title: The joint effect of apolipoprotein E epsilon4 and MRI findings on lower-extremity function and decline in cognitive function.
abstract: BACKGROUND
  Cognitive decline and poor physical function are risk factors for disability in old age and may occur more often in subjects with the apolipoprotein E epsilon4 (ApoE-epsilon4) allele. The objective of this study was to investigate the joint effect of ApoE-epsilon4 and structural changes detected on MRI brain scans on cognitive decline and lower-extremity function.
  
  
  METHODS
  Brain MRI (1.5 T), neuropsychological tests, and lower-extremity physical function tests were administered to World War II male veteran twins ages 69 to 80. Quantification of MRI scans used a previously published algorithm to segment brain images into total cerebral brain (TCB), cerebrospinal fluid (CSF), and white-matter hyperintensity (WMH) volumes. A short battery of physical performance tests was used to assess lower-extremity function. Ten-year changes in performance on the Mini-Mental State Exam (MMSE), the Benton Visual Retention Test (BVRT), and the Digit Symbol Substitution (DSS) test were used to assess cognitive decline.
  
  
  RESULTS
  For the sample as a whole, the comparison of subjects by median split of total cerebral brain volume found that those with brain volumes below the median performed worse on tests of gait and balance (p < .01) and experienced greater cognitive decline on the MMSE and BVRT cognitive test batteries (both p < .01). In addition, subjects with WMH volumes above the median had poor performance on the standing balance tasks and experienced greater decline on the DSS test (p < .01). Stratified analyses revealed that the joint effect of radiological findings and the ApoE-epsilon4 allele on cognitive decline and lower-extremity function was often greater than that expected from the separate effects combined.
  
  
  CONCLUSIONS
  We conclude that radiological findings in conjunction with ApoE-epsilon4 may single out a group at higher risk for dementia. We speculate that the observed interaction effect may be due to increased susceptibility to brain injury or impaired repair mechanisms in subjects with ApoE-epsilon4.
authors.affiliation: Center for Health Sciences, SRI International, Menlo Park, California 94025, USA. doritc@unix.sri.com
authors.forename: D
authors.initials: D
authors.lastname: Carmelli
authors.forename: C
authors.initials: C
authors.lastname: DeCarli
authors.forename: G E
authors.initials: GE
authors.lastname: Swan
authors.forename: M
authors.initials: M
authors.lastname: Kelly-Hayes
authors.forename: P A
authors.initials: PA
authors.lastname: Wolf
authors.forename: T
authors.initials: T
authors.lastname: Reed
authors.forename: J M
authors.initials: JM
authors.lastname: Guralnik
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000465:Algorithms; D000483:Alleles; D053327:Apolipoprotein E4; D001057:Apolipoproteins E / Q000235:genetics*; D001921:Brain / Q000473:pathology*; D002555:Cerebrospinal Fluid; D003071:Cognition / Q000502:physiology; D003072:Cognition Disorders / Q000503:physiopathology*; D015331:Cohort Studies; D003627:Data Interpretation, Statistical; D006233:Persons with Disabilities; D005500:Follow-Up Studies; D005684:Gait / Q000502:physiology; D006801:Humans; D007866:Leg / Q000502:physiology*; D008137:Longitudinal Studies; D008279:Magnetic Resonance Imaging; D008297:Male; D008568:Memory / Q000502:physiology; D009483:Neuropsychological Tests; D004856:Postural Balance / Q000502:physiology; D011597:Psychomotor Performance / Q000502:physiology*; D012307:Risk Factors
chemical_list: D053327:Apolipoprotein E4; D001057:Apolipoproteins E