Ling Han, MD, PhD, MS

With a unique background of an MD psychiatrist and PhD biostatistician, I provide vital statistical support for research projects at the Yale Program on Aging (POA) and the Veterans Administration (VA) Connecticut Healthcare Systems. These include performing data analyses on funded research projects, consultation on study methodology and statistical plan for grant applications and dissemination, and mentorship for junior faculty and post-doctoral fellows and clinical trainees. In the mean time, I’ve been pursuing medical research of personal interests that are deemed important to benefit aging populations and the society and have contributed to the broader sciences in the geriatric and gerontological fields with more than 100 scientific papers as the primary or a co-author.

My research interests and activities are primarily focusing on the four areas of scientific investigations.

1. Depicting natural courses of cognitive aging, dementia progression and functional disability. In dementia clinics and anti-dementia drug trials, a common “Annual Cognitive Change” (ARC) has since been hopped for as a gold standard for measuring and distinguishing between normal aging and dementia. I collaborated with McGill colleagues and developed a common ARC estimate for Alzheimer’s disease (AD) on the most widely used cognitive screening tool, the Mini Mental State Examination (MMSE), using meta-regression and mixed-effect model [Han et al International Psychogeriatrics 2000]. That paper was selected among top-cited papers in International Psychogeriatrics in 2009 and cited 257 times by 9/30/2025 (http://www.alzheimersinnovation.com). The synthesized ARC estimate has been used in several clinical trials of Alzheimer’s disease. After joining Yale POA, I collaborated with other Yale PEP colleagues and used a group-based trajectory model to “phenotype” cognitive aging among community-dwelling older persons against common functional and institutionalization outcomes defined for AD patients. That study was invited to present as a GSA delegated speech at the 2014 Chinese Congress on Gerontology and Health Industry. One of my biostatistical expertise pertains to the group-based trajectory model. I contributed to several influential papers addressing cognitive and functional aging trajectories (Gill et al, NEJM 2010; Han et al, JGMS 2016). The innovative combination of trajectory modeling and generalized estimating equation from my JGMS 2016 paper has been applied in several subsequent studies [Liu et al JAMDA 2018, Presley et al JGO 2019; Cao et al, JAGS 2021] to “phenotype” aging trajectories to broader functional and healthcare utilization outcomes. My ongoing projects also involve assessment and detection of dementia in emergency department (ED) and development of practical tool to improve early detection of dementia in ED settings [Cohen et al.. J Alz Dement 2025; Cohen et al, JAGS 2025].

2. Applying quasi-experimental design and analytic approaches to mental health disorders, musculoskeletal disorders and other clinical conditions. Confounding by indication and reverse-causality posts major threats to the validity of observational studies of “causal” relationship between medications and other interventions on subsequent health outcomes. To address this important methodological issue, I used “lagged” longitudinal approach and structural equation modeling to delineate complex interrelationship between depression pathology, antidepressant treatment and cognitive impairment [Han et al JGMS 2006; Han et al. J Clin Psychopharm 2011; Han et al. Ann Epidemiol. 2012] In a NIA and AHRQ funded study (PI: Dr. Tinetti), I developed hypertensive exposure intensity based on WHO’s defined daily dose to standardize multiple anti-hypertensive medications over time, and an ordinal propensity score and applied 1:M matching to reduce potential selection bias when examining the effectiveness of antihypertensive treatment. In collaboration with VA and Yale colleagues, I examined and compared several propensity score-based causal methods and proposed to “hybrid” PS matching and IPTW into an optimal approach to enhance the validity when evaluating real-world effectiveness of comprehensive and integrative health (CIH) approaches on chronic pain (Han et al, Pain Med 2019). More recently, I continued pursuing this line of investigation and published two studies of CIH approaches on Pain Care Quality (Han et al, JICM 2023) and on delaying opioid prescriptions [Han et al, J Pain 2025] for musculoskeletal pain among Veterans. The latter study was highlighted in a 2024 October VA Office of Research & Development VA RESEARCH NEWS BRIEFS (https://www.research.va.gov/in_brief.cfm). Currently, I’m providing statistical guidance for a NIH funded R34 grant by adapting recurrent- exposure crossover design [Han et , IJSMR 2016] to EHR data to examine effects of a clinical-decision making tool on palliative care outcome for elder persons.

3. Assessing and evaluating cumulative risk of inappropriate medication use related to polypharmacy in general and anticholinergic medications in particular. With McGill colleagues I developed a clinician-rated anticholinergic score (CR-ACHS) to assess the cognitive risk of anticholinergic drug exposure and demonstrated its dose-response relationship with acute delirium in 2001. Later on in collaboration with VA and Yale colleagues, I updated the CR-ACHS and used it to examine subclinical cognitive dysfunction in older Veterans. Those studies and the CR-ACHS have triggered tremendous research interests and proliferation of a variety of anticholinergic risk scores in the field. The study was also featured on Yale Bulletin and several mass media outlets, including the Tangled Neuron, Medical tribute, and Reuters Heath-Doctors’ Channel. More recent works included examining adverse drug events associated with antibiotic therapy among older adults with advanced cancer [Datta et al Palliat Med 2023] and using an EHR-based retrospective dynamic cohort design and GEE model to assess risk of serious adverse gastrointestinal events among potassium binder users [Holleck et al, J Gen Intern Med 2024].

4. Delineating the heterogeneity, dynamics and socioeconomic determinants of population health and healthcare deliveries and utilizations In the past five years, my research interests have expanded into the social determinants of health. I contributed statistical expertise for several published papers using multi-level model (MLM) [Bernstein et al AJPM Focus. 2023; Feder et al JPSM 2024] and helped investigators in recent grant applications and resubmissions with innovative and rigorous study design and statistical approaches including MLM and resampling-based model validation procedures. Another recent PEP report highly relevant to my current research interest on social determinants of health was a study examining effects of neighborhood disadvantage on life expectancy beyond individual-level demographic and clinical factors [Gill et al JAMA Internal Med 2021]. Currently, I am working on three NIH and VA funded grants that aim at addressing organizational, environmental and socioeconomical barriers to health care delivery and utilizations among older veterans in emergency department, palliative care and community settings [Hwang et al, Acad Emergency Med 2023; Wang et al, Med Care 2024; Feder et al, J Palliat Med 2024].