Earlier identification of cognitive impairment may reduce patient and caregiver morbidity. To systematically review the diagnostic accuracy of brief cognitive screening instruments and the benefits and harms of pharmacologic and nonpharmacologic interventions for early cognitive impairment. MEDLINE, PsycINFO, and the Cochrane Central Register of Controlled Trials through December 2012; systematic reviews; clinical trial registries; and experts. English-language studies of fair to good quality, primary care–feasible screening instruments, and treatments aimed at persons with mild cognitive impairment or mild to moderate dementia. Dual quality assessment and abstraction of relevant study details. The Mini-Mental State Examination (k = 25) is the most thoroughly studied instrument but is not available for use without cost. Publicly available instruments with adequate test performance to detect dementia include the Clock Drawing Test (k = 7), Mini-Cog (k = 4), Memory Impairment Screen (k = 5), Abbreviated Mental Test (k = 4), Short Portable Mental Status Questionnaire (k = 4), Free and Cued Selective Reminding Test (k = 2), 7-Minute Screen (k = 2), and Informant Questionnaire on Cognitive Decline in the Elderly (k = 5). Medications approved by the U.S. Food and Drug Administration for Alzheimer disease (k = 58) and caregiver interventions (k = 59) show a small benefit of uncertain clinical importance for patients and their caregivers. Small benefits are also limited by common adverse effects of acetylcholinesterase inhibitors and limited availability of complex caregiver interventions. Although promising, cognitive stimulation (k = 6) and exercise (k = 10) have limited evidence to support their use in persons with mild to moderate dementia or mild cognitive impairment. Limited studies in persons with dementia other than Alzheimer disease and sparse reporting of important health outcomes. Brief instruments to screen for cognitive impairment can adequately detect dementia, but there is no empirical evidence that screening improves decision making. Whether interventions for patients or their caregivers have a clinically significant effect in persons with earlier detected cognitive impairment is still unclear. Agency for Healthcare Research and Quality.