Associations of anemia and cardiovascular disease with longitudinal changes in brain MRI markers and cognitive decline in older adults: A cohort study

Abstract Background Anemia and cardiovascular disease (CVD) are two prevalent chronic conditions causing cerebral hypoxia in older adults. Although anemia and CVD often coexist in older people and potentially share underlying mechanisms, the independent effects of these two diseases with cognitive decline are largely unknown. The objective of this cohort study is to investigate the independent associations of anemia and CVD with cognitive decline in older adults, and further explore their associations with changes in MRI markers of brain aging using longitudinal MRI data. Method This cohort study used data from 2244 dementia‐ and stroke‐free participants in the population‐based Swedish National study on Aging and Care in Kungsholmen (age ≥60 years, female 62%). Participants were regularly followed from 2001‐2004 (baseline) through 2013‐2016. Anemia (WHO criteria) and CVD were determined at baseline. Cognitive function was assessed using a neuropsychological test battery across 12 years. A subset of participants (N = 503) underwent brain MRI examinations at baseline, and 327undertook follow‐up MRI scans after 3 and/or 6 years. Brain volumetric measures and markers of cerebral small vessel disease (cSVD) were assessed following standard methods. The associations of anemia or/and CVD with cognitive decline and changes in brain volume and cSVD markers were investigated using linear mixed‐effects models, while controlling for age, sex, lifestyle, vascular risk factors, chronic kidney disease, cancer, serum c‐reactive protein, and APOE genotype. Result Of the 2244 participants, 5% had only anemia and 17% had only CVD. Both anemia and CVD were independently associated with a steeper decline in global cognitive composite score (anemia ‐0.01/year; 95%CI ‐0.03 to ‐0.00, CVD ‐0.02/year; 95%CI ‐0.03 to ‐0.02). Anemia was associated with faster decline in category fluency and perceptual speed, while CVD was significantly associated with an accelerated decline in all examined cognitive domains. Both anemia and CVD at baseline were associated with a steeper decline in total brain tissue volume, while CVD was additionally associated with steeper decline in volumes of hippocampus (P<0.05). Neither was significantly associated with changes in cSVD markers (i.e., white‐matter hyperintensities, lacunes). Conclusion Both anemia and CVD are risk factors for accelerated cognitive decline and brain atrophy in older adults.