GM, Di Lazzaro G et al (2018c) Clinical value of CSF amyloid-beta-42 and tau proteins in progressive supranuclear palsy. J Neural Transm.  https://doi.org/10.1007/s00702-018-1893-1 Google Scholar
  40. Schirinzi T, Sancesario GM, Di Lazzaro G et al (2018d) Cerebrospinal fluid biomarkers profile of idiopathic normal pressure hydrocephalus. J Neural Transm.  https://doi.org/10.1007/s00702-018-1842-z Google Scholar
  41. Sleiman SF, Chao MV (2015) Downstream consequences of exercise through the action of BDNF. Brain Plast 1:143–148.  https://doi.org/10.3233/BPL-150017 CrossRefGoogle Scholar
  42. Tarumi T, Zhang R (2018) Cerebral blood flow in normal aging adults: cardiovascular determinants, clinical implications, and aerobic fitness. J Neurochem 144:595–608.  https://doi.org/10.1111/jnc.14234 CrossRefGoogle Scholar
  43. Wang H-F, Yu J-T, Tang S-W et al (2015) Efficacy and safety of cholinesterase inhibitors and memantine in cognitive impairment in Parkinson’s disease, Parkinson’s disease dementia, and dementia with Lewy bodies: systematic review with meta-analysis and trial sequential analysis. J Neurol Neurosurg Psychiatry 86:135–143.  https://doi.org/10.1136/jnnp-2014-307659 CrossRefGoogle Scholar

Copyright information

© Springer-Verlag GmbH Austria, part of Springer Nature 2019

Authors and Affiliations

  • Mohammad Alwardat
    • 1
  • Tommaso Schirinzi
    • 1
    Email author
  • Giulia Di Lazzaro
    • 1
  • Giulia Maria Sancesario
    • 2
  • Donatella Franco
    • 1
  • Paola Imbriani
    • 1
    • 4
  • Paola Sinibaldi Salimei
    • 3
  • Sergio Bernardini
    • 2
  • Nicola Biagio Mercuri
    • 1
    • 4
  • Antonio Pisani
    • 1
    • 4
  1. 1.Department of Systems MedicineUniversity of Roma “Tor Vergata”RomeItaly
  2. 2.Department of Experimental Medicine and SurgeryUniversity of Roma “Tor Vergata”RomeItaly
  3. 3.Department of Biomedicine and PreventionUniversity of Roma “Tor Vergata”RomeItaly
  4. 4.IRCCS Fondazione Santa LuciaRomeItaly

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