Two observational cohort studies revealed that altered levels of hemoglobin and liver function markers were associated with Alzheimer disease (AD). The first study included 12,305 participants without dementia of the population-based Dutch cohort (mean age 64.6 years, 57.7% women). During a mean follow-up of 12.1 years, 1,520 individuals developed dementia, 1,194 of whom had AD. Both low and high hemoglobin levels were associated with increased dementia risk (hazard ratio lowest vs middle quintile 1.29; highest vs middle quintile 1.20). Overall prevalence of anemia was 6.1%, and anemia was associated with a 34% increased risk of dementia and 41% for AD. Among individuals without dementia with brain MRI, similar U-shaped associations were seen of hemoglobin with white matter hyperintensity volume, and structural connectivity (diffusivity), but not with presence of cortical and lacunar infarcts. Cerebral microbleeds were more common with anemia. Hemoglobin levels inversely correlated to cerebral perfusion. The other cohort study of 1581 participants (697 women; mean age 73.4 years) included 407 cognitively normal older adults, 20 with significant memory concern, 298 with early mild cognitive impairment, 544 with late mild cognitive impairment, and 312 with AD. Elevated aspartate aminotransferase to alanine aminotransferase ratios were associated with diagnosis of AD, poor cognition, lower cerebrospinal fluid levels of amyloid-β 1-42, increased amyloid-β deposition, higher cerebrospinal fluid levels of phosphorylated tau and total tau, and reduced brain glucose metabolism. Lower levels of alanine aminotransferase were associated with increased amyloid-β deposition, reduced brain glucose metabolism, greater brain atrophy, diagnosis of AD, and poor cognition. The findings suggest the involvement of hemoglobin as well as metabolic disturbances in the pathophysiology of AD. Source: https://n.neurology.org/; https://jamanetwork.com/
