Reduced Regional Cerebral Blood Flow Relates to Poorer Cognition in Older Adults With Type 2 Diabetes

Abstract

Type 2 diabetes mellitus (T2DM) increases risk for dementia, including Alzheimer’s disease (AD). Many previous studies of brain changes underlying cognitive impairment in T2DM have applied conventional structural magnetic resonance imaging (MRI) to detect macrostructural changes associated with cerebrovascular disease such as white matter hyperintensities or infarcts. However, such pathology likely reflects end-stage manifestations of chronic decrements in cerebral blood flow (CBF). MRI techniques that measure CBF may (1) elucidate mechanisms that precede irreversible parenchymal damage and (2) serve as a marker of risk for cognitive decline. CBF measured with arterial spin labeling (ASL) MRI may be a useful marker of perfusion deficits in T2DM and related conditions. We examined associations among T2DM, CBF, and cognition in a sample of 49 well-characterized nondemented older adults. Along with a standard T1-weighted scan, a pseudocontinuous ASL sequence optimized for older adults (by increasing post-labeling delays to allow more time for the blood to reach brain tissue) was obtained on a 3T GE scanner to measure regional CBF in FreeSurfer derived regions of interest. Participants also completed a neuropsychological assessment. Results showed no significant differences between individuals with and without T2DM in terms of cortical thickness or regional brain volume. However, adjusting for age, sex, comorbid vascular risk factors, and reference CBF (postcentral gyrus) older adults with T2DM demonstrated reduced CBF in the hippocampus, and inferior temporal, inferior parietal, and frontal cortices. Lower CBF was associated with poorer memory and executive function/processing speed. When adjusting for diabetes, the significant associations between lower regional CBF and poorer executive function/processing speed remained. Results demonstrate that CBF is reduced in older adults with T2DM, and suggest that CBF alterations likely precede volumetric changes. Notably, relative to nondiabetic control participants, those with T2DM showed lower CBF in predilection sites for AD pathology (medial temporal lobe and inferior parietal regions). Findings augment recent research suggesting that perfusion deficits may underlie cognitive decrements frequently observed among older adults with T2DM. Results also suggest that CBF measured with ASL MRI may reflect an early and important marker of risk of cognitive impairment in T2DM and related conditions.

Cognitive Performance Profile in Pediatric Moyamoya Disease Patients and Its Relationship With Regional Cerebral Blood Perfusion

“…Anatomical location of advanced cognitive function has undergone intensive investigation. Despite a few studies reporting a correlation between hemodynamic compromise in temporal lobe and cognitive impairment (26,30), more researchers found that regions in the frontal lobe are linked to executive function, both from aspects of hemodynamics and metabolism (4,15,31,32). Using multivariate linear regression to adjust for confounders, we found that the average CBF of the left temporal lobe independently associated with processing speed.…”

“…Researchers have discussed potential indicators of cognitive impairments of pediatric MMD patients. Longer duration of symptoms, cerebral infarction, and bilateral involvement had been suggested to associate with poorer cognitive performance (21,(24)(25)(26). However, these associations were not significant in a meta-analysis study (3).…”

Susceptibility to capillary plugging can predict brain region specific vessel loss with aging

“…CBF also appears to decline in a region-specific manner (Hagstadius and Risberg, 1989;Leenders et al, 1990;Martin et al, 1991;Chen et al, 2011 (Chen et al, 2011). There could be functional implications of this regional heterogeneity in CBF decline given that many imaging studies in humans have shown that higher CBF correlates with increased performance on tasks measuring executive functioning, attention, and memory in healthy subjects (Leeuwis et al, 2018), patients with vascular disease (such as type 2 diabetes) (Bangen et al, 2018), and patients with dementia (Nielsen et al, 2017).…”

Brain Metabolism Alterations in Type 2 Diabetes: What Did We Learn From Diet-Induced Diabetes Models?

“…Proteomic analyses suggest impaired metabolic activity in microvessels from the cerebral cortex of HFD-exposed mice compared to controls (Ouyang et al, 2014), even though HDF exposure results in limited increases of blood glucose levels (Soares et al, 2018;Lizarbe et al, 2019b). Such alterations are likely to impact brain perfusion and to limit nutrient delivery for fueling neuronal energetics (Glaser et al, 2012;Bangen et al, 2018). In mice, exposure to HFD impairs vascular reactivity (relaxation and contractile responses) and cerebral blood flow of the middle cerebral artery and of intraparenchymal micro vessels in prefrontal cortex and hippocampus, without changes of baseline perfusion (Pétrault et al, 2019).…”