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When assessing patients with acute or chronic changes in cognition, two interrelated questions should be pursued during the history and examination:

  • Is the presentation focal or global?

  • Is the problem arising from primary brain pathology or a systemic process that is affecting the brain?

Focal deficits suggest focal brain pathology (e.g., stroke, tumor, abscess), although focal findings can occur with systemic disease in the absence of focal central nervous system pathology (e.g., focal seizures or hemichorea caused by hyperglycemia or aphasia caused by cefepime toxicity). Global dysfunction is generally due to systemic pathology affecting the brain, although diffuse intrinsic brain pathology can also cause a global encephalopathy (e.g., multiple strokes, multiple metastases, a diffuse infiltrating malignant lesion, acute disseminated encephalomyelitis).

Focal cognitive deficits may give the initial misleading impression that there is a global encephalopathy. Examples of focal deficits that can initially appear to be global encephalopathic states unless examined in detail include Wernicke’s aphasia producing lack of comprehension and abnormal speech, and transient global amnesia causing isolated short-term memory impairment. On the other hand, global cognitive dysfunction may make it challenging to elicit coexisting focal deficits on examination since a core feature of global cognitive dysfunction is inattention, which can make it difficult to examine cognitive functions that rely on attention such as language, memory, and ability to follow commands.

Delirium refers to acute altered mental status (developing over hours to days), and dementia refers to chronic development of cognitive dysfunction (over years). Rapidly progressive dementia describes subacute development of cognitive dysfunction (over weeks to months).


Delirium is characterized by acute onset of altered mental status with fluctuations in both symptoms and level of arousal. Delirium causes a global encephalopathy, with inattention as the core feature. The differential diagnosis for acutely altered mental status is as broad as the differential diagnosis for any condition in medicine. Delirium can be caused by intrinsic brain pathology (see “Neurologic Causes of Acutely Altered Mental Status” below), systemic disease affecting the brain (e.g., renal or hepatic failure, systemic infections, electrolyte disturbances, hypoglycemia or hyperglycemia, hyperammonemia, hypothyroidism or hyperthyroidism), medications, toxins, drugs, or drug withdrawal. Primary psychiatric etiologies may also be causative or contributory. Although new changes in cognition or personality in patients with psychiatric disease may be due to the underlying psychiatric disease, potential reversible medical causes should be sought.

Patients who are elderly or have baseline neurologic dysfunction (e.g., dementia) are at increased risk of delirium due to any of the above etiologies (as well as due to the disorienting environment of the hospital if the patient is hospitalized).

Neurologic Causes of Acutely Altered Mental Status

Neurologic etiologies of acute-onset altered mental status include seizures, stroke and cerebrovascular disease, CNS infections, and transient global amnesia.

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