Research Article: Relationships of hematocrit concentration with dementia from a multiethnic population-based study

David J Roh ^1* Minghua Liu ¹ Kevin Strobino ¹ Stephanie Assuras ¹ Vanessa A Guzman ¹ Bonnie Levin ² Steven L Spitalnik ¹ Tatjana Rundek ² Clinton B. Wright ³ Mitchell Elkind ¹ Jose Gutierrez ^1*

• ¹ Columbia University, New York City, United States
• ² Leonard M. Miller School of Medicine, University of Miami, Miami, Florida, United States
• ³ National Institutes of Health (NIH), Bethesda, Maryland, United States

Objective: Red blood cell (RBC) concentration impacts cerebrovascular disease, yet it is unclear whether RBC concentrations relate to dementia risk, particularly in racially/ethnically diverse cohorts. We investigated whether RBC concentrations associate with incident dementia risk in a diverse population of stroke-free individuals and explored whether cerebral small vessel disease (CSVD) mediates this relationship. Methods: A longitudinal observational analysis was performed using a population-based cohort of stroke-free, older adult participants (>50 years) from the Northern Manhattan Study (NOMAS) enrolled between 2003-2008. Participants received baseline hematocrit testing, MRI neuroimaging, and cognitive assessments at baseline and long-term follow-up. Associations of baseline hematocrit as a categorical variable (low, normal [reference], and high based on laboratory reference levels) with incident dementia were assessed using Cox models adjusting for relevant covariates. Separate analyses investigated whether MRI CSVD mediated these relationships. Results: We studied 1207 NOMAS participants (mean age 71±9 years, 60% female, 66% Hispanic). Mean hematocrit was 41.2% (±3.8) with 16% of participants developing incident dementia. Lower hematocrit associated with increased dementia risk (adjusted hazard ratio 1.81 [1.01-3.23]) after adjusting for age, sex, race/ethnicity, education, APOE status, and comorbidities. High hematocrit was not associated with dementia risk. No interactions by sex or race/ethnicity were seen and baseline CSVD did not mediate relationships between hematocrit and dementia. Conclusions: Low hematocrit associated with dementia risk in our diverse population cohort. However, our study limitations in laboratory and neuroimaging timing in addition to clarifying mechanistic underpinnings for our observations necessitates further work to clarify whether anemia can serve as a trackable, preventable/treatable risk factor for dementia.