From the Center for Health Sciences, SRI International (formerly Stanford
Research Institute), Menlo Park, Calif (D.C., G.S., L.J.); the Department of
Neurology, Kansas University Medical Center, Kansas City, Kan (C.D.); the
Department of Medical Genetics, Indiana University School of Medicine,
Indianapolis, Ind (T.R.); the Department of Neurology, Boston University,
Boston, Mass (P.W.); and the Department of Neurology, Harbor-UCLA Medical
Center, Los Angeles, Calif (B.M.).
Correspondence to Dorit Carmelli, Center for Health Sciences, SRI International, 333 Ravenswood Ave, Menlo Park, CA 94025. E-mail dorit{at}gnomic.stanford.edu
Background and Purpose—White matter
hyperintensities (WMHs), as detected by MRI, are common among the
elderly and are frequently interpreted as representing a
subclinical form of ischemic brain damage. We used volumetric
MR techniques to investigate the contribution of genes and the
environment to measures of brain morphology in a sample of community
dwelling elderly male twins.
Methods—Brain MR (1.5 T) scans were obtained from 74 monozygotic
(MZ) and 71 dizygotic (DZ), white, male, World War II veteran twins
born in the United States and age 68 to 79 when scanned. MR
quantification used a previously published semiautomated segmentation
algorithm to segment brain images into total brain, cerebrospinal fluid
(CSF), and WMH volumes. Twin pair covariances were computed for
each measure, and structural equation genetic models were fitted to
these data.
Results—Total cranial, brain parenchyma, CSF, and WMH volumes
were highly correlated in MZ pairs, and correlations in MZ pairs were
significantly greater than those in DZ pairs. Structural equation
modeling indicated heritabilities of 91%, 92%, and 73%,
respectively, for total cranial, brain parenchyma, and WMH volumes.
Correction for age and head size reduced the heritability of brain
parenchyma to 62% (95% confidence interval, 56% to 68%) and the
heritability of WMH volume to 71% (95% confidence interval, 66% to
76%). Proband concordance rates for large amounts of WMH were 61% in
MZ pairs and 38% in DZ pairs, compared with a prevalence of 15% in
the entire sample.
Conclusions—This study is the first to quantify the relative
contribution of genetic and individual environmental influences to
measures of brain morphology in the elderly.
© 1998 American Heart Association, Inc.
Original Contributions
Evidence For Genetic Variance in White Matter Hyperintensity Volume in Normal Elderly Male Twins
Key Words: aging • genetics • magnetic resonance imaging • white matter
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