Involvement of inflammation in the medial temporal region in the development of agitation in Alzheimer's disease: an in vivo positron emission tomography study

Abstract

Background: The evaluation of 11C-DPA-713 binding using positron emission tomography for quantifying the translocator protein can be a sensitive approach in determining the level of glial activation induced by neuroinflammation. Herein, we aimed to investigate the relationship between regional 11C-DPA713-binding potential (BPND) and neuropsychiatric symptoms (NPS) in amyloid-positive Alzheimer's disease (AD) patients. Methods: Fifteen AD patients were enrolled in this study. Correlations were evaluated between the 11C-DPA713-BPND and Neuropsychiatric Inventory Questionnaire (NPI-Q) scores, including scores in its four domains: agitation, psychosis, affective, and apathy. 11C-DPA713-BPND values were compared between groups with and without the neuropsychiatric symptoms for which a relationship was observed in the abovementioned correlation analysis. Results: A positive correlation was found between the severity of agitation and 11C-DPA713-BPND in the Braak 1–3 area, including the amygdala, hippocampal and parahippocampal regions, and lingual and fusiform areas. An increase in the 11C-DPA713-BPND was observed in AD patients with agitation. We did not find any significant effects of possible confounding factors, such as age, duration of illness, education, gender, Mini-Mental State Examination score, cerebrospinal fluid amyloid β 42/40 ratio, and apolipoprotein E4 positivity, on either the 11C-DPA713-BPND or agitation score. Conclusions: Neuroinflammation in the medial temporal region and its neighbouring area was shown to be associated with the development of agitation symptoms in AD patients. Our findings extend those of previous studies showing an association between some NPS and inflammation, suggesting that immunologically based interventions for agitation can serve as an alternative treatment for dementia.