Contribution of amyloid and putative Lewy body pathologies in neuropsychiatric symptoms

Objectives Neuropsychiatric symptom could be useful for detecting patients with prodromal dementia. Similarities and differences in the NPSs between preclinical/prodromal Alzheimer's disease (AD) and prodromal Parkinson's disease dementia (PDD)/Dementia with Lewy bodies (DLB) may exist. This study aimed to compare the NPSs between preclinical/prodromal AD and prodromal PDD/DLB. Methods One hundred and three participants without dementia aged ≥50 years were included in this study. The mild behavioral impairment (MBI) total score and the MBI scores for each domain were calculated using the neuropsychiatric inventory questionnaire score. Participants were divided into five groups based on the clinical diagnosis by neurologists or psychiatrists in each institution based on the results of the amyloid positron emission tomography and dopamine transporter single photon emission computed tomography (DAT‐SPECT): Group 1: amyloid‐positive and abnormal DAT‐SPECT, Group 2: amyloid‐negative and abnormal DAT‐SPECT, Group 3: amyloid‐positive and normal DAT‐SPECT, Group 4: mild cognitive impairment unlikely due to AD with normal DAT‐SPECT, and Group 5: cognitively normal with amyloid‐negative and normal DAT‐SPECT. Results The MBI abnormal perception or thought content scores were significantly higher in Group 1 than Group 5 (Bonferroni‐corrected p = 0.012). The MBI total score (Bonferroni‐corrected p = 0.011) and MBI impulse dyscontrol score (Bonferroni‐corrected p = 0.033) in Group 4 were significantly higher than those in Group 5. Conclusion The presence of both amyloid and putative Lewy body pathologies may be associated with psychotic symptoms. Key Points The presence of both amyloid and putative Lewy body pathologies may be associated with psychotic symptoms. Putative Lewy body pathologies may be linked to anxiety and mood symptoms. Diseases unrelated to amyloid or dopamine transporter single photon emission computed tomography (DAT‐SPECT), such as tauopathy and TDP43 pathology, may be involved in agitation, impulsivity, anxiety, and mood symptoms.