Prior researches suggest the presence of impaired lung function may be linked to cognitive impairment (CI). A recent study shows that lung disease, and specifically Chronic obstructive pulmonary disease (COPD) are associated to a greater risk of CI in a population of 14,184 individuals followed for over 23 years. Moreover, the study shows that low forced expiratory volume in 1 second (FEV1) is associated to an increased risk of dementia and MCI, indipendently of smoking habit.

Chronic obstructive pulmonary disease (COPD) is considered "a progressive but potentially treatable and preventable disease". The clinical view of COPD is moved from a lung-centered model to a novel one that considers COPD as an "umbrella" term encompassing different pulmonary and extra-pulmonary manifestations.

Prior researches suggest the presence of impaired lung function may be linked to cognitive impairment (CI). Among these studies, one prospective found that a diagnosis of COPD is associated with an increased risk of mild cognitive impairment (MCI), mainly nonamnestic MCI (NA-MCI), in a dose-response relationship between COPD duration and risk of MCI. Moreover, CI associated with severe COPD stage increases mortality. Among these studies only one shows that CI decreases adherence to pharmacological and non-pharmacological therapies. However, while it is well known that an MMSE score of 23-24 points or less is predictive of poor inhaler technique no studies report the impact of CI on PR outcomes. It has been reported that patients with MMSE < 24 walk lesser, at the basal level, than patients with a MMSE score > 24 (146 ±134 versus 242 ± 152 m) in the six minutes walking tests (6MWT) but no data are reported after rehabilitation. On the other hand, some papers report an association between participation in exercise rehabilitation programs and enhanced performance on cognitive tests.

The aim of this study is to compare cognitive functioning in patients with COPD referred for pulmonary rehabilitation to the response of the programme itself. More specific objectives of the present study are to:

• Study whether and to what extent CI in patients with COPD impacts outcomes of pulmonary rehabilitation such as 6MW distance (6MWD), Barthel and Borg scales for assessing dyspnea, Maugeri Foundation Respiratory Failure Questionnaire and the disease-specific respiratory quality of life (QoL) [St. George's Respiratory Questionnaire (SGRQ) and the Medical Research Council (MRC)].
• Investigate clinical and demographic characteristics of patients with COPD with cognitive impairment.

The hypothesize is that COPD patients with CI have worse response to PR compared with patients with no CI.

These results are important on the light of a personalized approach according to the so called "P4 medicine", for predictive, preventive, personalized and participatory Recently, the so-called "Rehabilomics" research framework, initially introduced r in traumatic brain injury rehabilitation, was applied on COPD rehabilitation. The "Rehabilomics" represents an exclusive and distinctive model in the path of the personalized-medicine approaches to rehabilitation. Thus, in previousstudy the Rehabilomics-like approach was used to afford the complexity of COPD rehabilitation, incorporating social/demographic data (i.e. gender, education, presence of a caregiver) clinical, psychological/emotional traits, genetics (i.e. DNA variants) and biological factors (i.e. DNA damage, levels of interleukins, et cet.) in a real life setting.

Inclusion Criteria:

• All patients admitted consecutively

Exclusion Criteria:

• None

Consecutive patients with moderate to very severe diagnosis of COPD, based on GOLD criteria [Global Initiative for Chronic Obstructive Lung Disease. Report 2020 https://goldcopd.org/wp-content/uploads/2019/11/GOLD-2020-REPORT-ver1.0wms.pdf\], who were admitted to inpatient clinic for a period of 3-4 weeks of comprehensive interdisciplinary pulmonary rehabilitation (PR) program from January 2012 to December 2019.