Exploring the Relationship Between Brain Structural and Antipsychotic Drug Dosage in BPSD
Poster No:
269
Submission Type:
Abstract Submission
Authors:
Bo Hong1, Tianli Tao2, Han Zhang2, jianhua chen1, Ling Yue1
Institutions:
1Shanghai Mental Health Center, Shanghai Jiao Tong University School of Medicine, Shanghai, Shanghai, 2School of Biomedical Engineering, ShanghaiTech University, Shanghai, Shanghai
First Author:
Bo Hong
Shanghai Mental Health Center, Shanghai Jiao Tong University School of Medicine
Shanghai, Shanghai
Shanghai Mental Health Center, Shanghai Jiao Tong University School of Medicine
Shanghai, Shanghai
Co-Author(s):
jianhua chen
Shanghai Mental Health Center, Shanghai Jiao Tong University School of Medicine
Shanghai, Shanghai
Shanghai Mental Health Center, Shanghai Jiao Tong University School of Medicine
Shanghai, Shanghai
Ling Yue
Shanghai Mental Health Center, Shanghai Jiao Tong University School of Medicine
Shanghai, Shanghai
Shanghai Mental Health Center, Shanghai Jiao Tong University School of Medicine
Shanghai, Shanghai
Introduction:
Behavioral and psychological symptoms of dementia (BPSD), such as aggression, agitation, anxiety afflict over 75% of patients with Alzheimer disease (AD) (Halpern Rachel, 2019) and impose a high burden on caregivers and the patient's family (Jia J, 2018). Given that psychotropic medications are broadly prescribed among BPSD, the safety of antipsychotic drugs has always been a concern (Kuehn B.M., 2005 & Maust D.T., 2015). Furthermore, for different patients with comparative severity of BPSD, there may be significant variations in the dosages of antipsychotic drugs required. However, the objective indicators, which can be utilized for evaluating drug dosage are still lacking. Since BPSD patients may have altered brain structure, it is highly desired to investigate relationship between the brain structural alteration and the final effective antipsychotic drug dosage for BPSD patients towards precision medicine.
Methods:
This study focuses on AD patients who are outpatient or hospitalized in the geriatric psychiatry department at the Shanghai Mental Health Center, China. Baseline general demographic data were collected from the patients. Their cognitive function was evaluated using the Mini Mental State Scale (MMSE) and the behavioral and psychological symptoms were evaluated by the Neuropsychiatric Inventory (NPI). 3D T1w brain structural MRI data were acquired and processed with Freesurfer 7.0, resulting in 68 cortical thickness and 16 subcortical regions of interest (ROIs) based on the Desikan-Killiany atlas (Desikan et al., 2006) and the Automatic Segmentation of Subcortical Structures (Fischl, 2002), respectively. All patients underwent standardized clinical treatment (with or without concomitant antipsychotic drugs) and were followed up until BPSD remission. Drug treatment procedures (including drug types and doses) were recorded, where the antipsychotic drugs were converted using a defined daily dose (DDD) method to obtain the final daily dose (Leucht S., 2016). We divided the patients into three groups: DDDs=0, 0<DDDs<0.3, and DDDs≥0.3, representing a non-antipsychotic group (NAP), a low-dose group (LAP), and a high-dose group (HAP). Region-wise comparisons on cortical thickness and sub-cortical volume were conducted across different groups. Finally, we investigated the relationship between the altered brain regions and the DDDs.
Results:
A total of 86 AD patients who met the ICD-10 diagnostic criteria were enrolled (NAP, n=28, LAP, n=26, HAP, n= 32). Among the three groups, NAP group showed less NPI score than LAP and HAP, while no difference was observed in age, gender, education level and MMSE score (Tab. 1). ANCOVA analysis on brain region-wise cortical thickness measures, after controlling age, gender, education level, showed significant differences in the thickness at the left pars orbitalis (F=3.277, p=0.003) and the volume of left thalamus (F=4.279, p<0.001) among three groups. Post hoc analysis indicated that the HAP group had thinner cortex in the left pars orbitalis compared to the NAP group (Fig 2A). Ordinal logistic regression analysis revealed that NPI (p=0.014) and cortical thickness at the left pars orbitalis (p=0.037) were independent predictors of antipsychotic drug dosage. Further association analysis between cortical thickness of the left pars orbitalis and DDDs revealed a significant negative correlation (r=-0.229, p=0.04) even after adjusting for gender, age, education level, MMSE and NPI score (Fig 2B).
Conclusions:
This study provides first-ever evidence that brain anatomical changes may serve as valuable biomarkers in prediction of antipsychotic drug dosage for patients with BPSD. The result has significant implications for optimizing clinical management strategies and offers insights into the intricate neuropathological mechanisms of BPSD.
Disorders of the Nervous System:
Neurodegenerative/ Late Life (eg. Parkinson’s, Alzheimer’s) 1
Psychiatric (eg. Depression, Anxiety, Schizophrenia)
Novel Imaging Acquisition Methods:
Anatomical MRI 2
Keywords:
Aging
MRI
Psychiatric
STRUCTURAL MRI
Treatment
Other - drug dose
1|2Indicates the priority used for review
Provide references using author date format
Desikan, R. S. (2006), ‘An automated labeling system for subdividing the human cerebral cortex on MRI scans into gyral based regions of interest’, NeuroImage, vol. 31, no. 3, pp. 968–980.
Fischl, Bruce, et al. (2002), ‘Whole brain segmentation: Automated labeling of neuroanatomical structures in the human brain’ Neuron, vol. 33, no. 3, pp. 341–355.
Halpern Rachel. (2019), ‘Using electronic health records to estimate the prevalence of agitation in Alzheimer disease/dementia’, International Journal of Geriatric Psychiatry, vol. 34, no. 3, pp. 420-431.
Jia J. (2018), ‘The cost of Alzheimer's disease in China and re-estimation of costs worldwide’, Alzheimer’s & Dementia, vol. 14, no. 4, pp. 483-491.
Kuehn B.M.(2005), ‘FDA warns antipsychotic drugs may be risky for elderly’, JAMA, vol. 293, no. 20, pp. 2462-2462.
Leucht S.(2016), ‘Dose Equivalents for Antipsychotic Drugs: The DDD Method’, Schizophrenia Bulletin, vol. 42, no. 1, pp. 90-94.
Maust D.T.(2015), ‘Antipsychotics, Other Psychotropics, and the Risk of Death in Patients With Dementia: Number Needed to Harm’, JAMA Psychiatry, vol. 72, no. 5, pp. 438-445.
Acknowledgement
This work is partially supported by the STI 2030–Major Projects (2022ZD0213100, 2022ZD0209000, and 2021ZD0200516), Shanghai Pilot Program for Basic Research–Chinese Academy of Science, Shanghai Branch (JCYJ-SHFY-2022-014), the Shanghai Science and Technology Committee (20Y11906800), and Shenzhen Science and Technology Program (No. KCXFZ20211020163408012).