shortness of breath and worsening cognition

The patient is a 79-year-old African American man presenting with shortness of breath and
progressive worsening cognition. He had multiple prior admissions for congestive heart failure
exacerbations.

Beginning in 2003, the patient became increasingly confused and absent minded, misplacing
objects, and forgetting plans and conversations. The symptoms progressed slowly over the
years. In 2005, he was diagnosed with amnestic mild cognitive impairment (MCI) with
cognitive dysfunction from medications and medical illness. At that time had a score of 24/30
on the Mini Mental Status Examination. In 2006, he had an episode of transient ischemic attack-
like symptoms. A head CT was performed that suggested mild-moderate hypoattenuation of the
perivascular white matter and a small, old left lacunar basal ganglia infarct. Repeat Mini Mental
Status Examination score was 22/30 at this time. He was enrolled in a study at the Alzheimer's
Disease Research Center at The Johns Hopkins University in 2005. His family noted that he'd
lost 25 pounds in the last year due to an apparent lack of appetite and difficulty swallowing food.
They noted he would chew food slowly then be unable to swallow and spit out food. This
occurred with solids and liquids. He denied pain with swallowing. They also noted that he
seemed to stare forward even when the TV was playing or grandchildren shouted his name.

His past medical history was significant for congestive heart failure, idiopathic pulmonary
fibrosis (no improvement with prednisone), chronic urinary retention, GERD, arthritis, and gout.
He had a family history remarkable for Alzheimer's Disease.

Amnestic cognitive impairment
Cardiomyopathy
Usual interstitial pneumonia/idiopathic pulmonary fibrosis
Neurogenic bladder
Penile implant with pump
Gout
Gastroesophageal reflux disease
Osteoarthritis

Alzheimer's disease, sister
Lung cancer, two bothers

The patient was a retired physicist with 5-pack year history of smoking, quite 45 years ago.
Occupational cesium-164 radiation exposure. No alcohol or illicit drug abuse.

Home oxygen 2L/min, Carvedilol 6.25 twice a day; Lasix 40 mg daily, Hydralazine 50 three
times a day; Imdur 30 a day; Protonix 40 daily; Allopurinol 300 mg a day; Folate 1 mg a day;
Colace 100 by mouth twice a day; Dapsone 100 a day; albuterol/ipatroprium mdi as needed

Penicillin

Lack of ambulation (was walking with a cane, then slowly with a walker but has had recent
periods where he could not get out of bed; walking problems have been attributed to chronic hip
arthritis in the past), bilateral hand tremors, worsening cognition, confusion, dyspnea. 25 pound
weight loss in last year due to decreased appetite and difficulty swallowing food.

Weight: 90 kg Height: 185 cm T: 964 BP: 139/90 P: 110 irregular R: 18 O2 Sat: 88%
             (room air)
General: African-American male, dyspneic, confused, difficult to examine because of lack of
            attention and poor cognition
HEENT: Slightly elevated jugular venous pressure. Sclera anicteric. Extraocular muscles
            difficult to examine because of cooperation, probably intact. Oropharynx was clear with
             no thrush or blood blisters or lesions. No palpable adenopathy in the cervical,
            supraclavicular, axillary areas.
CV: Tachycardia, systolic murmur III/VI.
Lungs: Bilateral paninspiratory crackles.
Abdomen: Normal bowel sounds, non-tender, non-distended. No hepatosplenomegaly.
Extremities: +1 lower extremity edema, minimal cyanosis, no clubbing. Pulses 2+.
Neuro: Poor orientation, poor effort, limited focus. 3/5 strength in all extremities. Has difficulty
            following conversation or commands. Frequent confusion. Reflexes and strength appear
            symmetric. Some limb rigidity and resting tremor of both hands; no prominent axial
            rigidity. Unable to assess gait or coordination.

White count of 4,070, hemoglobin 11.1, hematocrit 37.5, MCV 94.1, platelet count 168,000.
differential 74 polys, 16% lymphs, 6% monocytes, 1% eosinophils.

Chemistry panel showed: sodium 130, potassium 5.8, BUN 30, creatinine 2.2. Glucose 97.
AST /ALT 51/53. Troponin < 0.6. PT/aPTT normal. Urinalysis was negative for leukocyte
esterase. Microscopic examination revealed 1-2 white cells and only a few bacteria. Blood and
urine cultures are negative.

Head CT shows patchy hypoattenuation in the periventricular white matter without associated
mass effect, most likely reflecting small vessel ischemic change. No acute intracranial
abnormality. The studies from both 4/2/05 and 6/20/06 showed similar findings (Image 1)

Admission chest X-ray studies suggested either pulmonary congestion, pneumonia, or worsening
fibrosis. On EKG he was found to be in atrial fibrillation and the patient was started on heparin
treatment as prophylaxis against emboli. Lower extremity ultrasound revealed non-occlusive
thrombi in the left common femoral, greater saphenous, and profunda femoris veins. The
patient's respiratory status continued to deteriorate over the next several days as evidenced by
increasing oxygen requirements and increased respiratory rate, acutely rising creatinine, and
markedly decreased mentation. The patient was DNR/DNI. The patient experienced an acute
episode of cardiac arrhythmia and expired.

What is the most likely cause of this patient's progressive cognitive decline?

What are "proteinopathies" and how do they relate to different clinical cognitive syndromes?