Energy Metabolism and Cognitive Aging

NCT ID: NCT00777010

Last Updated: 2017-03-24

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: NA
• Total Enrollment: 62 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2008-09-01
• Study Completion Date: 2017-03-15

Brief Summary

Participants 60 and older with and without Parkinson's disease who have mild cognitive decline will be randomized to either a standard higher carbohydrate diet or a carbohydrate-restricted ketogenic diet for 8 weeks. The main hypothesis is that nutritional ketosis will improve memory functioning. Pre and post-memory testing will be performed. Subjects will also provide blood samples and a subset of subjects with receive magnetic resonance brain imaging.

Detailed Description

Obesity and metabolic disturbance are recognized as important risks for disorders such as cardiovascular disease, stroke, and cancer. However, these conditions also contribute to age-related cognitive decline and dementia. In particular, insulin resistance and hyperinsulinemia promote neurocognitive dysfunction and neurodegenerative changes during the extended pre-clinical phase of Alzheimer's disease (AD). The prevalence of both metabolic disturbance and dementia are increasing dramatically, and in the absence of effective treatment, preventive approaches are essential to address the ominous public health concern represented by Alzheimer's disease and other forms of dementia. Dietary intervention is a promising and under-investigated preventive option. Regimens involving restricted carbohydrate consumption designed to induce ketone metabolism have been shown to improve metabolic parameters. In addition, ketone metabolism is associated with a host of benefits for neural function, among them enhanced mitochondrial energy production and reduction of neuropathological factors. Ketone feeding studies have demonstrated acute functional improvement in older adults with neurocognitive decline.

This research is designed to assess the efficacy of strict carbohydrate restriction in correcting hyperinsulinemia and improving neurocognitive function in older adults with early memory decline. Recently, we have shown that relatively brief intervention involving a low carbohydrate, ketogenic diet can improve memory in subjects with Mild Cognitive Impairment. We would like to extend these initial findings by adding new study arms involving older adult subjects with Parkinson's disease and Mild Cognitive Impairment. We also will increase the intervention period from six weeks to eight weeks.

Aim 1: To evaluate the effect of adaptation to ketosis on cognitive function in older adults with Age-Associated Memory Impairment (AAMI) and Mild Cognitive Impairment (MCI).

Hypothesis 1. Subjects with AAMI and MCI will show improved working memory and long-term memory ability after practicing a low carbohydrate, ketogenic diet for six weeks relative to comparison subjects who maintain a typical, high carbohydrate, nonketogenic diet.

Aim 2: To assess the effect of ketone metabolism on memory and motor function in subjects with Parkinson's disease and Mild Cognitive Impairment after eight (8) weeks of dietary intervention.

Hypothesis 2. Subjects with Parkinson's disease and MCI will show improved working memory and long-term memory function after practicing a low carbohydrate, ketogenic diet for eight weeks relative to comparison subjects who consume a typical, high carbohydrate nonketogenic diet.

Hypothesis 3. Subjects with Parkinson's disease and MCI will show improved motor function after practicing a low carbohydrate, ketogenic diet for eight weeks relative to comparison subjects who consume a typical, high carbohydrate nonketogenic diet.

We also will evaluate changes in mood, ketone body levels, serum lipids, inflammatory markers, and fasting glucose and insulin and assess relationships of these factors with the primary outcome measures. We will obtain diet records during the intervention to assess adherence to the protocol.

Conditions

Mild Cognitive Impairment

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: PREVENTION
• Blinding Strategy: NONE

Study Groups

Healthy high carbohydrate diet

Participants will follow a typical, higher carbohydrate dietary intervention with emphasis on lower glycemic carbohydrate foods and monounsaturated fatty acid consumption

Group Type: ACTIVE_COMPARATOR

Healthy high carbohydrate diet

Intervention Type: OTHER

higher carbohydrate diet

Carbohydrate restricted, ketogenic diet

Paricipants will follow a carbohydrate restricted dietary intervention designed to induce ketone metabolism

Group Type: EXPERIMENTAL

Ketogenic diet

Intervention Type: OTHER

carbohydrate restricted diet

Interventions

Ketogenic diet

carbohydrate restricted diet

Intervention Type: OTHER

Healthy high carbohydrate diet

higher carbohydrate diet

Intervention Type: OTHER

Eligibility Criteria

Inclusion Criteria

• Age 60 years or older
• Mild cognitive impairment

Exclusion Criteria

• Diabetes
• Medications that have effect on memory
• Memory problems due to medical issues (ie head injury, stroke, untreated sleep apnea etc.)
• Unable to complete an MRI scan

• Minimum Eligible Age: 50 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

University of Cincinnati

OTHER

Sponsor Role: lead

Responsible Party

Robert Krikorian

Professor

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Robert Krikorian, PhD

Role: PRINCIPAL_INVESTIGATOR

University of Cincinnati

Locations

University of Cincinnati

Cincinnati, Ohio, United States

Countries

United States

Other Identifiers

04-09-17-01

Identifier Type: -

Identifier Source: org_study_id