Energy Metabolism and Cognitive Aging

Study Description

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Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

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.

Condition or disease	Intervention/treatment	Phase
Mild Cognitive Impairment	Other: Ketogenic diet; Other: Healthy high carbohydrate diet	Not Applicable

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.

Study Design

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Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Study Type :	Interventional (Clinical Trial)
Actual Enrollment :	62 participants
Allocation:	Randomized
Intervention Model:	Parallel Assignment
Intervention Model Description:	Parallel groups, randomized controlled nutritional intervention.
Masking:	None (Open Label)
Primary Purpose:	Prevention
Official Title:	Energy Metabolism and Cognitive Aging
Study Start Date :	September 1, 2008
Actual Primary Completion Date :	December 31, 2016
Actual Study Completion Date :	March 15, 2017

Arms and Interventions

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Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Arm	Intervention/treatment
Active Comparator: 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	Other: Healthy high carbohydrate diet; higher carbohydrate diet
Experimental: Carbohydrate restricted, ketogenic diet; Paricipants will follow a carbohydrate restricted dietary intervention designed to induce ketone metabolism	Other: Ketogenic diet; carbohydrate restricted diet

Outcome Measures

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Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Primary Outcome Measures :

1. improvement in memory testing [ Time Frame: 6 or 8 weeks ]

Secondary Outcome Measures :

1. correlation between diet, metabolic factors, memory performance, and cerebral activation [ Time Frame: 6 or 8 weeks ]

Eligibility Criteria

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Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Ages Eligible for Study:	50 Years and older (Adult, Senior)
Sexes Eligible for Study:	All
Accepts Healthy Volunteers:	No

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

Contacts and Locations

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Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Locations

United States, Ohio
University of Cincinnati
Cincinnati, Ohio, United States, 45219

Sponsors and Collaborators

University of Cincinnati

Investigators

Principal Investigator:	Robert Krikorian, PhD	University of Cincinnati

More Information

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Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Responsible Party:	Robert Krikorian, Professor, University of Cincinnati
ClinicalTrials.gov Identifier:	NCT00777010 History of Changes
Other Study ID Numbers:	04-09-17-01
First Posted:	October 22, 2008
Last Update Posted:	March 24, 2017
Last Verified:	March 2017
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD:	No

Keywords provided by Robert Krikorian, University of Cincinnati:

memory loss; mild cognitive impairment; forgetfulness

Additional relevant MeSH terms:

Cognitive Dysfunction; Cognition Disorders; Neurocognitive Disorders; Mental Disorders