pCO2 Oscillations During Exercise: Relation to Cerebral Blood Flow and to Cognitive Dysfunction in COPD
Condition: Chronic Obstructive Pulmonary Disease
MeSH terms: Lung Diseases, Obstructive; Pulmonary Disease, Chronic Obstructive; Cognitive Dysfunction
Study type: Interventional

Summary: 
      Investigators wish to identify a relationship between substantial changes in carbon dioxide
      partial-pressure (pCO2), which frequently occur during the transitions from rest to exercise
      (ΔpCO2 >4 millimeters of mercury [mmHg] from baseline), and the prevalence of cognitive
      dysfunction in COPD. In particular, it is anticipated to investigate the vascular effect of
      pCO2 oscillations in the regulation of cerebral blood flow (CBF) during exercise and its
      impact on cognitive function in Chronic Obstructive Pulmonary Disease (COPD). Furthermore,
      this study aims to examine whether major pCO2 oscillations have prognostic value in cognitive
      deterioration at 6, 12, and 18-month follow-up. In addition, the acute effect of 3-week
      pulmonary rehabilitation (PR) on cognitive function will be explored. The evaluation of
      cognitive function will be performed by the use of Standardized Mini Mental State Examination
      (SMMSE), Addenbrooke's Cognitive Examination (ACE-R), Montreal Cognitive Assessment (MoCA),
      and Telephone Interview for Cognitive Status (TICS) assessing several cognitive domains
      (cognitive scores) whereas Stroop test [color reading interference] will be used for
      measuring cognitive performance (Reaction-Time).
    

Detailed description: 
      Cerebral Blood Flow (CBF) regulation is crucial for the adequate oxygen supply to the brain
      and the sustenance of cerebrovascular reserve capacity. A fundamental physiologic regulator
      of CBF is the carbon dioxide partial pressure (pCO2), which determines the dilatation or
      contraction of cerebral vasculature. CBF regulation response has been found to be strongly
      dependent upon pCO2 but much less so upon changes in arterial oxygen saturation. CBF is
      highly sensitive to pCO2 changes which cause pronounced-vasodilatation in increased pCO2 (CBF
      augmentation) or vasoconstriction in decreased pCO2 levels (CBF diminution). During cerebral
      activation and increased metabolism, cerebral arterioles dilate contributing to increase CBF
      but this process is often challenged during exercise and has a potential impact on cognitive
      function. CBF is linked to cognitive function while serum level of Brain Derived Neurotrophic
      Factor (BDNF) has been shown as a critical driving force behind neural plasticity with a
      potential utility as a biomarker of cognitive decline.

      Investigators assume that major pCO2 oscillations during exercise (ΔpCO2 >4 millimeters of
      mercury [mmHg] from baseline) as a reflection of the abnormality in ventilatory
      efficiency/drive, lead to overall and local disturbances of cerebral blood flow (CBF) and
      thus can be associated to increased prevalence of cognitive dysfunction in patients with
      Chronic Obstructive Pulmonary Disease (COPD). Moreover, investigators hypothesize that
      patients with major pCO2 oscillations during exercise may develop worse cognitive impairment
      in several cognitive domains and greater cognitive decline compared to "isocapnic" patients
      at 6, 12, and 18-month follow-up. Inpatient PR may benefit cognitive function by improving
      breathing (diminishing pCO2 oscillations), therefore improving CBF, and by increasing
      cerebral neural activation through exercise.

      With regard to cognitive dysfunction, which is associated to increased all-cause mortality
      and disability, investigators wish:

      (A) to detect a relationship between major pCO2 oscillations during exercise and increased
      prevalence of cognitive dysfunction in COPD; (B) to investigate the impact of different pCO2
      transitory-patterns (1. pCO2: decline/ hypocapnic, 2. steady/ isocapnic, 3. increase/
      hypercapnic) on CBF regulation and cognitive function; (C) to examine whether major pCO2
      oscillations can be a determinant of greater cognitive deterioration in several cognitive
      domains at 6, 12, and18-month follow-up and (D) to explore the acute effect of 3-week PR on
      pCO2 oscillations and CBF in respect to cognitive function in COPD patients with cognitive
      impairment.

      The evaluation of cognitive function will be performed by the use of Standardized Mini Mental
      State Examination (SMMSE), Addenbrooke's Cognitive Examination (ACE-R), Montreal Cognitive
      Assessment (MoCA) and Telephone Interview for Cognitive Status (TICS) assessing several
      cognitive domains (cognitive scores) whereas Stroop test will be used for measuring cognitive
      performance (Reaction-Time).
    

Intervention name(s): Pulmonary Rehabilitation program
Intervention type(s): Other
Intervention description(s): Patients will attend a comprehensive 3-week PR program (12sessions/ 60min·day) including high intensive interval exercise equivalent to 100% of peak work rate (WRpeak) with 30sec work periods interspersed with 30sec rest periods for 30min and light resistance training (3muscle groups/ 4sets each/10repetitions; ~30min).
Other intervention name(s): Exercise intervention
Allocation: Non-Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Primary purpose: Basic Science
Keywords: COPD; Carbon dioxide partial pressure (pCO2); Cerebral blood flow (CBF); Cognitive dysfunction; Mild/Moderate Cognitive Impairment (MCI); Pulmonary Rehabilitation (PR); Standardized Mini Mental State Examination (SMMSE); Addenbrooke's Cognitive Examination (ACE-R); Montreal Cognitive Assessment (MoCA); Telephone Interview for Cognitive Status (TICS); Stroop test (Reaction Time)