Ventral Striatum, but Not Cortical Volume Loss, Is Related to Cognitive Dysfunction in Type 1 Diabetic Patients With and Without Microangiopathy

Abstract

OBJECTIVEPatients with longstanding type 1 diabetes may develop microangiopathy due to high cumulative glucose exposure. Also, chronic hyperglycemia is related to cerebral alterations and cognitive dysfunction. Whether the presence of microangiopathy is conditional to the development of hyperglycemia-related cerebral compromise is unclear. Since subcortical, rather than cortical, volume loss was previously related to cognitive dysfunction in other populations, we measured these brain correlates and cognitive functions in patients with longstanding type 1 diabetes with and without microangiopathy. RESEARCH DESIGN AND METHODSWe evaluated differences in subcortical volume and cortical thickness and volume in type 1 diabetic patients with (n = 51) and without (n = 53) proliferative retinopathy and 49 control subjects and related volume differences to cognitive dysfunction. Analyses were corrected for age, sex, systolic blood pressure, and A1C. RESULTSPutamen and right thalamic volume loss was noted in both patients with and without proliferative retinopathy compared with control subjects (all P < 0.05). Additionally, in patients with proliferative retinopathy relative to control subjects, volume loss of the bilateral nucleus accumbens was found (all P < 0.05). No differences were observed between the two patient groups. Cortical thickness and volume were not different between groups. In pooled analyses, lower left nucleus accumbens volume was associated with cognitive dysfunction (P < 0.035). CONCLUSIONSThis study shows subcortical, but not cortical, volume loss in relation to cognitive dysfunction in patients with longstanding type 1 diabetes, irrespective of microangiopathy. The time course, pathophysiology, and clinical relevance of these findings need to be established in longitudinal and mechanistic studies.Longstanding type 1 diabetes mellitus may lead to development of microangiopathy, mediated by cumulative hyperglycemic exposure (1). Cognitive dysfunction is also related to prolonged hyperglycemia (2,3). Proliferative retinopathy, the presence of which has been found to be independently related to cognition and cerebral alterations

Altered eigenvector centrality is related to local resting‐state network functional connectivity in patients with longstanding type 1 diabetes mellitus

“…In our study, we have previously shown that T1DM patients with proliferative retinopathy showed decrements in cognitive functions depending on processing speed and attention in comparison with controls and their counterparts with uncomplicated T1DM, and decreased processing speed in patients without proliferative retinopathy relative to controls [Van Duinkerken et al, ]. Although we did not demonstrate any alterations in cortical thickness, we did show lower subcortical gray matter volume in the thalamus, nucleus accumbens, putamen, and caudate nucleus [Van Duinkerken et al, ]. Both patients with and without proliferative retinopathy showed these alterations, albeit the effect size was largest in the group with retinopathy.…”

“…Based on the results of our previous RSN connectivity analysis, alterations were hypothesized strongest in patients without proliferative retinopathy. Next, in all patients, we aimed at identifying the relationship between potential alterations in ECM and degree centrality and previously observed cognitive decrements, altered RSN functional connectivity, and lower subcortical volume [Van Duinkerken et al, ]. To this end, we correlated ECM and degree centrality values with cognitive performance on the domains of general cognitive ability, information processing speed, and attention.…”

Putamen volume and its clinical and neurological correlates in primary HIV infection

“…The putamen (and the basal ganglia collectively) has been shown to be selectively injured in a number of diseases, with volume regional loss reported in Type 1 Diabetes [14], multiple sclerosis [15], and Alzheimer’s disease [16]. The mechanistic relationships between these conditions and HIV may be potentially related to inflammation or vascular injury, and warrant further investigation.…”

Diabetic retinopathy is a neurodegenerative disorder

“…61, 77-80 Many studies have established associations between diabetic cognitive dysfunction and progressive damage to brain structure, including increased cortical atrophy, microstructural abnormalities in white matter tracts, atrophy of the striatum (in type 1) and hippocampus (in type 2), and gray matter loss. 81-85 At the moment, it is not clear how diabetes causes these structural losses in the brain, given that the brain and its microvasculature are not easily accessible in vivo . 86, 87 The Diabetes Control and Complications Trial/Epidemiology of Diabetes Interventions and Complications (DCCT/EDIC) refuted the hypothesis that severe hypoglycemia caused cognitive dysfunction.…”

“…79 Several studies have shown an association between structural changes from diabetes in the brain and retinal microvasculopathy. 81, 88-91 Some authors therefore claim that the functional and structural changes in the brain induced by diabetes are primarily caused by microvasculopathy. 78, 88, 90, 92, 93 Other authors, however, claim that neuropathy results directly from hyperglycemia 86 or from frequent oscillations in serum glucose levels, 94 resulting in cognitive decline.…”