Mortality of early-onset dementia in a Thai cohort at Siriraj Hospital, Thailand

Vorapun Senanarong¹, Chatchawan Rattanabannakit¹, Natthamon Wongkom¹, Pathitta Thitivichienlerd¹, Wisarut Nanthasi¹, Paphawadee Phoyoo¹, Saowalak Hunnangkul², Yudthaphon Vichianin³, Phillippus Scheltens⁴.

¹Division of Neurology, Department of Medicine, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand

²Department of Health Research and Development, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand

³Department of Radiological Technology, Faculty of Medical Technology, Mahidol University, Bangkok, Thailand

⁴Head Director Dementia Fund & Partner EQT Life Sciences, the Netherlands

Corresponding authors: Vorapan Senanarong, Department of Medicine, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand. Tel: +6624197105. Email: vorapan.sen@mahidol.ac.th

Early-onset dementia (EOD), defined as onset before age 65, significantly increases mortality risk compared to the general population

Objectives: We followed EOD cohort to determine the mortality rate. We investigated biological and characteristically mortality risk factor of EOD cohort.

Method:  151individuals with EOD at EOD clinic and memory clinic at Siriraj hospital were follow up for 15 years. Baseline subject characteristics and blood (68) or cerebrospinal fluid (CSF) (82) biomarkers were recorded. MRI brain volume analysis had only performed only 59 subjects, the rest were waiting for the results.

Results: Among 151EOD patients, 94 were Alzheimer disease (AD) dementia, 57 were non-AD dementia.  After the diagnosis, 21 was transferred to manage at hospitals where the patients live. Mean follow up time was 8.13 years.  At the last hospital visit or telephone follow up call in 2025, 98 are alive, and 53 were dead (35.09%). Mean survival after the diagnosis was 8.13 years. Mean survival time for AD group was 14.03 years while mean survival time for non-AD group was 10.99 years (p=0.101).  There were no statistically significant differences between those who are alive and those who were dead in age at onset, gender, duration after the diagnosis, ApoE4 status, AD or non-AD diagnosis, baseline (BL) Thai mental state exam (TMSE), BL neuropsychiatric problems, BL blood pTau217, BL blood AB42/40, and interim brain volume analysis. Those who presenting with social history issues (namely having a positive familial history of YOD, fear of having dementia, financial problems, jobloss, relationship problems, work problems, or worries from caregivers) have ORs of 2.94 (p=0.047) for death risk. There were significant difference at BL between the alive group and the dead group in blood BL CSF AB42 (p=0.008, OR=0.996), CSF total Tau(p=0.041, OR=0.001), BL activity of daily living scale scores(ADL)(p=0.007,OR=1.067), BL functional assessment questionnaire(FAQ) (p=0.005,OR=1.057), BL verbal fluency from ACE iii R (p=0.020, OR=0.817), TMSE at the 5^th year follow up (p=0.017, OR=0.925). There was a trend of BL GFAP to be mortality risk (p=0.051, OR=1.006).  Having family history of either EOD or LOD (Goldman score 1 or 2 or 3 or 3.5 vs 4) is also indicate mortality risk (p=0.002, OR=3.554). Limitations of our study are small cohort and single center. Multicenter study with data exploring health disparity should be included in future study.

Conclusion: Our study revealed that verbal fluency, clinical function, neuroinflammation, and global cognition at the 5^th year were mortality risk in our EOD cohort.