title: Do cardiovascular risk factors explain the link between white matter hyperintensities and brain volumes in old age? A population-based study.
abstract: OBJECTIVE
  White matter hyperintensities (WMHs) and brain atrophy frequently coexist in older people. However, it is unclear whether the association between these two brain lesions is dependent on the aging process, a vascular mechanism or genetic susceptibility. It was therefore investigated whether the association between load of WMHs and brain atrophy measures is related to age, vascular risk factors (VRFs) or the APOE-ε4 allele.
  
  
  METHODS
  This population-based study included 492 participants (age ≥60 years, 59.6% women) free of dementia and stroke. Data on demographics, VRFs and APOE genotypes were collected through interviews, clinical examination and laboratory tests. WMHs on magnetic resonance images were assessed using manual visual rating and automatic volumetric segmentation. Hippocampal and ventricular volumes were manually delineated, whereas total gray matter (GM) volume was measured by automatic segmentation. Data were analyzed with multivariate linear regression models.
  
  
  RESULTS
  More global WMHs, assessed using either a visual rating scale or a volumetric approach, were significantly associated with lower GM volume and higher ventricular volume; the associations remained significant after adjusting for age, VRFs and the APOE-ε4 allele. In contrast, the association between global WMHs and hippocampal volume was no longer significant after adjusting for age, whereas adjustment for VRFs and APOE-ε4 had no influential effect.
  
  
  CONCLUSIONS
  The association of global WMHs with lower GM volume and higher ventricular volume is independent of age, VRFs and APOE-ε4 allele, suggesting that the process of cerebral microvascular disease and neurodegeneration are associated independently of the normal aging process, vascular mechanisms or genetic susceptibility.
authors: Aging Research Center, Department of Neurobiology, Care Sciences and Society (NVS), Karolinska Institutet (KI) - Stockholm University, Stockholm, Sweden.
authors: R
authors: R
authors: Wang
authors: Aging Research Center, Department of Neurobiology, Care Sciences and Society (NVS), Karolinska Institutet (KI) - Stockholm University, Stockholm, Sweden.|Stockholm Gerontology Research Center, Stockholm, Sweden.
authors: L
authors: L
authors: Fratiglioni
authors: Division of Medical Imaging and Technology, Department of Clinical Science, Intervention and Technology, KI, Stockholm, Sweden.
authors: A
authors: A
authors: Laveskog
authors: Aging Research Center, Department of Neurobiology, Care Sciences and Society (NVS), Karolinska Institutet (KI) - Stockholm University, Stockholm, Sweden.
authors: G
authors: G
authors: Kalpouzos
authors: Aging Research Center, Department of Neurobiology, Care Sciences and Society (NVS), Karolinska Institutet (KI) - Stockholm University, Stockholm, Sweden.
authors: C-H
authors: CH
authors: Ehrenkrona
authors: Department of Diagnostic Radiology, Radiation Sciences, Umeå University, Umeå, Sweden.
authors: Y
authors: Y
authors: Zhang
authors: Division of Medical Imaging and Technology, Department of Clinical Science, Intervention and Technology, KI, Stockholm, Sweden.
authors: L
authors: L
authors: Bronge
authors: Division of Clinical Geriatrics, NVS, Karolinska University Hospital at Huddinge, Stockholm, Sweden.
authors: L-O
authors: LO
authors: Wahlund
authors: Aging Research Center, Department of Neurobiology, Care Sciences and Society (NVS), Karolinska Institutet (KI) - Stockholm University, Stockholm, Sweden.|Stockholm Gerontology Research Center, Stockholm, Sweden.
authors: L
authors: L
authors: Bäckman
authors: Aging Research Center, Department of Neurobiology, Care Sciences and Society (NVS), Karolinska Institutet (KI) - Stockholm University, Stockholm, Sweden.
authors: C
authors: C
authors: Qiu
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000375:Aging / Q000473:pathology*; D001057:Apolipoproteins E / Q000235:genetics*; D001284:Atrophy / Q000473:pathology; D002318:Cardiovascular Diseases / Q000453:epidemiology*; D002552:Cerebral Ventricles / Q000473:pathology*; D005260:Female; D005838:Genotype; D066128:Gray Matter / Q000473:pathology*; D006624:Hippocampus / Q000473:pathology*; D006801:Humans; D056784:Leukoencephalopathies / Q000453:epidemiology / Q000473:pathology*; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D012307:Risk Factors; D013548:Sweden / Q000453:epidemiology; D066127:White Matter / Q000473:pathology*
chemical_list: D001057:Apolipoproteins E
keywords: APOE genotype; aging; brain volume; hippocampal volume; population-based study; vascular risk factors; white matter hyperintensities