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Dementia-related psychosis (DRP) is prevalent across dementias and typically manifests as delusions and/or hallucinations. The mechanisms underlying psychosis in dementia are unknown; however, neurobiological and pharmacological evidence has implicated multiple signaling pathways and brain regions. Despite differences in dementia pathology, the neurobiology underlying psychosis appears to involve dysregulation of a cortical and limbic pathway involving serotonergic, gamma-aminobutyric acid ergic, glutamatergic, and dopaminergic signaling. Thus, an imbalance in cortical and mesolimbic excitatory tone may drive symptoms of psychosis. Delusions and hallucinations may result from (1) hyperactivation of pyramidal neurons within the visual cortex, causing visual hallucinations and (2) hyperactivation of the mesolimbic pathway, causing both delusions and hallucinations. Modulation of the 5-HT2A receptor may mitigate hyperactivity at both psychosis-associated pathways. Pimavanserin, an atypical antipsychotic, is a selective serotonin inverse agonist/antagonist at 5-HT2A receptors. Pimavanserin may prove beneficial in treating the hallucinations and delusions of DRP without worsening cognitive or motor function.

To estimate regional Alzheimer disease (AD) pathology burden clinically, analysis methods that enable tracking brain amyloid or tau positron emission tomography (PET) with magnetic resonance imaging (MRI) measures are needed. We therefore developed a robust MRI analysis method to identify brain regions that correlate linearly with regional amyloid burden in congruent PET images. This method was designed to reduce data variance and improve the sensitivity of the detection of cortical thickness–amyloid correlation by using whole brain modeling, nonlinear image coregistration, and partial volume correction. Using this method, a cross-sectional analysis of 75 tertiary memory clinic AD patients was performed to test our hypothesis that regional amyloid burden and cortical thickness are inversely correlated in medial temporal neocortical regions. Medial temporal cortical thicknesses were not correlated with their regional amyloid burden, whereas cortical thicknesses in the lateral temporal, lateral parietal, and frontal regions were inversely correlated with amyloid burden. This study demonstrates the robustness of our technique combining whole brain modeling, nonlinear image coregistration, and partial volume correction to track the differential correlation between regional amyloid burden and cortical thinning in specific brain regions. This method could be used with amyloid and tau PET to assess corresponding cortical thickness changes.

Vascular dementia (VaD) is the second most common cause of dementia in the elderly. Neuropsychologically, VaD has been characterized traditionally as having a "patchy" pattern of cognitive deficits. Newly developed diagnostic criteria for VaD suggest that this "patchy" pattern is associated with one type of VaD-multiple cortical infarctions, and that several additional subtypes of VaD exist, each featuring a characteristic pattern of neuropsychological deficits. Strategic infarct dementias have unique features that reflect the specific brain region affected. Lacunar state and Binswanger's disease produce subcortical dementia with disproportionate executive dysfunction. The profile of neuropsychological disturbances observed in VaD patients provides important insight into the localization and pathophysiology of the underlying cerebrovascular disease.