Effects of Weight Loss Management on Cognitive Function in Elderly Women With Obesity

Study Overview
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Brief Summary
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According to studies, the risk of cerebrovascular disease and cognitive decline are associated with age-related changes. In addition, there is data suggesting a relationship between the progression of this pathology and the presence of obesity and associated metabolic disorders. According to to some research, weight loss associated with cognitive function decline. In this regard, the development of effective, applicable in real clinical practice methods of non-drug treatment and prevention of cerebrovascular disorders and age-related cognitive decline in people with obesity and metabolic disorders, who are at high risk, seems to be extremely relevant. The main goal of the study is to compare the effectiveness of various weight loss approaches and to study their effects on the cognitive functions of elderly obesity women.

Detailed Description
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The high prevalence of comorbid pathology characterised the elderly and senile population. Particularly, comorbid condition is often based on obesity. Also, an important characteristic of the elderly and senile age is the development of age-related cognitive deficit and progressive decline in cognitive functions, that is detected in 60.8% of people over 65 years old in Russia according to the EVKALIPT study. The prevalence of obesity in the Russian population reaches 40% among the elderly population. According to studies, the presence of obesity is paradoxically associated with less progression of cognitive function loss, and the risk reduction in some populations reaches 40%. However, the sarcopenic obesity is an independent predictor of cognitive impairment in the elderly. Consequently, the therapy of obesity in elderly and senile population faces two important aspects: the risk of muscle loss and the development of sarcopenia and progressive cognitive decline. The described features of this age group are consistent with the well-known obesity paradox, in which overweight and obesity are associated with longer life expectancy. The risk of muscle mass reduction and cognitive functions decrease determines the formation of a specialised approach to obesity management in older population. Thus, the setting of softer and longer-term goals with a gradual decrease in body weight is typical. Studies have considered the use of various interventions, so far the combination of diet with exercise has proven effectiveness in muscle mass protection. At the same time, regular exercises reliably protect from cognitive decline. Thereby, the combination of diet and physical activity is considered as a suitable approach to obesity management in the elderly. Recently, there have also been a number of studies evaluating the effectiveness of the ketogenic diet. This diet pattern is reliably effective in body weight reduction, skeletal muscle mass maintenance, and adipose tissue metabolism improvement in the elderly . Also, the neuroprotective effects of the ketogenic diet have been confirmed by meta-analyses and have made it possible to include it in current guidelines for the prevention and treatment of cognitive impairment. However, the high frequency of negative effects and the associated low adherence limit the possibilities of using this diet, which led to the development of exogenous ketones that allow reaching the levels of blood ketone bodies associated with neuroprotective properties (0.2-0.5 mmol/l) with better portability. The main goal of the study is to compare the effectiveness of various weight loss approaches and to study their effects on the cognitive functions of elderly obesity women.

Official Title
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Effects of Weight Loss Management on Cognitive Function in Elderly Obese Women

Conditions
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Obesity, Cognitive Change

Intervention / Treatment
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* Dietary Supplement: PanTrek
* Behavioral: Physical Trainings
* Other: Placebo
* Behavioral: Diet


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Female; Age 60 and over; BMI 30.0 kg/m2 or more. Exclusion Criteria: Male; age under 60; BMI <30.0 kg/m2; patients unable or unwilling to comply with the requirements of the protocol, including the signing of informed consent (inability to give such consent due to mental deficiency or language barrier), as well as non-compliance with the schedule of visits, persons unable to independently make a decision and sign an informed consent; less than 6 months after suffering cardiovascular events, stroke, severe surgical interventions and injuries; alcohol abuse (including chronic pancreatitis of alcoholic etiology) or drug addiction at present or within the last 5 years; history of malignant diseases, regardless of the treatment during the last 5 years; less than 4 weeks after suffering acute infectious and / or inflammatory diseases, after the onset of complete clinical and laboratory remission; pregnancy and lactation; history of allergic reactions to components of the study product and/or placebo or intolerance to components of the study product and/or placebo.

Ages Eligible for Study
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Minimum Age: 60 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Other
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Prospective randomised parallel arms double control interventional study
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: The Product Group<br>The Product group is prescribed with the investigated product - exogeneous ketone bodies. | Dietary Supplement: PanTrek<br>* The intervention is represented by the investigational product PanTrek, shots with liquid, 25 ml each (TU 10.89.19-01-44850857-2020). The composition of the product PanTrek (per 1 dose): Ginseng dry extract (Panax ginseng Meyer) all parts of the plant - 125 mg (the amount of ginsenosides in one vial is 9.0 mg ± 3.5 mg); Melissa officinalis dry extract (Melissa officinalis L) all parts of the plant - 340 mg (the amount of hydroxycinnamic acids is 19.50 mg / vial ± 10% in one vial); Apple juice concentrated 2.5% - 7,5 g; Potassium beta-hydroxybutyrate - 4,5 g; Magnesium beta-hydroxybutyrate - 500 mg; E211 sodium benzoate - no more than 5 mg; E202 Potassium sorbate - no more than 3,6 mg; Water purified - up to 25 ml. The product has registered as diet supplement in the Unified Register of Certificates of State Registration N RU.77.99.11.003.R.001152.04.21 from 05.04.2021.<br>* Other names: Exogenous ketone bodies;|
| Active Comparator: The Combined Intervention Group<br>The Combined Intervention Group is prescribed with the investigated product -in combination with regular physical trainings. | Dietary Supplement: PanTrek<br>* The intervention is represented by the investigational product PanTrek, shots with liquid, 25 ml each (TU 10.89.19-01-44850857-2020). The composition of the product PanTrek (per 1 dose): Ginseng dry extract (Panax ginseng Meyer) all parts of the plant - 125 mg (the amount of ginsenosides in one vial is 9.0 mg ± 3.5 mg); Melissa officinalis dry extract (Melissa officinalis L) all parts of the plant - 340 mg (the amount of hydroxycinnamic acids is 19.50 mg / vial ± 10% in one vial); Apple juice concentrated 2.5% - 7,5 g; Potassium beta-hydroxybutyrate - 4,5 g; Magnesium beta-hydroxybutyrate - 500 mg; E211 sodium benzoate - no more than 5 mg; E202 Potassium sorbate - no more than 3,6 mg; Water purified - up to 25 ml. The product has registered as diet supplement in the Unified Register of Certificates of State Registration N RU.77.99.11.003.R.001152.04.21 from 05.04.2021.<br>* Other names: Exogenous ketone bodies;Behavioral: Physical Trainings<br>* Physical activity is represented by 2 workouts lasting 45 minutes per week on an antigravity treadmill Alter-G M320 (AlterG, USA) and 2 sessions of reoxygenation lasting 30 minutes on a normobaric hypoxic therapy device ReOxy (Bitmos GmbH, Germany).<br>* Other names: Exercises;|
| Placebo Comparator: The Placebo Group<br>The Placebo Group is prescribed with the Placebo. | Other: Placebo<br>* The placebo is represented by concentrated apple juice 2.5% - 7.5 g, potassium chloride - 2.405 g, MgCl2 - 0.382 g, sodium benzoate (E211) - 5 mg and potassium sorbate (E202) - 3.6 mg, brought to 25 ml of distilled water.<br>|
| Active Comparator: The Diet Group<br>The Diet Group is prescribed with the Diet designed with 500 kcal reduction from daily energy expenditure. | Behavioral: Diet<br>* The studied diet is a low-calorie diet with an average energy value of 1730.16 kcal / day and a certain chemical composition (proteins - 108.80 g / day, fats - 68.10 g / day, carbohydrates - 162.60 g / day), including the main groups products (meat and poultry dishes, fish dishes, dairy products, cereals, vegetables and fruits). On average, 0.96-1.05 g of protein accounted for 1 kg of body weight of the subjects.<br>|
| No Intervention: The Control Group<br>The Control Group is prescribed with standard recommendations for weight loss. | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from baseline body weight at 12 weeks | The dynamics of body weight | Baseline (visit 1) and after 12 weeks (visit 2) | 
| Change from baseline Montreal Cognitive Assessment (MoCa) test scores at 12 weeks | The changes in the cognitive testing results | Baseline (visit 1) and after 12 weeks (visit 2) | 
| Change from baseline Trail Making Test (TMT) a&b test scores at 12 weeks | The changes in the cognitive testing results (normal range - less than 78 and 273 seconds (=scores)). | Baseline (visit 1) and after 12 weeks (visit 2) | 
| Change from baseline Word recall test scores at 12 weeks | The changes in the cognitive testing results (normal range as 45 words (=scores) and more out of 5 repetitions). Minimal - 0 (worse result), maximal score - 50 (excellent result). | Baseline (visit 1) and after 12 weeks (visit 2) | 
| Change from baseline Mean response time in the test Schulte tables at 12 weeks | The changes in the cognitive testing results | Baseline (visit 1) and after 12 weeks (visit 2) | 
| Change from baseline The Stroop Color and Word Test results at 12 weeks | The changes in the cognitive testing results | Baseline (visit 1) and after 12 weeks (visit 2) | 
| Change from baseline Verbal fluency test results at 12 weeks | The changes in the cognitive testing results | Baseline (visit 1) and after 12 weeks (visit 2) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from baseline fat mass at 12 weeks | The changes in the fat mass according to the bioimpedance analysis | Baseline (visit 1) and after 12 weeks (visit 2) | 
| Change from baseline skeletal muscle mass at 12 weeks | The changes in the skeletal muscle mass according to the bioimpedance analysis | Baseline (visit 1) and after 12 weeks (visit 2) | 
| Change from baseline visceral fat at 12 weeks | The changes in visceral fat according to the bioimpedance analysis | Baseline (visit 1) and after 12 weeks (visit 2) | 
| Change from baseline total cholesterol serum levels at 12 weeks | The changes of total cholesterol serum levels | Baseline (visit 1) and after 12 weeks (visit 2) | 
| Change from baseline LDL-cholesterol serum levels at 12 weeks | The changes of LDL-cholesterol serum levels | Baseline (visit 1) and after 12 weeks (visit 2) | 
| Change from baseline HOMA-IR (homeostasis model assessment - insulin resistance) index at 12 weeks | The changes of HOMA-IR index | Baseline (visit 1) and after 12 weeks (visit 2) | 
| Change from baseline C-reactive protein (CRP) serum levels at 12 weeks | The changes of CRP serum levels | Baseline (visit 1) and after 12 weeks (visit 2) | 
| Change from baseline Tumor Necrosis Factor Alpha (TNFa) serum levels at 12 weeks | The changes of TNFa serum levels | Baseline (visit 1) and after 12 weeks (visit 2) | 
| Change from baseline systolic blood pressure (SBP) at 12 weeks | The changes of SBP | Baseline (visit 1) and after 12 weeks (visit 2) | 
| Change from baseline diastolic blood pressure (DBP) at 12 weeks | The changes of DBP | Baseline (visit 1) and after 12 weeks (visit 2) | 
| Change from baseline grip strength at 12 weeks | The changes of grip strength measured by grip dynamometer on the leading hand | Baseline (visit 1) and after 12 weeks (visit 2) | 
| Change from baseline Six Minute Walk Test distance at 12 weeks | The changes of Six Minute Walk Test results | Baseline (visit 1) and after 12 weeks (visit 2) | 
| Change from baseline Hamilton Anxiety Rating Scale at 12 weeks | The changes of Hamilton Anxiety Rating Scale results (normal range - 6 scores and less). | Baseline (visit 1) and after 12 weeks (visit 2) | 
| Change from baseline Hamilton Depression Rating Scale at 12 weeks | The changes of Hamilton Depression Rating Scale results (normal range - 7 scores and less). | Baseline (visit 1) and after 12 weeks (visit 2) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Elderly, Obesity, Weight loss, Cognitive Change, Exogenous Ketones, Diet, Physical activity