Mitochondrial dysfunction and cognitive impairment are common symptoms in many neurologic and psychiatric disorders, as well as nonpathological aging. Ketones have been suggested as therapeutic for their efficacy in epilepsy and other brain pathologies such as Alzheimer’s disease and major depressive disorder. However, their effects on cognitive function in healthy individuals is less established. Here, we explored the mitochondrial and performative outcomes of a novel eight-week ketone-supplemented ketogenic (KETO) diet in healthy adult male and female mice. In a novel object recognition test, KETO mice spent more time with the novel, compared to familiar, object, indicating an improvement in recognition memory. High-resolution respirometry on permeabilized hippocampal tissue returned significant reductions in mitochondrial O₂ consumption. No changes in ATP production were observed, yielding a significantly higher ATP:O₂ ratio, a measure of mitochondrial efficiency. Together, these findings demonstrate the KETO diet improves hippocampal mitochondrial efficiency. They add to a growing body of evidence that suggests ketones and ketogenic diets are neuroprotective and metabolically and cognitively relevant, even in healthy adults. They also suggest that ketogenic lifestyle changes may be effective strategies for protecting against cognitive decline associated with aging and disease.

Alzheimer’s disease (AD) is the most common form of neurodegenerative disease worldwide. A large body of work implicates insulin resistance in the development and progression of AD. Moreover, impairment in mitochondrial function, a common symptom of insulin resistance, now represents a fundamental aspect of AD pathobiology. Ceramides are a class of bioactive sphingolipids that have been hypothesized to drive insulin resistance. Here, we describe preliminary work that tests the hypothesis that hyperinsulinemia pathologically alters cerebral mitochondrial function in AD mice via accrual of the ceramides. Homozygous male and female ApoE4 mice, an oft-used model of AD research, were given chronic injections of PBS (control), insulin, myriocin (an inhibitor of ceramide biosynthesis), or insulin and myriocin over four weeks. Cerebral ceramide content was assessed using liquid chromatography–mass spectrometry. Mitochondrial oxygen consumption rates were measured with high-resolution respirometry, and H₂O₂ emissions were quantified via biochemical assays on brain tissue from the cerebral cortex. Significant increases in brain ceramides and impairments in brain oxygen consumption were observed in the insulin-treated group. These hyperinsulinemia-induced impairments in mitochondrial function were reversed with the administration of myriocin. Altogether, these data demonstrate a causative role for insulin in promoting brain ceramide accrual and subsequent mitochondrial impairments that may be involved in AD expression and progression.

Alzheimer’s disease (AD) is the most common form of neurodegenerative disease worldwide. A large body of work implicates insulin resistance in the development and progression of AD such that AD may be a form of brain insulin resistance. Moreover, impairment in mitochondrial function, a common symptom of insulin resistance, now represents a fundamental aspect of AD pathobiology. Ceramides are a class of bioactive sphingolipids that have been hypothesized to drive insulin resistance. Here we describe preliminary work that tests the hypothesis that hyperinsulinemia pathologically alters cerebral mitochondrial function in AD mice via accrual of the ceramides. Homozygous male and female ApoE4 mice were given chronic injections of PBS (control), insulin, myriocin (an inhibitor of ceramide biosynthesis), or insulin and myriocin over four weeks. Cerebral ceramide content was assessed using liquid chromatography-mass spectrometry. Mitochondrial oxygen consumption rates were measured with high-resolution respirometry, and H2O2 emissions were quantified via biochemical assays on brain tissue from the cerebral cortex. Significant increases in brain ceramides and impairments in brain oxygen consumption were observed in the insulin-treated group. These hyperinsulinemia-induced impairments in mitochondrial function were reversed with the administration of myriocin. Altogether, these data demonstrate a causative role for insulin in promoting brain ceramide accrual and subsequent mitochondrial impairments that may be involved in AD expression and progression.

Background/Objectives: Hearing loss affects over 1.57 billion people worldwide, and many who could benefit from hearing aids do not wear them. Poor speech understanding in noise is one of the main complaints, and several artificial intelligence (AI) models have been proposed to address it. This review aims to characterize AI applications in hearing devices and offers a framework for advancing from model development to clinical application. Methods: Following PRISMA-ScR guidelines, PubMed/MEDLINE, Embase, CINAHL, Web of Science, and APA PsycInfo were searched for peer-reviewed original studies published from 2010 to 2025. Data regarding AI task, architecture, input, training method, validation, and latency were collected for each model. Results: In total, 46 studies met the inclusion criteria. Speech enhancement was the most common task (58.7%), and deep neural networks were the most common architecture (34.8%). Training was predominantly offline (93.5%) and supervised (91.3%). Validation relied mainly on database/simulation (71.7%) and normal-hearing listeners (39.1%); only 1 model (2.2%) was validated using hearing-impaired listeners in real-world conditions. Ten models (21.7%) met the latency requirements for hearing aid use. Conclusions: AI has been applied across many hearing device tasks, but most models remain early in development. Clinical translation will require on-device implementation and real-world validation in hearing-impaired listeners.