Acute Stroke: Given the sudden onset of lethargy, a stroke is a highly plausible cause. Strokes can present with a wide range of symptoms, including sudden lethargy or altered mental status, especially in the elderly.

Severe Infection (Sepsis): Infections can cause significant alterations in mental status, particularly in older adults. The body's response to a severe infection can lead to sepsis, which may manifest as lethargy among other symptoms.
Metabolic Disorders (e.g., Hypoglycemia, Hyperglycemia): Both low and high blood sugar levels can cause lethargy. In diabetic patients or those with other metabolic disorders, these conditions are particularly relevant.
Acute Kidney Injury or Uremia: Buildup of toxins due to kidney failure can lead to altered mental status, including lethargy.
Cardiac Conditions (e.g., Myocardial Infarction, Heart Failure): Reduced cardiac output can lead to decreased perfusion of the brain, resulting in lethargy.

Subarachnoid Hemorrhage: Although less common, a subarachnoid hemorrhage can present with sudden onset of lethargy and is a medical emergency that requires immediate attention.
Status Epilepticus (especially non-convulsive): Prolonged seizure activity without overt convulsions can manifest as lethargy or altered mental status.
Meningitis or Encephalitis: Infections of the meninges or brain can cause sudden lethargy and are critical to diagnose and treat promptly.
Carbon Monoxide Poisoning: This can cause nonspecific symptoms, including lethargy, and is crucial to identify due to its potential for severe outcomes if not treated.

Hashimoto's Encephalopathy: A rare condition associated with Hashimoto's thyroiditis, characterized by altered mental status, including lethargy.
Whipple's Disease: A systemic bacterial infection that can affect the brain, leading to symptoms such as lethargy, though it is exceedingly rare.
Creutzfeldt-Jakob Disease: A rare, degenerative, fatal brain disorder that can present with rapid deterioration of mental status, including lethargy.