Objectives: Acute and subacute cognitive decline, defined collectively as rapid cognitive impairment (RCI), is attributed to diverse disorders and brings great challenges for differential diagnosis. In this study we investigated the RCI patients to determine the underlying causes and the cognitive outcome of the treatable RCI. Patients and Methods: We reviewed medical records of consecutively hospitalized patients (n = 346) with significant and new cognitive dysfunction between January 2014 and December 2015. Based on the duration of their cognitive dysfunction, patients were divided into two groups with the RCI (< 12 months) and the chronic cognitive impairment (CCI, ≥ 12 months), respectively. Etiologies of the RCI and the CCI were analyzed; the cognitive outcomes of the RCI patients with the treatable disorders were assessed in the follow-up visits. Results: Potentially treatable or reversible causes were identified in 134 (72%) of 187 RCI patients and in 34 (21%) of 159 CCI patients. The causes in the 134 (72%) RCI patients were immune/inflammation (50, 37%), infection (30, 22%), vascular diseases (29, 22%), neoplasm (16, 12%), metabolic/toxic disorders (7, 5%), and others (2, 1%). The treatable disorders found in both the RCI and the CCI patients were vascular diseases, autoimmune encephalitis, viral encephalitis, inflammatory demyelinating diseases, Hashimoto encephalopathy, neurosyphilis, hydrocephalus, and Vitamin B12 deficiency. Total 114 RCI patients with the treatable disorders were followed up for 6∼39 (median 21) months. Poor cognitive outcomes were found in 24 (21%) of the 114 followed-up patients, comprising patients with infection (1, 3%), immune/inflammation (12, 25%), vascular diseases (8, 28%), and metabolic/toxic disorders (3, 43%). Conclusions: Treatable or reversible causes are common underlying RCI. Poor outcomes with severe cognitive deficits are considerably present in the treatable RCI patients and result in permanent dementia. © 2019 Elsevier B.V.