title: The association between cognitive function and white matter lesion location in older adults: a systematic review.
abstract: BACKGROUND
  Maintaining cognitive function is essential for healthy aging and to function autonomously within society. White matter lesions (WMLs) are associated with reduced cognitive function in older adults. However, whether their anatomical location moderates these associations is not well-established. This review systematically evaluates peer-reviewed evidence on the role of anatomical location in the association between WMLs and cognitive function.
  
  
  METHODS
  In accordance with the preferred reporting items for systematic reviews and meta-analysis (PRISMA) statement, databases of EMBASE, PUBMED, MEDLINE, and CINAHL, and reference lists of selected papers were searched. We limited our search results to adults aged 60 years and older, and studies published in the English language from 2000 to 2011. Studies that investigated the association between cognitive function and WML location were included. Two independent reviewers extracted: 1) study characteristics including sample size, sample characteristic, and study design; 2) WML outcomes including WML location, WML quantification method (scoring or volume measurement), strength of the MRI magnet in Tesla, and MRI sequence used for WML detection; and 3) cognitive function outcomes including cognitive tests for two cognitive domains of memory and executive function/processing speed.
  
  
  RESULTS
  Of the 14 studies included, seven compared the association of subcortical versus periventricular WMLs with cognitive function. Seven other studies investigated the association between WMLs in specific brain regions (e.g., frontal, parietal lobes) and cognitive function. Overall, the results show that a greater number of studies have found an association between periventricular WMLs and executive function/processing speed, than subcortical WMLs. However, whether WMLs in different brain regions have a differential effect on cognitive function remains unclear.
  
  
  CONCLUSIONS
  Evidence suggests that periventricular WMLs may have a significant negative impact on cognitive abilities of older adults. This finding may be influenced by study heterogeneity in: 1) MRI sequences, WML quantification methods, and neuropsychological batteries; 2) modifying effect of cardiovascular risk factors; and 3) quality of studies and lack of sample size calculation.
authors.affiliation: Department of Physical Therapy, University of British Columbia, 212-2177 Wesbrook Mall, Vancouver, BC V6T 1Z3, Canada.
authors.forename: Niousha
authors.initials: N
authors.lastname: Bolandzadeh
authors.forename: Jennifer C
authors.initials: JC
authors.lastname: Davis
authors.forename: Roger
authors.initials: R
authors.lastname: Tam
authors.forename: Todd C
authors.initials: TC
authors.lastname: Handy
authors.forename: Teresa
authors.initials: T
authors.lastname: Liu-Ambrose
mesh_terms: D000367:Age Factors; D000368:Aged; D001921:Brain / Q000473:pathology*; D003072:Cognition Disorders / Q000175:diagnosis* / Q000453:epidemiology*; D015897:Comorbidity; D056324:Diffusion Tensor Imaging / Q000706:statistics & numerical data*; D006801:Humans; D015994:Incidence; D056784:Leukoencephalopathies / Q000175:diagnosis* / Q000453:epidemiology*; D008875:Middle Aged; D009413:Nerve Fibers, Myelinated / Q000473:pathology*; D012307:Risk Factors