Premature Aging in Autism: The Double Jeopardy Hypothesis of White Matter Integrity

Background:  Typical development of brain white matter (WM) microstructure across the lifespan shows a curvilinear pattern with a plateau around mid-adulthood and a rapid decrease in old age. Autism spectrum disorder (ASD) is typified as a brain connectivity disorder in which WM abnormalities are already present early on in life. However, it is unknown whether older adults with ASD show similar age-related WM deterioration as observed in typical aging.

Objectives: The aim of this first cross-sectional study in mid and late adulthood in ASD was to characterize WM integrity and its relationship with age.

Methods:  We utilized diffusion tensor imaging with head motion control in 48 adults with ASD and 48 age-matched controls (30-75 years, IQ>80), who completed a Flanker task. We focused on fractional anisotropy, and mean, axial, and radial diffusivity of 18 major fiber tracts. Intra-individual variability (IIV) measures based on performance on the Flanker interference task were used to assess IIV-WM integrity associations between groups.

Results:  We observed widespread reductions in white matter integrity in ASD, which persisted after taking head motion into account. These alterations were generally found in long-range association and projection tracts. Importantly, group-by-age interactions revealed increased age-related white matter deterioration in ASD, again for major association and projection fibers in the brain. We also observed different IIV-white matter integrity relations between groups. For example, reduced fiber coherence in callosal fibers was associated with higher IIV (when controlling for differences in MRT) in ASD, but not in controls.

Conclusions:  The observed white matter integrity reductions lend support to the structural under connectivity hypothesis in ASD. These reductions seem to have behavioral repercussions given an atypical relationship with IIV. Taken together, the current results may suggest a premature aging pattern in adults with ASD.