Background/Objectives:Psychosis (delusions or hallucinations) is a common clinical feature in patients with Alzheimer’s disease (AD), and is estimated to affect up to half of this patient population. Psychosis is associated with increased cognitive and functional decline as well as greater caregiver burden. However, lack of understanding of the pathobiological mechanisms behind psychosis limits our ability to manage and treat these symptoms. The current literature is mixed, with some studies showing a correlation between psychosis and Alzheimer pathology, while others find no such association. Using data from the large National Alzheimer’s Coordinating Center (NACC) database, we aimed to determine the demographic, clinical, and neuropathological features associated with psychotic symptoms, separated into delusions and/or hallucinations, in patients who were clinically or neuropathologically diagnosed with AD.Methods:All data were obtained from the NACC database. Our sample of consisted of 1073 subjects broken down into: 1) 890 clinically diagnosed AD (cAD) patients with neuro-pathology data, and 2) 728 neuropathologically confirmed AD (npAD) patients based on the Consortium to Establish a Registry for Alzheimer’s Disease (CERAD) criteria of “definite” AD with any clinical diagnosis. The two groups overlapped, but each was reviewed separately. Delusions and hallucinations were identified by the delusional and hallucinatory sub-scores of the Neuropsychiatric Inventory (NPI-Q), respectively.Results:Over one-third of our AD subjects (cAD and npAD) had psychotic symptom(s) during the course of their illness. There were no apparent differences between patients with psychosis (cAD+P n=307; npAD+P n=271) and without psychosis (cAD-P n=583; npAD-P n=457), defined globally, on functional (FAQ) and cognitive outcomes (MMSE, global CDR). However, further breakdown by psychotic symptoms showed that patients with hallucinations (cAD+H n=57; npAD+H n=52) were more severely cognitively and functionally impaired at the last visit prior to death, while patients with delusions (cAD+D n=164; npAD+D n=140) were less impaired than non-psychotic patients, consistent across both cAD and npAD groups. We found that, in the cAD group, psychosis was associated with greater levels of plaques and tangles, but this association was not present in the npAD group. Lewy body pathology, sub-cortical arteriosclerotic leukoencephalopathy (SAL) and vascular risk factors, particularly a history of hypertension and diabetes, were associated with psychotic symptoms in both the cAD and npAD groups.Conclusion:Markers of AD pathology (plaques, tangles) are associated with psychotic symptoms in clinically diagnosed AD patients. However, in neuropathologically confirmed AD patients, AD pathology does not correlate with psychotic symptoms, suggesting that the association in the clinical group is driven by misdiagnosis. Instead, in the neuropathologically confirmed AD group, psychosis is associated with Lewy body pathology, vascular risk factors, and vascular pathology. The findings suggest that modifiable factors such as vascular pathology may play a role in psychosis in AD.
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Jan 1, 2018
Open Access
Jeremy Chien + 1