title: Effects of vascular risk factors and APOE ε4 on white matter integrity and cognitive decline.
abstract: 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 < 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 < 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.
authors: From the Aging Research Center (R.W., L.F., E.J.L., M.L., G.K., L.K., A.S., L.B., C.Q.), Department of Neurobiology, Care Sciences and Society, Karolinska Institutet-Stockholm University; Stockholm Gerontology Research Center (L.F., L.B.); and Division of Neurogeriatrics (C.G.), Department of Neurobiology, Care Sciences and Society, Karolinska Institutet, Center for Alzheimer Research at Karolinska Institutet, Sweden. rui.wang@ki.se chengxuan.qiu@ki.se.
authors: Rui
authors: R
authors: Wang
authors: From the Aging Research Center (R.W., L.F., E.J.L., M.L., G.K., L.K., A.S., L.B., C.Q.), Department of Neurobiology, Care Sciences and Society, Karolinska Institutet-Stockholm University; Stockholm Gerontology Research Center (L.F., L.B.); and Division of Neurogeriatrics (C.G.), Department of Neurobiology, Care Sciences and Society, Karolinska Institutet, Center for Alzheimer Research at Karolinska Institutet, Sweden.
authors: Laura
authors: L
authors: Fratiglioni
authors: From the Aging Research Center (R.W., L.F., E.J.L., M.L., G.K., L.K., A.S., L.B., C.Q.), Department of Neurobiology, Care Sciences and Society, Karolinska Institutet-Stockholm University; Stockholm Gerontology Research Center (L.F., L.B.); and Division of Neurogeriatrics (C.G.), Department of Neurobiology, Care Sciences and Society, Karolinska Institutet, Center for Alzheimer Research at Karolinska Institutet, Sweden.
authors: Erika J
authors: EJ
authors: Laukka
authors: From the Aging Research Center (R.W., L.F., E.J.L., M.L., G.K., L.K., A.S., L.B., C.Q.), Department of Neurobiology, Care Sciences and Society, Karolinska Institutet-Stockholm University; Stockholm Gerontology Research Center (L.F., L.B.); and Division of Neurogeriatrics (C.G.), Department of Neurobiology, Care Sciences and Society, Karolinska Institutet, Center for Alzheimer Research at Karolinska Institutet, Sweden.
authors: Martin
authors: M
authors: Lövdén
authors: From the Aging Research Center (R.W., L.F., E.J.L., M.L., G.K., L.K., A.S., L.B., C.Q.), Department of Neurobiology, Care Sciences and Society, Karolinska Institutet-Stockholm University; Stockholm Gerontology Research Center (L.F., L.B.); and Division of Neurogeriatrics (C.G.), Department of Neurobiology, Care Sciences and Society, Karolinska Institutet, Center for Alzheimer Research at Karolinska Institutet, Sweden.
authors: Grégoria
authors: G
authors: Kalpouzos
authors: From the Aging Research Center (R.W., L.F., E.J.L., M.L., G.K., L.K., A.S., L.B., C.Q.), Department of Neurobiology, Care Sciences and Society, Karolinska Institutet-Stockholm University; Stockholm Gerontology Research Center (L.F., L.B.); and Division of Neurogeriatrics (C.G.), Department of Neurobiology, Care Sciences and Society, Karolinska Institutet, Center for Alzheimer Research at Karolinska Institutet, Sweden.
authors: Lina
authors: L
authors: Keller
authors: From the Aging Research Center (R.W., L.F., E.J.L., M.L., G.K., L.K., A.S., L.B., C.Q.), Department of Neurobiology, Care Sciences and Society, Karolinska Institutet-Stockholm University; Stockholm Gerontology Research Center (L.F., L.B.); and Division of Neurogeriatrics (C.G.), Department of Neurobiology, Care Sciences and Society, Karolinska Institutet, Center for Alzheimer Research at Karolinska Institutet, Sweden.
authors: Caroline
authors: C
authors: Graff
authors: From the Aging Research Center (R.W., L.F., E.J.L., M.L., G.K., L.K., A.S., L.B., C.Q.), Department of Neurobiology, Care Sciences and Society, Karolinska Institutet-Stockholm University; Stockholm Gerontology Research Center (L.F., L.B.); and Division of Neurogeriatrics (C.G.), Department of Neurobiology, Care Sciences and Society, Karolinska Institutet, Center for Alzheimer Research at Karolinska Institutet, Sweden.
authors: Alireza
authors: A
authors: Salami
authors: From the Aging Research Center (R.W., L.F., E.J.L., M.L., G.K., L.K., A.S., L.B., C.Q.), Department of Neurobiology, Care Sciences and Society, Karolinska Institutet-Stockholm University; Stockholm Gerontology Research Center (L.F., L.B.); and Division of Neurogeriatrics (C.G.), Department of Neurobiology, Care Sciences and Society, Karolinska Institutet, Center for Alzheimer Research at Karolinska Institutet, Sweden.
authors: Lars
authors: L
authors: Bäckman
authors: From the Aging Research Center (R.W., L.F., E.J.L., M.L., G.K., L.K., A.S., L.B., C.Q.), Department of Neurobiology, Care Sciences and Society, Karolinska Institutet-Stockholm University; Stockholm Gerontology Research Center (L.F., L.B.); and Division of Neurogeriatrics (C.G.), Department of Neurobiology, Care Sciences and Society, Karolinska Institutet, Center for Alzheimer Research at Karolinska Institutet, Sweden. rui.wang@ki.se chengxuan.qiu@ki.se.
authors: Chengxuan
authors: C
authors: Qiu
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D053327:Apolipoprotein E4 / Q000235:genetics*; D003072:Cognition Disorders / Q000175:diagnosis / Q000453:epidemiology* / Q000235:genetics*; D056324:Diffusion Tensor Imaging / Q000639:trends; D005260:Female; D006579:Heterozygote; D006801:Humans; D008297:Male; D008875:Middle Aged; D011159:Population Surveillance / Q000379:methods; D012307:Risk Factors; D013548:Sweden / Q000453:epidemiology; D014652:Vascular Diseases / Q000175:diagnosis / Q000453:epidemiology* / Q000235:genetics*; D066127:White Matter / Q000473:pathology*
chemical_list: D053327:Apolipoprotein E4