title: Mixed brain lesions mediate the association between cardiovascular risk burden and cognitive decline in old age: A population-based study.
abstract: BACKGROUND
  The underlying pathological mechanisms linking cardiovascular burden to cognitive decline remain unclear.
  
  
  METHODS
  We investigated the associations of the Framingham general cardiovascular risk score (FGCRS), apolipoprotein E (APOE) ε4, and brain structure with the Mini-Mental State Examination (MMSE) decline using the 9-year follow-up data from Swedish National Study on Aging and Care in Kungsholmen (n = 2189, age ≥60) and the embedded magnetic resonance imaging (MRI) (n = 448) studies. Volumes of white matter hyperintensities (WMHs), total gray matter, ventricles, and hippocampus were assessed in the MRI sample.
  
  
  RESULTS
  A higher FGCRS was associated with faster MMSE decline in young-old people (60-72 years) but not in old-old (≥78 years). Larger volumes of cerebral WMHs and ventricles and smaller volumes of total gray matter and hippocampus were all associated with accelerated MMSE decline (P < .01); these associations were stronger among APOE ε4 carriers than noncarriers. Simultaneously entering multiple brain lesion markers as mediators in the model substantially attenuated the association between FGCRS and MMSE decline.
  
  
  CONCLUSIONS
  The effect of cardiovascular risk burden on cognitive deterioration in old age is largely mediated by mixed brain lesions.
authors: Aging Research Center, Department of Neurobiology, Care Sciences and Society (NVS), Karolinska Institutet-Stockholm University, Stockholm, Sweden. Electronic address: rui.wang@ki.se.
authors: Rui
authors: R
authors: Wang
authors: Aging Research Center, Department of Neurobiology, Care Sciences and Society (NVS), Karolinska Institutet-Stockholm University, Stockholm, Sweden; Stockholm Gerontology Research Center, Stockholm, Sweden.
authors: Laura
authors: L
authors: Fratiglioni
authors: Aging Research Center, Department of Neurobiology, Care Sciences and Society (NVS), Karolinska Institutet-Stockholm University, Stockholm, Sweden.
authors: Grégoria
authors: G
authors: Kalpouzos
authors: Aging Research Center, Department of Neurobiology, Care Sciences and Society (NVS), Karolinska Institutet-Stockholm University, Stockholm, Sweden.
authors: Martin
authors: M
authors: Lövdén
authors: Aging Research Center, Department of Neurobiology, Care Sciences and Society (NVS), Karolinska Institutet-Stockholm University, Stockholm, Sweden.
authors: Erika J
authors: EJ
authors: Laukka
authors: Division of Medical Imaging and Technology, Department of Clinical Science, Intervention and Technology, Karolinska Institutet, Stockholm, Sweden.
authors: Lena
authors: L
authors: Bronge
authors: Division of Clinical Geriatrics, Department of NVS, Karolinska University Hospital at Huddinge, Stockholm, Sweden.
authors: Lars-Olof
authors: LO
authors: Wahlund
authors: Aging Research Center, Department of Neurobiology, Care Sciences and Society (NVS), Karolinska Institutet-Stockholm University, Stockholm, Sweden; Stockholm Gerontology Research Center, Stockholm, Sweden.
authors: Lars
authors: L
authors: Bäckman
authors: Aging Research Center, Department of Neurobiology, Care Sciences and Society (NVS), Karolinska Institutet-Stockholm University, Stockholm, Sweden. Electronic address: chengxuan.qiu@ki.se.
authors: Chengxuan
authors: C
authors: Qiu
mesh_terms: D000367:Age Factors; D000368:Aged; D000369:Aged, 80 and over; D001057:Apolipoproteins E / Q000235:genetics; D001921:Brain / Q000000981:diagnostic imaging / Q000473:pathology*; D002318:Cardiovascular Diseases / Q000000981:diagnostic imaging / Q000453:epidemiology* / Q000235:genetics / Q000473:pathology*; D060825:Cognitive Dysfunction / Q000000981:diagnostic imaging / Q000453:epidemiology* / Q000235:genetics; D018672:Community Health Planning; D005260:Female; D006801:Humans; D008137:Longitudinal Studies; D008279:Magnetic Resonance Imaging; D008297:Male; D008609:Mental Status Schedule; D008875:Middle Aged; D009483:Neuropsychological Tests; D018709:Statistics, Nonparametric
chemical_list: D001057:Apolipoproteins E
keywords: Aging; Cerebral small-vessel disease; Cognitive decline; Framingham general cardiovascular risk score; Magnetic resonance imaging; Population study