The neurobiology of neuropsychiatric syndromes in dementia

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Purpose of reviewNeuropsychiatric disturbances in dementia are prevalent, and research is uncovering their neurobiological correlates.Recent findingsLate-onset depression appears to be associated with Alzheimer's disease pathology at autopsy, and lifetime depression episodes may worsen Alzheimer's disease pathology in the hippocampus. Vascular disease and elevated homocysteine increase risk for both late-onset depression and Alzheimer's disease and may partly mediate their relationship. Monoamine changes are robust finding in Alzheimer's disease and may account for many observed depression symptoms. Risk of psychosis of Alzheimer's disease appears to be increased by several genes also implicated in schizophrenia (e.g., catechol-O-methyltransferase, neuregulin-1). Psychosis in dementia with Lewy bodies appears to be related to cholinergic deficits. Alzheimer's disease is associated with changes in the circadian sleep–wake cycles, including decreased night-time melatonin. Sleep apnea may be related to apolipoprotein E genotype and impact cognition in Alzheimer's disease. Rapid eye movement sleep behavior disorder is intricately related to synucleinopathies, such as dementia with Lewy bodies, but synuclein changes may not totally explain this relationship.SummaryNeuropsychiatric disturbances are a core feature of dementia and worsen many clinical outcomes. Among the most validated syndromes are depression, psychosis, and sleep disturbance of Alzheimer's disease. Neuropathology, neuroimaging, and genetic studies increasingly provide insight into the origins of these psychiatric symptoms in dementia.

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