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Cognitive Impairment in Idiopathic Pulmonary Fibrosis


Pulmonary fibrosis describes the group of fibrosing interstitial lung diseases (ILDs) that cause progressive scarring of the alveolar interstitium and often lead to hypoxemic respiratory failure. ILDs encompass a large and diverse group of parenchymal lung disorders, including those associated with diseases of unknown cause (idiopathic interstitial pneumonias) and other diseases (connective tissue disease associated ILDs, chronic sarcoidosis) or environmental exposures (chronic hypersensitivity pneumonia). .
Idiopathic pulmonary fibrosis (IPF), the most extensively studied type of ILD, is a steadily progressive lung disease with a prognosis that can be worse than many cancers. With a median survival time of 2.5-3.5 years after diagnosis, IPF shows significant morbidity and mortality outcomes, not all of which are directly related to progressive fibrotic disease itself.
Cognitive Impairment in Idiopathic Pulmonary FibrosisThis elderly population, with an average age of 66 at diagnosis, often experiences a variety of comorbidities that affect the clinical spectrum of the disease, progression, and mortality. Analysis of 272 IPF patients reported that 58% of cases had one, two or three comorbid conditions, 30% had four to seven comorbid conditions, and only 12% had no comorbidity. Respiratory comorbidities, including emphysema (8-34%), obstructive sleep apnea (58-88%), lung cancer (3-22%) and pulmonary hypertension (3-84%), although estimates differ widely, many studies have depending on the source population. It is developing.
Non-respiratory diseases such as gastroesophageal reflux (30-80%), systemic arterial hypertension (14-71%), ischemic heart disease (4-68%), diabetes mellitus type 2 (10-33%) and depression (10-33%). comorbidities 12-49%) are also a very common condition.

Risk Factors for Cognitive Deficits in Patients with IPF

Regarding IPF or associated morbidity, there are several potential factors and conditions for the occurrence of a cognitive deficit. Hypoxemia, smoking history, aging, and the chronic evolution of the disease are potential factors for the emergence of a cognitive deficit. Difficulties in breathing (increased internal elastic load of respiratory muscles and stimulation of peripheral mechanoreceptors), nocturnal cough, medications, hypoxemia, and obstructive apnea can alter the quality of life.

Physiopathology of Cognitive Impairment in Patients with IPF

IPF patients develop progressive respiratory restriction and exercise intolerance. Changing blood gases is a common feature in IPF pathophysiology. Patients experience transient or persistent hypoxia over a significant cumulative time with DPT at less than 2.90%. Nocturnal hypoxia is common in chronic fibrotic interstitial lung diseases, both in patients who associate OSA such as those without this comorbidity. In the absence of OSA, nocturnal hypoxia may be the result of alveolar hypoventilation, altered ventilation-perfusion rate and desaturation tendency due to patients on the immediate part of the oxygen-hemoglobin dissociation curve.
Epidemiological research has shown that besides genetic and environmental factors such as lifestyles and cardiovascular risk factors, decreased lung function is also associated with dementia and cognitive impairment in the general population. In a large population-based cohort participating in the Atherosclerosis Risk Study in Communities, the presence of a restrictive ventilation pattern was associated with poorer performance on cognitive assessments and an increased risk of dementia hospitalization.
A recent prospective study found that patients with restrictive lung disease had almost twice the chance of developing dementia or mild cognitive impairment than healthy individuals. Researchers have followed over 14,000 middle-aged people for over 23 years. Lung disease and impaired lung function were associated with a higher risk of dementia and mild cognitive impairment through both Alzheimer’s disease and cerebrovascular etiologies.
Although both COPD and restrictive disorder are associated with an increased risk of dementia phenotypes, the magnitudes of the association are most pronounced for restrictive impairment. There is no difference between smokers and non-smokers. Different pathogenic mechanisms may explain the relationship of lung function with cognitive performance and risk of dementia. Chronic hypoxia can lead to ischemic brain damage and neurodegeneration because prospective studies have found that individuals with reduced lung function or decreased arterial oxygen saturation are more likely to develop white matter lesions and lacunar infarction.
A restrictive ventilation pattern has been associated with an increased incidence of diabetes and subclinical atherosclerosis and an increased risk of cardiovascular outcomes. In turn, diabetes and cardiovascular disease can cause cognitive impairment and increase the risk of dementia. Worse lung function can lead to cognitive impairment and dementia through the development of a proinflammatory state. Higher C-reactive protein levels in people with reduced lung function have been associated with a higher risk of dementia.
It is surprising that very few studies have investigated cognitive impairment in IPF, a disease with the potential to develop rapid and frequent hypoxemia. In a limited study, with only seven IPF patients undergoing pulmonary rehabilitation, applying five sets of psychometric tests (verbal recall of information, continuous visual attention, efficiency in completing sequential tasks, verbal fluency, visual-spatial and graphomotor competence) were found to be impaired. This cognition is only at the level of visual attention.
A prospective, observational study examining cognitive function in 30 IPF patients with normal oxygen saturation and comparing them with COPD and smoking controls shows that almost half of IPF patients have mild cognitive dysfunction and cannot be explained by age. In a prospective, cross-sectional, descriptive study, Bors et al. showed that individuals with severe IPF had worse cognitive function than those with mild to moderate disease and controls.Cognitive Impairment in Idiopathic Pulmonary Fibrosis
Participants were assessed with five neuropsychological tests that assess various domains of cognitive function: attention rate, sequencing, mental flexibility, visual search and motor function, information processing speed, selective attention, cognitive flexibility, executive function, verbal recall and recognition assessment, and accessibility of lexical and semantic information. specific related cognitive deficits. Severe IPF patients had significantly lower performance on tasks requiring speed-split attention and had slower processing speeds when a familiar response required suppression.
A cross-sectional study aimed at assessing cognition and identifying clinical cognitive modifiers in IPF and 23 IPF patients were evaluated using the Montreal Cognitive Assessment (MoCA). As mentioned earlier, MoCA is a screening tool with high specificity and sensitivity for detecting early cognitive impairments and has been validated in multiple settings and disorders. MoCA evaluates various cognitive domains (short-term memory, visual-spatial abilities, executive functions, attention, concentration and working memory, language, time and place orientation) to differentiate healthy cognitive aging from mild cognitive impairment. The study found a mild cognitive impairment in patients with IPF related to visual-spatial abilities, language, and working memory areas. Obstructive sleep apnea was quite common in these patients (more than 80% of cases) and there is a significant correlation between cognitive function and the severity of the apnea-hypopnea index. Poor sleep quality is often met through sleep-disordered breathing, including OSA, in IPF, indicating increased sleep disruption, decreased slow-wave and REM sleep, and sleep oxygen desaturation.

Managing Cognitive Deficit in IPF PatientsCognitive Impairment in Idiopathic Pulmonary Fibrosis

It is particularly important in this patient population, given the health-related quality of life, lack of treatment options, low mortality, and rapid progression of the disease. IPF-associated morbidity has a wide and profound impact on the patient’s quality of life. Therefore, cognition level and other patient-centered results are important goals that should be evaluated in clinical research and practice. We currently do not have a specific cognitive assessment tool for IPF, so researchers used validated tools in cognitive analysis of other chronic respiratory diseases. The potential problem is that these tools fail to capture many of the effects of IPF on patients’ lives.

References:
https://erj.ersjournals.com/content/54/suppl_63/PA1305
https://pubmed.ncbi.nlm.nih.gov/26374298/

Author: Ozlem Guvenc Agaoglu


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