The joint effect of apolipoprotein E epsilon4 and MRI findings onlower- extremity function and decline in cognitive function

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Abstract
BACKGROUND: Cognitive decline and poor physical function are riskfactors for disability in old age and may occur more often in subjects withthe apolipoprotein E epsilon4 (ApoE-epsilon4) allele. The objective of thisstudy was to investigate the joint effect of ApoE- epsilon4 and structuralchanges detected on MRI brain scans on cognitive decline andlower-extremity function. METHODS: Brain MRI (1.5 T), neuropsychologicaltests, and lower-extremity physical function tests were administered toWorld War II male veteran twins ages 69 to 80. Quantification of MRI scansused a previously published algorithm to segment brain images into totalcerebral brain (TCB), cerebrospinal fluid (CSF), and white-matterhyperintensity (WMH) volumes. A short battery of physical performance testswas used to assess lower- extremity function. Ten-year changes inperformance on the Mini-Mental State Exam (MMSE), the Benton VisualRetention Test (BVRT), and the Digit Symbol Substitution (DSS) test wereused to assess cognitive decline. RESULTS: For the sample as a whole, thecomparison of subjects by median split of total cerebral brain volume foundthat those with brain volumes below the median performed worse on tests ofgait and balance (p < .01) and experienced greater cognitive decline onthe MMSE and BVRT cognitive test batteries (both p < .01). In addition,subjects with WMH volumes above the median had poor performance on thestanding balance tasks and experienced greater decline on the DSS test (p< .01). Stratified analyses revealed that the joint effect ofradiological findings and the ApoE-epsilon4 allele on cognitive decline andlower-extremity function was often greater than that expected from theseparate effects combined. CONCLUSIONS: We conclude that radiologicalfindings in conjunction with ApoE-epsilon4 may single out a group at higherrisk for dementia. We speculate that the observed interaction effect may bedue to increased susceptibility to brain injury or impaired repairmechanisms in subjects with ApoE-epsilon4.

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