Continuum, April 2007, Volume 13, Issue 2

Mild cognitive impairment (MCI) has become an important topic for clinical practice and research. MCI refers to a clinical transitional state between the cognitive changes of aging and the earliest clinical features of dementia. Originally, the construct referred to a memory impairment in the setting of preserved nonmemory cognitive performance and functional abilities, but more recently the term has been expanded to include other cognitive domains besides memory. Most of the literature refers to the amnestic form of MCI, which is likely a precursor of clinical Alzheimer's disease. Much research generated in the past decade on MCI indicates that the criteria are available and reliable and that the outcomes of patients are known. Some predictors of progression have been identified, and others are being evaluated. Neuroimaging studies document the intermediate state of brain structural and functional features in patients with MCI, while neuropathologic data confirm transitional pathologic findings. Several randomized clinical trials have been completed recently, and although most are essentially negative, one trial suggested that donepezil might be effective for the treatment of MCI for a limited period of time. Implications of MCI for clinical practice and future research directions are discussed.(C) 2007 American Academy of Neurology

Dementia with Lewy bodies (DLB) took many years to crystallize into a recognizable clinico-pathologic entity. Neuropathologic findings of [alpha]-synuclein lesions in Lewy bodies and neurites correspond to dysfunction of the substantia nigra, and lesions in subcortical, limbic, and cortical regions are associated with cognitive, neuropsychiatric, and motor manifestations, which may be modified by coexisting Alzheimer tangle pathology. Clinical diagnostic criteria combining cognitive decline with features of parkinsonism, fluctuation of cognition, and visual hallucinations have been revised several times. The latest revision recognizes the importance of REM sleep behavior disorder as a clinical feature and bridges DLB and Parkinson's disease with dementia by removing an arbitrary 1-year separation between onset of motor and cognitive symptoms. Neuropathologic diagnosis now assigns a weight to both [alpha]-synuclein and Alzheimer's disease lesions. Treatment remains symptomatic and usually requires sensitive manipulation of a combination of medications to try to stabilize or improve cognitive, behavioral, and motor symptoms while minimizing side effects.(C) 2007 American Academy of Neurology

Cerebrovascular disease is the second leading cause of cognitive impairment in late life, either alone or in combination with Alzheimer's disease. Vascular cognitive impairment (VCI) is a heterogeneous phenotype that may result from a large spectrum of risk factors, blood vessel pathologies, types of vascular brain injury, and regional distribution of infarcts and hemorrhages. Recommendations to harmonize clinical, imaging, pathology, and neuropsychology data have recently been made. No single neuropsychological profile is characteristic of VCI, although dysexecutive function is common and verbal memory tends to be better preserved than in Alzheimer's disease. Compared with Alzheimer's disease, rate of mortality is higher and rate of cognitive decline slower. Silent hyperintensities on MRI, including silent incomplete infarcts and white matter changes, are associated with subtle cognitive impairment and increased risk for stroke, warranting a search for modifiable risk factors. To varying degrees, VCI is potentially preventable by vigilant identification and treatment of vascular risk factors.(C) 2007 American Academy of Neurology

Neuropsychiatric symptoms are a prominent feature of all neurodegenerative dementias. They represent invaluable clinical information for differential diagnosis of patients with cognitive decline. Neuropsychiatric symptoms increase in frequency and severity throughout the course of the disease. They often pose significant psychological burden for the patient and the family and a therapeutic challenge.Continuum Lifelong Learning Neurol 2007;13(2):165-179.(C) 2007 American Academy of Neurology