A systematic review of type 2 diabetes mellitus and hypertension in imaging studies of cognitive aging: time to establish new norms

Abstract

The rising prevalence of type 2 diabetes (T2DM) and hypertension in older adults, and the deleterious effect of these conditions on cerebrovascular and brain health, is creating a growing discrepancy between the “typical” cognitive aging trajectory and a “healthy” cognitive aging trajectory. These changing health demographics make T2DM and hypertension important topics of study in their own right, and warrant attention from the perspective of cognitive aging neuroimaging research. Specifically, interpretation of individual or group differences in blood oxygenation level dependent magnetic resonance imaging (BOLD MRI) or positron emission tomography (PET H2O15) signals as reflective of differences in neural activation underlying a cognitive operation of interest requires assumptions of intact vascular health amongst the study participants. Without adequate screening, inclusion of individuals with T2DM or hypertension in “healthy” samples may introduce unwanted variability and bias to brain and/or cognitive measures, and increase potential for error. We conducted a systematic review of the cognitive aging neuroimaging literature to document the extent to which researchers account for these conditions. Of the 232 studies selected for review, few explicitly excluded individuals with T2DM (9%) or hypertension (13%). A large portion had exclusion criteria that made it difficult to determine whether T2DM or hypertension were excluded (44 and 37%), and many did not mention any selection criteria related to T2DM or hypertension (34 and 22%). Of all the surveyed studies, only 29% acknowledged or addressed the potential influence of intersubject vascular variability on the measured BOLD or PET signals. To reinforce the notion that individuals with T2DM and hypertension should not be overlooked as a potential source of bias, we also provide an overview of metabolic and vascular changes associated with T2DM and hypertension, as they relate to cerebrovascular and brain health.

The Trouble Interpreting fMRI Studies in Populations with Cerebrovascular Risk: The Use of a Subject-Specific Hemodynamic Response Function in a Study of Age, Vascular Risk, and Memory

“…Nevertheless, many studies investigating aging, health, and disease continue to use fMRI to infer differential brain functioning despite possibly violating the link between the BOLD signal and neural activity. A review by Meusel et al (2014) reported that 59%-78% of aging studies did not have clear subject-selection criteria for two factors known to change cerebrovascular health (i.e., hypertension diagnosis or Type 2 diabetes), and only about 30% of studies acknowledged the influence of cerebrovascular health on their results. These numbers suggest many extant findings may include inflated false positives or false negatives (Veldsman, Cumming, & Brodtmann, 2015).…”

Regulation of insulin sensitivity, insulin production, and pancreatic β cell survival by angiotensin-(1-7) in a rat model of streptozotocin-induced diabetes mellitus

“…Diabetes mellitus (DM) is a chronic metabolic disorder characterized by elevated levels of blood glucose, which results from defects in insulin production, insulin action, or both [15]. Type 2 DM (also known as non-insulin-dependent diabetes) is the most common form of diabetes, affecting more than 300 million people worldwide [19].…”

Cerebrolysin reverses hippocampal neural atrophy in a mice model of diabetes mellitus type 1

“…Diabetes mellitus (DM) is a metabolic disorder that increases the risk of cognitive dysfunction and dementia (for reviews see Lee et al, ; Meusel et al, ). These disorders might be due in part to the occurrence of morphological changes at the cortical level (for review see Grillo and Reagan, ).…”