HomeDiseaseContrasting Metabolic Insufficiency in Aging and Dementia

Contrasting Metabolic Insufficiency in Aging and Dementia

December 5, 2021

Aging Dis. 2021 Jul 1;12(4):1081-1096. doi: 10.14336/AD.2021.0104. eCollection 2021 Jul.

ABSTRACT

Metabolic insufficiency and neuronal dysfunction occur in normal aging but is exaggerated in dementia and Alzheimer’s disease (AD). Metabolic insufficiency includes factors important for both substrate supply and utilization in the brain. Metabolic insufficiency occurs through a number of serial mechanisms, particularly changes in cerebrovascular supply through blood vessel abnormalities (ie, small and large vessel vasculopathy, stroke), alterations in neurovascular coupling providing dynamic blood flow supply in relation to neuronal demand, abnormalities in blood brain barrier including decreased glucose and amino acid transport, altered glymphatic flow in terms of substrate supply across the extracellular space to cells and drainage into CSF of metabolites, impaired transport into cells, and abnormal intracellular metabolism with more reliance on glycolysis and less on mitochondrial function. Recent studies have confirmed abnormal neurovascular coupling in a mouse model of AD in response to metabolic challenges, but the supply chain from the vascular system into neurons is disrupted much earlier in dementia than in equivalently aged individuals, contributing to the progressive neuronal degeneration and cognitive dysfunction associated with dementia. We discuss several metabolic treatment approaches, but these depend on characterizing patients as to who would benefit the most. Surrogate biomarkers of metabolism are being developed to include dynamic estimates of neuronal demand, sufficiency of neurovascular coupling, and glymphatic flow to supplement traditional static measurements. These surrogate biomarkers could be used to gauge efficacy of metabolic treatments in slowing down or modifying dementia time course.

PMID:34221551 | PMC:PMC8219502 | DOI:10.14336/AD.2021.0104

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About The Author

Patrick Blanchard MD

Meet Dr. Blanchard Dr. Blanchard’s medical practice is an embodiment of Integrative health which brings conventional and complementary approaches together in a coordinated way. Conveniently located in sunny Florida and over the internet with ValiseMD’s secure HIPPA compliant telXmed servers. Since 1994, patients with a wide range of challenging medical problems have achieved optimum health using the best of natural medicine, judiciously combined with high-tech innovations. Breakthroughs are often achieved even after patients have consulted mainstream specialists and holistic practitioners. Dr. Blanchard is founder and CEO of ValiseMD, Inc. He is board certified in Family Medicine since 1994 and awarded Fellow of the American Academy of Family Physicians in 2001. He received the ‘Teacher of the Year’ award from the University of Kansas School of Medicine at completion of his residency in Family Medicine. He completed a fellowship at Wake Forest University in the field of vascular neurosonology. He holds a medical patent in the field of Gastroenterology. He holds an unrestricted license to practice medicine and surgery in Florida. He started his medical career as a Emergency Medical Technician, then as a Paramedic and later a Medical Doctor.