Discussion
cognitive impairment, gray matter atrophy, T1D, atrophy, SPARE-AD atrophy, AD-related neurodegeneration, diabetes
BRAIN ATROPHY, BRAIN, ATROPHY, COMPLICATIONS, DIABETES
In this cohort study, we used novel machine learning methods to identify spatial patterns of brain atrophy and found that T1D was associated with an increase in brain age relative to individuals without diabetes. TID was not associated with a pattern consistent with early AD-related neurodegeneration. Our data suggest that, on average, individuals with T1D have brain atrophy patterns that were equivalent to approximately 6 years older age compared with the participants' chronological age, while controls without T1D showed no evidence of premature brain aging. These results support the hypothesis that brain morphology is associated with an accelerating aging process in middle-aged and older-aged adults with a long history of T1D.Our study suggested that T1D was associated with pronounced gray matter atrophy in the putamen, thalamus, superior frontal gyrus, middle frontal gyrus, and superior temporal gyrus. These regions are known to provide important information for the SPARE-BA measure (We did not assay for amyloid and tau biomarkers in the EDIC study to directly evaluate the prevalence of AD neuropathologic change. However, the EDIC participants with T1D and control participants without diabetes had comparable measures of atrophy in AD-signature regions, with both showing mean SPARE-AD values in the range of normal controls. This suggests that T1D is not associated with significantly decreased brain reserve in regions that are susceptible to AD-related neurodegeneration at this age. Risk factors, spanning demographic measures to vascular risk factors to diabetes-related complications, did not show significant associations with SPARE-AD or SPARE-BA measures, failing to identify a potential direct mechanism for the effects of T1D on brain health.Previously in the iSTAGING sample, we found that advanced brain aging patterns in controls without T1D were associated with lower executive function but not worse memory performance. In contrast, higher SPARE-AD, characterized by a pattern showing greater atrophy in temporal lobe regions, was associated with both executive function and memory. In EDIC participants, SPARE-AD atrophy patterns seem to be associated with psychomotor and mental efficiency as well as memory. Brain aging was only associated with worse psychomotor and mental efficiency. These findings support the hypothesis that different regional atrophy patterns are associated with different cognitive impairment profiles.