Genetic effects and age explain individual differences in brain structure in late middle age

According to a new study, genetic effects play important role in the brain white matter microstructure in late middle age. The same study found that greater age was associated with poorer white matter tract properties.

Previous studies have suggested that individual differences in the microstructure of white matter are largely explained by genetic effects. As most previous studies were conducted in children and young adults, there has been less knowledge about the importance of genetic and environmental influences on the white matter tracts later in life.

A recently published Finnish-American study indicates that individual differences in the white matter microstructure in late middle age are explained to a large extent by genetic effects. At the global level, genetic effects accounted for about 75% of the variance in the white matter microstructure.

It is known that there occurs decline in white matter in the old age, and to a greater extent in those with Alzheimer’s Disease (the most common cause of dementia). The new study found that age is associated with white matter decline already in late middle age, a transition period before the old age when dementias become more prevalent.

The study included 393 male twins (Vietnam Era Twin Study of Aging, VETSA), aged between 56 and 66 at the time of the study. “Age-related deterioration of white matter tracts was already apparent in these men,” states Eero Vuoksimaa, docent of neuropsychology at the University of Helsinki.

The study used diffusion tensor imaging (DTI) to map the white matter tracts. DTI, magnetic resonance imaging based method, makes it possible to measure the diffusion of water molecules in brain tissue. This enables to study white matter tracts in the brain. White matter tracts consist of axons and they transfer information from one brain region to another. The diffusion indices employed in the study reflect, e.g., the myelination of axons as well as demyelination and axonal damage.

The study mapped corpus callosum, a bundle of fibers connecting the two hemispheres of the brain, as well as 12 bilateral tracts connecting different brain regions within hemispheres. By studying both identical (monozygotic) and non-identical (dizygotic) twins, the researchers calculated heritability estimates which tell how much of the variance in white matter tracts is due to genetic influences.

The new study shows that the effects of ageing are apparent in the brain already in middle age, before memory disorders become more common. The DTI indices of fractional anisotropy (a measure of directional diffusivity) and absolute diffusivity (non-directional measures of mean, radial and axial diffusivities) used in this study may be more age-sensitive than traditional structural brain measures.

According to Vuoksimaa, future research could aim to determine which set of genes underlie the heritability of white matter tracts.

 “An ongoing follow-up data collection allows to investigate the changes from late middle age to early old age in white matter tracts – it will also be possible to determine whether the impact of genetic factors changes as we age and how such changes are associated with memory and other cognitive functions”

The VETSA study is funded by the National Institute on Aging (National Institutes of Health), USA, and Eero Vuoksimaa was supported by the Academy of Finland.

More information:

Eero Vuoksimaa, Adjunct Professor of Neuropsychology
Institute for Molecular Medicine Finland (FIMM), University of Helsinki
Tel. +358 2941 27586


Reference: Vuoksimaa E, Panizzon MS, Hagler DJ Jr, Hatton SN, Fennema-Notestine C, Rinker D, Eyler LT, Franz CE, Lyons MJ, Neale MC, Tsuang MT, Dale AM, Kremen WS. 2016 Dec 29. Heritability of white matter microstructure in late middle age: A twin study of tract-based fractional anisotropy and absolute diffusivity indices. Human Brain Mapping doi: 10.1002/hbm.23502.