Ketogenic Diet Improves Cognitive-Behavioral Function in a Mouse Model of Cerebral Amyloid Angiopathy

Abstract

Cerebral amyloid angiopathy (CAA), characterized by the accumulation of amyloid protein in cerebral vessels, is linked to Alzheimer's disease (AD), stroke, and cognitive impairment. Currently, there is no effective treatment or prevention for this condition. The ketogenic diet (KD), which is characterized by high fat, low carbohydrate, and moderate protein consumption, has gained considerable attention in recent years for its potential therapeutic use in patients with neurodegenerative diseases. Studies in AD rodent models have found that KD and/or ketogenic supplements attenuate cognitive-behavioral impairments and dementia-related pathology. However, it is unknown whether KD can similarly benefit individuals with CAA. Considering KD’s promising therapeutic outcomes in AD rodent models, this study sought to examine its effects in a transgenic CAA mouse model. Starting at ~3.5 months of age, male Tg-SwDI mice underwent a three-month dietary intervention with either a standard chow (14.4% fat, 26.1% protein, and 59.5% carbohydrates) or ketogenic diet (93.4% fat, 4.7% protein, and 1.8% carbohydrates). Mice were then subjected to a battery of behavioral tests to assess activity levels, cognitive function, and anxiety, along with metabolic tests to measure glucose and ketone body levels. KD resulted in nutritional ketosis, attenuated body weight and adiposity, lowered fasting glucose levels, improved glucose tolerance, increased physical activity, and enhanced spatial learning and memory. These findings provide compelling evidence that KD positively impacts cognitive performance, suggesting it may be a viable therapeutic option for CAA. Future research should explore the therapeutic potential of KD in females, as well as the diets' long-term efficacy.

Faculty Sponsors

Dr. Lisa Robinson

Project Type

Event

Location

Alvin Sherman Library

Start Date

4-3-2024 12:30 PM

End Date

4-4-2024 1:30 PM

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Ketogenic Diet Improves Cognitive-Behavioral Function in a Mouse Model of Cerebral Amyloid Angiopathy

Alvin Sherman Library

Cerebral amyloid angiopathy (CAA), characterized by the accumulation of amyloid protein in cerebral vessels, is linked to Alzheimer's disease (AD), stroke, and cognitive impairment. Currently, there is no effective treatment or prevention for this condition. The ketogenic diet (KD), which is characterized by high fat, low carbohydrate, and moderate protein consumption, has gained considerable attention in recent years for its potential therapeutic use in patients with neurodegenerative diseases. Studies in AD rodent models have found that KD and/or ketogenic supplements attenuate cognitive-behavioral impairments and dementia-related pathology. However, it is unknown whether KD can similarly benefit individuals with CAA. Considering KD’s promising therapeutic outcomes in AD rodent models, this study sought to examine its effects in a transgenic CAA mouse model. Starting at ~3.5 months of age, male Tg-SwDI mice underwent a three-month dietary intervention with either a standard chow (14.4% fat, 26.1% protein, and 59.5% carbohydrates) or ketogenic diet (93.4% fat, 4.7% protein, and 1.8% carbohydrates). Mice were then subjected to a battery of behavioral tests to assess activity levels, cognitive function, and anxiety, along with metabolic tests to measure glucose and ketone body levels. KD resulted in nutritional ketosis, attenuated body weight and adiposity, lowered fasting glucose levels, improved glucose tolerance, increased physical activity, and enhanced spatial learning and memory. These findings provide compelling evidence that KD positively impacts cognitive performance, suggesting it may be a viable therapeutic option for CAA. Future research should explore the therapeutic potential of KD in females, as well as the diets' long-term efficacy.