The joint effect of apolipoprotein E ε4 and MRI findings on lower- extremity function and decline in cognitive function

Dorit Carmelli, Charles DeCarli, Gary E. Swan, Maggie Kelly-Hayes, Philip A. Wolf, Terry Reed, Jack M. Guralnik

Research output: Contribution to journalArticlepeer-review

59 Scopus citations


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 ε4 (ApoE-ε4) allele. The objective of this study was to investigate the joint effect of ApoE-ε4 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-ε4 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-ε4 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-ε4.

Original languageEnglish (US)
JournalJournals of Gerontology - Series A Biological Sciences and Medical Sciences
Issue number2
StatePublished - Feb 2000
Externally publishedYes

ASJC Scopus subject areas

  • Aging


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