Airway Protective Mechanisms in PD (R01)

Aspiration pneumonia (APn) occurs at a disproportionately hig rate in patients with
Parkinson's disease (PD) versus healthy age-matched older adults. This is of particular
public health concern given that aspiration pneumonia infection is a leading cause of death
in persons with PD. The development of APn is multifactorial with aspiration of material from
disordered swallowing (dysphagia) without proper cough response being the main contributing
factor. These findings reflect the fact that both swallowing and cough are sensorimotor
behaviors, and thus require appropriate detection and scaling of a sensory stimulus in order
to produce an appropriate motor response.

The long-term goal of this research is to advance the management of airway protection
deficits in patients with neurodegenerative disease in order to decrease morbidity and
mortality due to aspiration related lung infection. The objective here, which is a critical
step in pursuit of that goal, is to further specify the sensory mechanisms associated with
airway protection disorders in order to advance the clinical management of these patients. In
order to accomplish the objective of this application the study team has identified 3 aims:
First, determine relationship(s) between airway somatosensation, reflex cough and swallowing
function in people with PD, and how these relationships may change with disease progression,
over time. Second, determine whether cortical processing of sensory information is associated
with deficits in reflex cough sensitivity or swallowing function in people with PD, and
third, to determine how the central neural filtering of airway sensory stimuli may relate to
the development of airway protective disorders.

The study team will accomplish these aims in 2 experimental studies. First, the study team
will test the magnitude of respiratory resistive loads, in people with PD across a range of
disease durations, and in a healthy control group. The study team will measure reflex cough,
using a cough-inducing irritant (capsaicin), and swallowing function. The study team will
perform these tests at 3 time-points, spaced 10-14 months apart, in order to determine the
relationships between respiratory sensation, cough sensitivity and effectiveness, and
swallowing function, and how they change with advancing disease duration.

Next the study team will perform electroencephalographic recordings time-locked to paired
respiratory stimuli to determine cortical processing of airway sensory information. The study
team will measure the amplitude and latency of the sensory evoked potential peaks, and
compute ratios of peak amplitude between the first and second paired stimulus in order to
determine the degree of sensory gating. The realization of the proposed aims and studies is
significant because it is a necessary step in our program of research that is expected to
lead to earlier, more accurate identification, as well as targeted interventions for airway
protection deficits in PD.

Completion of this research is systematically important for our goal of maintaining adequate
airway protective function in PD patients; the results are expected to directly impact
reductions in health care costs, morbidity, and mortality related to airway protection
deficits.

Inclusion Criteria:

1. Between the ages of 45 and 85 years

2. Diagnosis of PD, Hoehn and Yahr stages I - IV, by a fellowship trained neurologist
arriving at the diagnosis of PD by applying strict UK brain bank criteria (PD
participants only)

Exclusion Criteria:

1. Neurological disorders other than PD (i.e., stroke, etc.)

2. Difficulty complying due to neuropsychological dysfunction (i.e., severe depression)

3. Allergy to capsaicin or hot peppers

4. History of head or neck cancer

5. History of smoking in the past 5 years

6. Any neurological disorder including PD (Healthy control group only)