Association of Type 2 Diabetes Mellitus With Perivascular Spaces and Cerebral Amyloid Angiopathy in Alzheimer’s Disease: Insights From MRI Imaging

Munis, Özlem Bizpınar

doi:10.12779/dnd.2023.22.3.87

Cited by 9 publications

(4 citation statements)

References 30 publications

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“…T2DM is strongly associated with obesity-visceral adipose tissue (VAT), insulin resistance (IR), and MetS, which is known to have numerous, devastating complications including hypertension, vasculopathy (micro-macrovascular disease) with cerebrocardiovascular disease and stroke, peripheral neuropathy, retinopathy and blindness, neuropathy, non-traumatic amputation, and nephropathy. Importantly, T2DM is also associated with dilated EPVS and impaired glymphatic function of interstitial waste (including multiple neurotoxic substances that include misfolded amyloid beta and tau proteins) [25][26][27][28][29]. Additionally, peripheral and brain IR as well as MetS also play an important role in brain remodeling (Figure 9) [22,23,26,30,31].…”

Section: Obesity Metabolic Syndrome (Mets) Type 2 Diabetes Mellitus (...mentioning

confidence: 99%

“…Notably, T2DM is known to be associated with significant brain remodeling with cognitive impairment and dysfunction (CID), vascular cognitive impairment and dementia (VCID), and the development of EPVS [25,[27][28][29][30][31][32][33][34][35][36][37][38]. Interestingly, Fulop et al examined the brain's venous system and its role in the development of enlarged perivascular spaces [39].…”

Section: Obesity Metabolic Syndrome (Mets) Type 2 Diabetes Mellitus (...mentioning

confidence: 99%

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A Closer Look at the Perivascular Unit in the Development of Enlarged Perivascular Spaces in Obesity, Metabolic Syndrome, and Type 2 Diabetes Mellitus

Hayden

2024

Biomedicines

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The recently described perivascular unit (PVU) resides immediately adjacent to the true capillary neurovascular unit (NVU) in the postcapillary venule and contains the normal-benign perivascular spaces (PVS) and pathological enlarged perivascular spaces (EPVS). The PVS are important in that they have recently been identified to be the construct and the conduit responsible for the delivery of metabolic waste from the interstitial fluid to the ventricular cerebrospinal fluid for disposal into the systemic circulation, termed the glymphatic system. Importantly, the outermost boundary of the PVS is lined by protoplasmic perivascular astrocyte endfeet (pvACef) that communicate with regional neurons. As compared to the well-recognized and described neurovascular unit (NVU) and NVU coupling, the PVU is less well understood and remains an emerging concept. The primary focus of this narrative review is to compare the similarities and differences between these two units and discuss each of their structural and functional relationships and how they relate not only to brain homeostasis but also how they may relate to the development of multiple clinical neurological disease states and specifically how they may relate to obesity, metabolic syndrome, and type 2 diabetes mellitus. Additionally, the concept and importance of a perisynaptic astrocyte coupling to the neuronal synapses with pre- and postsynaptic neurons will also be considered as a perisynaptic unit to provide for the creation of the information transfer in the brain via synaptic transmission and brain homeostasis. Multiple electron microscopic images and illustrations will be utilized in order to help explain these complex units.

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Section: Obesity Metabolic Syndrome (Mets) Type 2 Diabetes Mellitus (...mentioning

confidence: 99%

Section: Obesity Metabolic Syndrome (Mets) Type 2 Diabetes Mellitus (...mentioning

confidence: 99%

A Closer Look at the Perivascular Unit in the Development of Enlarged Perivascular Spaces in Obesity, Metabolic Syndrome, and Type 2 Diabetes Mellitus

Hayden

2024

Biomedicines

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“…Importantly, T2DM is known to be associated with significant ultrastructure TEM brain remodeling with the development of SVD, cognitive impairment and dysfunction (CID), vascular cognitive impairment and dementia (VCID), MCI and depression with SVD including EPVS and CMBs. Notably, in the 20-week-old female obese, insulin resistance, metabolic syndrome, type 2 diabetes mellitus, preclinical diabetic db/db mouse models CMBs were found only in db/db mice and not control models or those db/db models treated with the antidiabetic medication empagliflozin [15, [75][76][77][78][79][80]82,83]. In the diabetic db/db models we were able to make multiple observations of BECact/dys including BEC abrupt thickening and loss of cytoplasm electron density, BEC Basement membrane thickening, with aberrant vacuole-like bodies, leukocyte, red blood cell, and platelet adherence to the activated BECs.…”

Section: Transmission Electron Microscopy (Tem) Imaging Of Brain Endo...mentioning

confidence: 99%

Cerebral Microbleeds Associate with Brain Endothelial Cell Activation-Dysfunction and Blood-Brain Barrier Dysfunction-Disruption with an Increased Risk of Hemorrhagic and Ischemic Stroke That Is Capable of Exacerbating Neurodegeneration

Hayden

2024

Preprint

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Cerebral microbleed(s) (CMBs) are increasingly being viewed not only as a marker for cerebral small vessel disease (SVD) but also as having an increased risk for the development of stroke (hemorrhagic/ischemic) and aging-related dementia. Recently, brain endothelial cell activation and dysfunction and blood-brain barrier dysfunction and/or disruption have been shown to be associated with SVD, enlarged perivascular spaces, and the development and evolution of CMBs. CMBs are a known disorder of cerebral microvessels that are visualized as 3-5mm, smooth, round or oval, and hypointense (black) lesions seen only on T2*-weighted gradient recall echo or susceptibility-weighted sequences on MRI images. CMBs (a global problem) are known to occur with high prevalence in community-dwelling older individuals. Since our current global population is the oldest recorded in history and only expected to continue to grow, we can only expect the health care burdens associated with CMBs to also grow. CMBs should raise a red flag regarding the increased risk of large symptomatic neurologic intracerebral hemorrhages. Importantly, CMBs are also currently regarded as markers of diffuse vascular and neurodegenerative brain damage. Thus, it is essential that we try to learn as much as we can about their development, evolution, and their relation to impaired cognition, dementia, and neurodegeneration.

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“…Insulin resistance (IR), brain insulin resistance (BIR), and MetS also result in brain remodeling (Figure 4) [26][27][28][29]. Additionally, T2DM is known to be associated with brain remodeling with cognitive impairment and dysfunction (CID) and EPVS [12,[30][31][32][33][34][35][36][37][38][39], and it is commonly accepted that age is the strongest risk factor for the development of EPVS, while hypertension, age plus hypertension, and diabetes were still three risk factors for those of 45 years old or under [40].…”

Section: Metabolic Disorders: Obesity Metabolic Syndrome (Mets) Type ...mentioning

confidence: 99%

Protoplasmic Perivascular Astrocytes Play a Crucial Role in the Development of Enlarged Perivascular Spaces in Obesity, Metabolic Syndrome, and Type 2 Diabetes Mellitus

Hayden

2023

Neuroglia

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Astrocytes (ACs) are the most abundant cells in the brain and, importantly, are the master connecting and communicating cells that provide structural and functional support for brain cells at all levels of organization. Further, they are recognized as the guardians and housekeepers of the brain. Protoplasmic perivascular astrocyte endfeet and their basal lamina form the delimiting outermost barrier (glia limitans) of the perivascular spaces in postcapillary venules and are important for the clearance of metabolic waste. They comprise the glymphatic system, which is critically dependent on proper waste removal by the pvACef polarized aquaporin-4 water channels. Also, the protoplasmic perisynaptic astrocyte endfeet (psACef) are important in cradling the neuronal synapses that serve to maintain homeostasis and serve a functional and supportive role in synaptic transmission. Enlarged perivascular spaces (EPVS) are emerging as important aberrant findings on magnetic resonance imaging (MRI), and are associated with white matter hyperintensities, lacunes, and aging, and are accepted as biomarkers for cerebral small vessel disease, increased obesity, metabolic syndrome, and type 2 diabetes. Knowledge is exponentially expanding regarding EPVS along with the glymphatic system, since EPVS are closely associated with impaired glymphatic function and waste removal from the brain to the cerebrospinal fluid and systemic circulation. This review intends to focus on how the pvACef play a crucial role in the development of EPVS.

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Association of Type 2 Diabetes Mellitus With Perivascular Spaces and Cerebral Amyloid Angiopathy in Alzheimer’s Disease: Insights From MRI Imaging

Cited by 9 publications

References 30 publications

A Closer Look at the Perivascular Unit in the Development of Enlarged Perivascular Spaces in Obesity, Metabolic Syndrome, and Type 2 Diabetes Mellitus

A Closer Look at the Perivascular Unit in the Development of Enlarged Perivascular Spaces in Obesity, Metabolic Syndrome, and Type 2 Diabetes Mellitus

Cerebral Microbleeds Associate with Brain Endothelial Cell Activation-Dysfunction and Blood-Brain Barrier Dysfunction-Disruption with an Increased Risk of Hemorrhagic and Ischemic Stroke That Is Capable of Exacerbating Neurodegeneration

Protoplasmic Perivascular Astrocytes Play a Crucial Role in the Development of Enlarged Perivascular Spaces in Obesity, Metabolic Syndrome, and Type 2 Diabetes Mellitus

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