Abstract
Psychosis in Alzheimer’s disease (AD) represents a distinct disease subtype with a more rapid progression of illness evidenced by an increased velocity of cognitive decline and a hastened mortality. Previous biomarker and post-mortem studies have implicated tau neuropathology as a possible mediator of the accelerated decline in AD psychosis. Tau positron emission tomography (PET) neuroimaging provides the opportunity to evaluate tau pathology in-vivo, so that clinical symptomatology can be correlated with disease pathology. [18F]-AV1451 (Flortaucipir) is a PET ligand with high affinity for insoluble paired-helical filaments (PHFs) of hyperphosphorylated tau. In order to determine whether the development of psychosis and worsened prognosis in AD is associated with an increased burden of tau pathology that can be identified with tau imaging, we identified subjects within the Alzheimer’s disease neuroimaging initiative (ADNI) who had [18F]-AV1451 imaging at baseline and became psychotic over the course of the study (N = 17) and matched them 1:3 for gender, age, and education to subjects who had [18F]-AV1451 imaging at baseline and did not become psychotic (N = 50). We compared baseline [18F]-AV1451 retention, in addition to cognitive and functional baseline and longitudinal change, in those who became psychotic over the course of participation in ADNI with those who did not. Results suggest that increases in tau pathology in frontal, medial temporal, and occipital cortices, visualized with [18F]-AV1451 binding, are associated with psychosis and a more rapid cognitive and functional decline.
Highlights
Psychosis occurring over the course of Alzheimer’s disease (AD), comprising the idiopathic development of fixed false beliefs or disturbances of perception [1], represents a distinct phenotype [2] that is a harbinger of an accelerated velocity of cognitive and functional decline leading to hastened mortality [3,4,5,6,7,8]
In order to determine whether the development of psychosis and worsened prognosis in AD is associated with an increased burden of tau pathology that can be identified with tau imaging, we compared baseline [18F]-AV1451 retention together with cognitive and functional decline in those who became psychotic over the course of participation in Alzheimer’s Disease Neuroimaging Initiative (ADNI) with those who did not
The primary goal of ADNI has been to test whether serial magnetic resonance imaging (MRI), positron emission tomography (PET), other biological markers, and clinical and neuropsychological assessment can be combined to measure the progression of mild cognitive impairment (MCI) and early Alzheimer’s disease (AD)
Summary
Psychosis occurring over the course of Alzheimer’s disease (AD), comprising the idiopathic development of fixed false beliefs or disturbances of perception [1], represents a distinct phenotype [2] that is a harbinger of an accelerated velocity of cognitive and functional decline leading to hastened mortality [3,4,5,6,7,8]. In post-mortem studies, increased tangle pathology [18,19,20] and an excess of phosphorylated tau [21, 22] have been associated with a history of psychosis. Taken together, these studies suggest that an excess burden of tau pathology may be a risk factor for the development of psychosis, and may partially explain its more rapid cognitive decline. No published studies have utilized tau neuroimaging to study the in-vivo relationship between tau pathology and the development of psychotic symptoms in AD. Published results from ADNI suggest that [18F]-AV1451 retention discriminates AD from mild cognitive impairment (MCI) and healthy controls, and correlates with CSF tau biomarkers [26]
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