Aging and Cerebral Glucose Metabolism: 18F-FDG-PET/CT Reveals Distinct Global and Regional Metabolic Changes in Healthy Patients

Subtirelu, Robert Christopher; Teichner, Eric Michael; Su, Yvonne; Al-Daoud, Omar; Patel, Milan; Patil, Shiv; Writer, Milo; Werner, Thomas; Revheim, Mona-Elisabeth; Høilund-Carlsen, Poul Flemming; Alavi, Abass

doi:10.3390/life13102044

Cited by 8 publications

(2 citation statements)

References 41 publications

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“…First, we validated the 18 F-FDG PET/CT imaging technique to detect agerelated decreases in brain glucose uptake. In agreement with previous studies 51 , we were able to demonstrate a significant decrease in brain glucose uptake in aged animals compared with young controls (Suppl. Fig.…”

Section: Chronic β3ar Stimulation Improved Neurovascular Coupling Res...supporting

confidence: 93%

Chronic β3 adrenergic agonist treatment improves brain microvascular endothelial function and cognition in aged mice

Natarajan,

Ekambaram,

Tarantini

et al. 2024

Preprint

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Microvascular endothelial dysfunction, characterized by impaired neurovascular coupling, reduced glucose uptake, blood-brain barrier disruption, and microvascular rarefaction, plays a critical role in the pathogenesis of age-related vascular cognitive impairment (VCI). Emerging evidence points to non-cell autonomous mechanisms mediated by adverse circulating milieu (an increased ratio of pro-geronic to anti-geronic circulating factors) in the pathogenesis of endothelial dysfunction leading to impaired cerebral blood flow and cognitive decline in the aging population. In particular, age-related adipose dysfunction contributes, at least in part, to an unfavorable systemic milieu characterized by chronic hyperglycemia, hyperinsulinemia, dyslipidemia, and altered adipokine profile, which together contribute to microvascular endothelial dysfunction. Hence, in the present study, we aimed to test whether thermogenic stimulation, an intervention known to improve adipose and systemic metabolism by increasing cellular energy expenditure, could mitigate brain endothelial dysfunction and improve cognition in the aging population. Eighteen-month-old old C57BL/6J mice were treated with saline or CL (β3-adrenergic agonist) for 6 weeks followed by functional analysis to assess endothelial function and cognition. CL treatment improved neurovascular coupling responses and rescued brain glucose uptake in aged animals. In addition, CL treatment also attenuated blood-brain barrier leakage and associated neuroinflammation in the cortex of aged animals. More importantly, these beneficial changes in microvascular function translated to improved cognitive performance in radial arm water maze and Y-maze tests. Our results suggest that β3-adrenergic agonist treatment improves multiple aspects of brain microvascular endothelial function and can be potentially repurposed for treating age-associated cognitive decline.

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Section: Chronic β3ar Stimulation Improved Neurovascular Coupling Res...supporting

confidence: 93%

Chronic β3 adrenergic agonist treatment improves brain microvascular endothelial function and cognition in aged mice

Natarajan,

Ekambaram,

Tarantini

et al. 2024

Preprint

View full text Add to dashboard Cite

show abstract

“…In this study, the right caudate SUVR in ADD and ADND groups was significantly decreased compared with age-, gender-, and educational year-matched healthy controls, which suggested that right caudate may exhibit resistance to age-related functional decline. Typical 18 F-FDG PET findings in healthy controls have manifested reduced glucose metabolism in the frontal and temporal cortex, including lateral orbital gyrus, right temporopola, right orbitofrontal, left orbitofrontal gyrus, left dorsolateral frontal gyrus, and left insula areas ( Kim et al, 2009 ; Subtirelu et al, 2023 ). These studies indicated that the right caudate may be more susceptible to neuropsychiatric symptoms, which further leads to the reduction in the metabolic function by affecting the circuit function, and may be closely related to the cognitive impairment in ADD patients.…”

Section: Discussionmentioning

confidence: 99%

The mediating effect of 18F-FDG metabolism in right caudate between depressive symptoms and cognitive function in Alzheimer’s disease

Wang,

Cui,

Chen

et al. 2024

Front. Aging Neurosci.

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PurposeThe objective of this study was to investigate the accumulation of 18F-fluorodeoxyglucose (18F-FDG) in the whole brain between Alzheimer’s disease (AD) with depressive (ADD) symptoms compared with AD without depressive (ADND) symptoms using positron emission tomography/magnetic resonance imaging (PET/MRI). Additionally, this study aimed to explore the associations among the accumulation of 18F-FDG in the brain, depressive symptoms, and cognitive function in ADD patients.MethodsIn this study, 25 AD patients and 22 healthy controls were enrolled. The AD patients were stratified into two groups, namely ADD and ADND, based on their scores of the Hamilton Depression Scale (HAMD). Both AD patients and healthy controls underwent an 18F-FDG PET/MRI scan. A standardized uptake value ratio (SUVR) was calculated to examine the accumulation of 18F-FDG in the brain. A simple mediation model was employed to examine the mediation effect between SUVR, depressive symptoms and cognitive function in ADD patients.ResultsThe ADD group exhibited significant cognitive impairment compared to the ADND group (p < 0.001) and healthy controls (p < 0.001). The ADD patients exhibited the reduced SUVR (0.228 ± 0.126) in the right caudate (the voxel level p < 0.005, cluster level p < 0.05, after false discovery rate (FDR) correction) compared to ADND patients (0.459 ± 0.064) and healthy controls (0.706 ± 0.122). The SUVR of the right caudate was correlated with the HAMD scores (r = −0.792, p < 0.001) and mini-mental state examination (MMSE) (r = 0.738, p < 0.01). The relationship between depressive symptoms and the cognitive function in ADD patients is mediated by the right caudate SUVR (total effects = −0.385, direct effects = −0.02, total indirect effects = −0.405).ConclusionThe ADD group exhibited the reduced SUVR in the right caudate compared to the ADND group and healthy controls. The relationship between depressive symptoms and the cognitive ability of AD patients was mediated by the right caudate SUVR. The results contribute to a deeper understanding of the neurobiological mechanisms related to AD with depressive symptoms.

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Metabolic Status Modulates Global and Local Brain Age Estimates in Overweight and Obese Adults

Haas,

Abbasi,

Watson

et al. 2024

Biological Psychiatry: Cognitive Neuroscience and Neuroimaging

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Aging and Cerebral Glucose Metabolism: 18F-FDG-PET/CT Reveals Distinct Global and Regional Metabolic Changes in Healthy Patients

Cited by 8 publications

References 41 publications

Chronic β3 adrenergic agonist treatment improves brain microvascular endothelial function and cognition in aged mice

Chronic β3 adrenergic agonist treatment improves brain microvascular endothelial function and cognition in aged mice

The mediating effect of 18F-FDG metabolism in right caudate between depressive symptoms and cognitive function in Alzheimer’s disease

Metabolic Status Modulates Global and Local Brain Age Estimates in Overweight and Obese Adults

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