Major Neurocognitive Disorders

Major neurocognitive disorder is the most common neurodegenerative condition in the world and the leading cause of dependence and disability among older adults worldwide. There are numerous etiologies for major neurocognitive disorder, of which Alzheimer disease (AD) is the most common. Available evidence indicates that the risk factors for major neurocognitive disorder include older age, female sex, lower educational attainment, obesity, and vascular risk factors, including smoking, hypertension, diabetes mellitus, and hyperlipidemia. Certain etiologies for major neurocognitive disorder are heritable, especially those due to AD and frontotemporal lobar degeneration. The pathophysiologic changes associated with the various etiologies of major neurocognitive disorder include neuronal loss, senile plaques, neurofibrillary tangles, vascular pathology, and α-synuclein neuronal inclusions. Major neurocognitive disorder remains a clinical diagnosis with a thorough history, appropriate laboratory tests, and standardized rating scales assisting in determining the etiology and severity of the condition. In older adults, major neurocognitive disorder must be differentiated from depression and delirium as these three conditions may have similar clinical presentations or may coexist. Current data indicate that approximately a third of the cases of major neurocognitive disorder, especially those due to AD, may be prevented by controlling potentially modifiable risk factors, including diabetes, depression, smoking, physical inactivity, midlife hypertension, midlife obesity, and low educational attainment. Currently, the only Food and Drug Administration–approved medications are acetylcholinesterase inhibitors and memantine for use in major neurocognitive disorder due to AD and rivastigmine (an acetylcholinesterase inhibitor) for major neurocognitive disorder due to Parkinson disease. Key words: acetylcholinesterase inhibitors, Alzheimer disease, amyloid precursor protein, frontotemporal lobar degeneration, Lewy body disease, major neurocognitive disorder, memantine, Parkinson disease, tau proteins, vascular disease