Regional Gray Matter Volumes as Related to Psychomotor Slowing in Adults with Type 1 Diabetes

Abstract

OBJECTIVE Psychomotor slowing is a common cognitive complication in type 1 diabetes (T1D), but its neuroanatomical correlates and risk factors are unclear. In non-diabetic adults, smaller gray matter volume (GMV) and presence of white matter hyperintensities (WMH) are associated with psychomotor slowing. We hypothesize that smaller GMV in prefronto-parietal regions explains T1D-related psychomotor slowing. We also inspect the contribution of microvascular disease and hyperglycemia. METHODS GMV, WMH, and glucose levels were measured concurrently with a test of psychomotor speed (Digit Symbol Substitution Test, DSST) in 95 adults with childhood-onset T1D (mean age/duration=49/41 years) and 135 similarly-aged non-T1D adults. Linear regression models tested associations between DSST and regional GMV, controlling for T1D, sex, and education; a bootstrapping method tested whether regional GMV explained between-group differences in DSST. For the T1D cohort, voxel-based and a priori regions-of-interest methods further tested associations between GMV and DSST, adjusting for WMH, hyperglycemia, and age. RESULTS Bilateral putamen, but not other regions, significantly attenuated DSST differences between the cohorts (bootstrapped unstandardized indirect effects: −3.49, −3.26; 95% confidence limits [−5.49, −1.80], [−5.29 −1.44], left and right putamen, respectively). Among T1D, DSST was positively associated with GMV of bilateral putamen and left thalamus. Neither WMH, hyperglycemia, age, nor other factors substantially modified these relationships. CONCLUSIONS For middle-aged adults with T1D and cerebral microvascular disease, GMV of basal ganglia may play a critical role in regulating psychomotor speed, as measured via DSST. Studies to quantify the impact of basal ganglia atrophy concurrent with WMH progression on psychomotor slowing are warranted.

Basal ganglia cerebral blood flow associates with psychomotor speed in adults with type 1 diabetes

“…The functional connectivity of the basal ganglia is altered in response to hypoglycemia in individuals with T1DM (Bolo et al 2015b), and changes in basal ganglia volume have been documented in a pediatric sample of individuals with T1DM(Northam et al 2009). These data build upon findings in the basal ganglia by our group (Hughes et al 2013; Hwang et al 2016; Nunley et al 2017) and others (Bolo et al 2015a; Cranston et al 2001; Gallardo-Moreno et al 2015; Heikkilä et al 2010; Moulton et al 2015; Pell et al 2012; Rooijackers et al 2016; Seaquist 2015; Selvarajah et al 2011).…”

“…In non diabetic populations, the basal ganglia are especially vulnerable to SVD due to their poor collateral vascularization (watershed areas) (Pantoni 2010). The basal ganglia appear especially vulnerable to T1D, as shown by our group (Hughes et al 2013; Hwang et al 2016; Nunley et al 2017) and others (Bolo et al 2015a; Cranston et al 2001; Gallardo-Moreno et al 2015; Heikkilä et al 2010; Moulton et al 2015; Pell et al 2012; Rooijackers et al 2016; Seaquist 2015; Selvarajah et al 2011). Abnormalities in the basal ganglia is of concern in T1D, because of their role in hypoglycemia unawareness(Bolo et al 2015a; Cranston et al 2001; Heikkilä et al 2010; Rooijackers et al 2016), as well as in decision making(Mogenson et al 1980), thus potentially affecting diabetes management.…”

Cognitive Function Deficits Associated With Long-Duration Type 1 Diabetes and Vascular Complications

“…We found that psychomotor speed was slower in both older individuals with type1 and older individuals with type 2 diabetes compared with control subjects. Psychomotor speed is typically impaired in type 1 diabetes and may be tied to basal ganglia or white matter integrity (30). In our earlier research using voxel-based morphometry, we showed hyperglycemiaassociated reduced gray matter density in posterior cingulate, superior temporal gyrus, and parahippocampal gyri (23).…”

Altered Gray Matter Volume in Patients With Type 1 Diabetes Mellitus

“…Many previous studies have reported gray matter volume alterations in many different brain regions in patients with T1DM, which includes the superior frontal gyrus, middle frontal gyrus, middle temporal gyrus, thalamus and cerebellum (5)(6)(7)(8)(9). These changes are thought have some relations with the cognitive impairment in patients with T1DM.…”