Towards Timely Alzheimer’s Diagnosis: A Clinical Data-Driven Approach to Biomarker Discovery
Smita Sahay1, Ali Imami1, Abdul Hamoud1, Robert McCullumsmith1, Sinead O'Donovan1
1Department of Neurosciences, The University of Toledo College of Medicine and Life Sciences
Objective:
Determine lab-based biomarkers for early Alzheimer's disease diagnosis based on retrospectively collected critical care medical data.
Background:
Alzheimer’s disease (AD) is a neurodegenerative disorder characterized by a progressive decline in cognitive function and memory. Early symptoms are often non-specific. Traditional diagnosis relies on clinical and cognitive assessments, which are subjective and imprecise. Thus, there is a critical need for objective and reliable biomarkers for the detection of AD. Our study proposes lab-based biomarkers that may aid in the early diagnosis and management of AD.
Design/Methods:
We utilized the MIMIC-IV database that includes critical care data from 40,000 racially and ethnically diverse patients admitted to intensive care units at the Beth Israel Deaconess Medical Center. For each lab (n=1,600+), MIMIC-IV was filtered for patients with a primary diagnosis of AD and age- and sex-matched non-psychiatrically ill control (CTL) patients. Each case was matched to four CTLs. Means and standard deviations were calculated. Welch’s two sample t-test was used to compare means in AD vs. CTL groups. Effect sizes (ES) were calculated to further assess the practical significance of our results.
Results:
Of 477 labs, 51 were significantly different between AD and CTL groups (p<0.05). Of these, 22 had a moderate-large ES (range 0.27-1.16). Of 227 labs exclusive to females, 22 were significantly different between female AD and CTL groups (p<0.05). Of these, 6 had a moderate ES (0.35-0.48). Lastly, of 210 labs exclusive to males, 22 were significantly different between male AD and CTL groups (p<0.05). Of these, 9 had a moderate ES (0.26-0.49).
Conclusions:
Potential lab-based biomarkers for AD were in the following broader diagnostic categories: kidney function (urea nitrogen), cardiovascular (cholesterol), and electrolyte/metabolic balance (chloride, urine glucose). Interestingly, while females and males had overlapping labs, males were distinguished by hematological labs, indicating the importance of considering sex in biomarker analysis for AD.