PT - JOURNAL ARTICLE AU - Rui Wang AU - Laura Fratiglioni AU - Erika J. Laukka AU - Martin Lövdén AU - Grégoria Kalpouzos AU - Lina Keller AU - Caroline Graff AU - Alireza Salami AU - Lars Bäckman AU - Chengxuan Qiu TI - Effects of vascular risk factors and <em>APOE</em> ε4 on white matter integrity and cognitive decline AID - 10.1212/WNL.0000000000001379 DP - 2015 Mar 17 TA - Neurology PG - 1128--1135 VI - 84 IP - 11 4099 - http://n.neurology.org/content/84/11/1128.short 4100 - http://n.neurology.org/content/84/11/1128.full SO - Neurology2015 Mar 17; 84 AB - Objective: To investigate the effects of vascular risk factors and APOE status on white matter microstructure, and subsequent cognitive decline among older people.Methods: This study included 241 participants (age 60 years and older) from the population-based Swedish National Study on Aging and Care in Kungsholmen in central Stockholm, Sweden, who were free of dementia and stroke at baseline (2001–2004). We collected data through interviews, clinical examinations, and laboratory tests. We measured fractional anisotropy (FA) and mean diffusivity (MD) on diffusion tensor imaging, and estimated volume of white matter hyperintensities using automatic segmentation. We assessed global cognitive function with the Mini-Mental State Examination at baseline and at 3- and/or 6-year follow-up. We analyzed the data using multivariate linear regression and linear mixed models.Results: Heavy alcohol consumption, hypertension, and diabetes were significantly associated with lower FA or higher MD (p &lt; 0.05). When aggregating heavy alcohol consumption, hypertension, and diabetes together with current smoking, having an increasing number of these 4 factors concurrently was associated with decreasing FA and increasing MD (ptrend &lt; 0.01), independent of white matter hyperintensities. Vascular risk factors and APOE ε4 allele interacted to negatively affect white matter microstructure; having multiple (≥2) vascular factors was particularly detrimental to white matter integrity among APOE ε4 carriers. Lower tertile of FA and upper tertile of MD were significantly associated with faster Mini-Mental State Examination decline.Conclusions: Vascular risk factors are associated with reduced white matter integrity among older adults, which subsequently predicted faster cognitive decline. The detrimental effects of vascular risk factors on white matter microstructure were exacerbated among APOE ε4 carriers.DTI=diffusion tensor imaging; FA=fractional anisotropy; MD=mean diffusivity; MMSE=Mini-Mental State Examination; SNAC-K=Swedish National Study on Aging and Care in Kungsholmen; WMH=white matter hyperintensity