Lifestyle and Brain Vascular Function

The Effects of a Healthy Lifestyle Intervention on Brain Vascular Function in Older People

Cognitive performance is negatively related to an impaired glucose metabolism, possibly due to impairments in brain vascular function. Supported by the statement from the American Heart and Stroke Association that a healthy lifestyle is one of the most effective strategies to protect against cognitive decline, the investigators now hypothesise that healthy lifestyle intervention-induced changes in glucose metabolism cause beneficial effects on brain vascular function thereby improving cognitive performance. The primary objective of this intervention study is thus to evaluate in sedentary older men and women the effect of a 16-week aerobic-based exercise program on cerebral blood flow, as quantified by the non-invasive gold standard magnetic resonance imaging (MRI) perfusion method Arterial Spin Labeling (ASL). Cerebral blood flow is a robust and sensitive physiological marker of brain vascular function. Secondary objectives are to examine effects on glucose metabolism using the homeostatic model assessment for insulin resistance (HOMA-ir) and cognitive performance as assessed with a neurophysiological test battery.

Study Overview

• Status: Terminated
• Conditions: Cerebral Blood Flow; Healthy Diet; Cognitive Performance; Glucose Metabolism; Healthy Lifestyle; Physical Exercise; Cerebrovascular Circulation
• Intervention / Treatment: Other: Healthy Lifestyle

• Study Type: Interventional
• Enrollment (Actual): 10
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Netherlands
  • Limburg
    • Maastricht, Limburg, Netherlands, 6229 ER
      • Maastricht University Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 55 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• BMI between 25-35 kg/m2
• Sedentary (assessed as low physically active using the International Physical Activity Questionnaire)
• Right handedness and footedness
• Fasting plasma glucose < 7.0 mmol/L
• Fasting serum total cholesterol < 8.0 mmol/L
• Fasting serum triacylglycerol < 4.5 mmol/L
• Systolic blood pressure < 160 mmHg and diastolic blood pressure < 100 mmHg
• Stable body weight (weight gain or loss < 3 kg in the past three months)
• Willingness to give up being a blood donor from 8 weeks before the start of the study, during the study and for 4 weeks after completion of the study
• No difficult venipuncture as evidenced during the screening visit

Exclusion Criteria:

• Current smoker, or smoking cessation < 12 months
• Diabetic patients
• Familial hypercholesterolemia
• Abuse of drugs
• Consumption of more than 21 alcoholic units/week (men), or more than 14 alcoholic units/week (women)
• Use of dietary supplements known to interfere with the main study outcomes as judged by the principal investigators
• Use medication to treat blood pressure, lipid or glucose metabolism
• Use of an investigational product within another biomedical intervention trial within the previous 1-month
• Severe medical conditions that might interfere with the study, such as epilepsy, asthma, kidney failure or renal insufficiency, chronic obstructive pulmonary disease, inflammatory bowel diseases, auto inflammatory diseases and rheumatoid arthritis
• Active cardiovascular disease like congestive heart failure or cardiovascular event, such as an acute myocardial infarction or cerebrovascular accident
• Contra-indications for MRI imaging, including permanent facial makeup, surgical clips/material in body, metal splinter in eye or claustrophobia

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Healthy lifestyle; Healthy lifestyle intervention, which includes physical activity and dietary advice according to the dutch guidelines.	Other: Healthy Lifestyle; The physical activity guidelines for older consist of 150 minutes per week moderate-to-high intensity exercise, two times per week muscle and bone strengthening exercises, which are combined with balance exercises. Additional health benefits can be achieved with a longer exercise duration, frequency and/or intensity. Furthermore, the amount of time sitting should be minimised. The dietary guidelines are described in detail in the so-called "The Wheel of Five". In brief, the circle is divided into four food groups and one beverage group. More than half of the circle is covered by fruits, vegetables, whole grain (containing) breads, cereals and potatoes. A much smaller part is compromised by animal source foods, spreads and cooking fats. Water, tea and coffee without sugar complete the circle.
No Intervention: Control; Maintenance of habitual physical activity and diet

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Brain vascular function	Cerebral blood flow as quantified non-invasively by the MRI perfusion method Arterial Spin Labeling (ASL)	Baseline (0 weeks)
Brain vascular function	Cerebral blood flow as quantified non-invasively by the MRI perfusion method Arterial Spin Labeling (ASL)	After intervention (16 weeks)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Cognitive performance	Cambridge Neuropsychological Test Automated Battery (CANTAB)	Baseline (0 weeks) and after intervention (16 weeks)
Glucose metabolism	Homeostatic Model Assessment for Insulin Resistance (HOMA-ir) and HbA1c	Baseline (0 weeks), at the middle (8 weeks) and after intervention (16 weeks)

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Flow-Mediated Vasodilation (FMD)	Peripheral vascular function, endothelial function	Baseline (0 weeks) and after intervention (16 weeks)
Carotid Artery Reactivity (CAR)	Peripheral vascular function, endothelial function	Baseline (0 weeks) and after intervention (16 weeks)
Pulse Wave Analysis (PWA)	Peripheral vascular function, vascular stiffness	Baseline (0 weeks) and after intervention (16 weeks)
Pulse Wave Velocity (PWV)	Peripheral vascular function, vascular stiffness	Baseline (0 weeks) and after intervention (16 weeks)
Retinal microvascular calibers	Peripheral vascular function, microcirculation	Baseline (0 weeks) and after intervention (16 weeks)
Blood pressure (systolic, diastolic and mean pressure)	Office and 24-hour ambulatory blood pressure	Baseline (0 weeks) and after intervention (16 weeks)
Serum lipid profile concentration	Concentration of serum lipids	Baseline (0 weeks), at the middle (8 weeks) and after intervention (16 weeks)
Serum insulin concentration	Concentration of insulin in serum	Baseline (0 weeks), at the middle (8 weeks) and after intervention (16 weeks)
Plasma glucose concentration	Concentration of glucose in plasma	Baseline (0 weeks), at the middle (8 weeks) and after intervention (16 weeks)
Homeostatic Model Assessment for Insulin Resistance (HOMA-ir)	HOMA-ir is a method used to quantify insulin resistance and beta-cell function	Baseline (0 weeks), at the middle (8 weeks) and after intervention (16 weeks)
Circulating markers for low-grade systemic inflammation	Markers for low-grade systemic inflammation (IL-6, TNF-alpha)	Baseline (0 weeks), at the middle (8 weeks) and after intervention (16 weeks)
Circulating markers for microvascular function	Markers for microvascular function (sCAM-1, vWf, cGMP)	Baseline (0 weeks), at the middle (8 weeks) and after intervention (16 weeks)
Circulating marker of neurogenesis	Brain-derived neurotrophic factor (BDNF)	Baseline (0 weeks), at the middle (8 weeks) and after intervention (16 weeks)
Glycated haemoglobin (HbA1C)	HbA1C is a form of hemoglobin (abbreviated Hb) that is chemically linked to a sugar.	Baseline (0 weeks) and after intervention (16 weeks)
Aerobic fitness	Incremental exhaustive exercise test (Maximal oxygen consumption and power output)	Baseline (0 weeks), at the middle (8 weeks) and after intervention (16 weeks)
Physical fitness (1)	Incremental exhaustive exercise test (Maximal Power output)	Baseline (0 weeks), at the middle (8 weeks) and after intervention (16 weeks)
Physical fitness (2)	The 6-minute walk test (6 MWT)	Baseline (0 weeks) and after intervention (16 weeks)
Activity monitoring	activPAL activity monitor	Baseline (0 weeks) and after intervention (16 weeks) for four consecutive days
Self reported physical activity	The International Physical Activity Questionnaire	Baseline (0 weeks), at the middle (8 weeks) and after intervention (16 weeks)
Food frequency questionnaire	Self reported food consumption	Baseline (0 weeks), at the middle (8 weeks) and after intervention (16 weeks)
Dutch Healthy Diet index 2015	Compliance to the Dutch dietary guidelines based on the FFQ	Baseline (0 weeks), at the middle (8 weeks) and after intervention (16 weeks)
Quality of Life score	The Quality of life will be assessed using a 32-item questionnaire	Baseline (0 weeks) and after intervention (16 weeks)
Sleep characteristics	Sleep characteristics will be assessed using the 10-item Pittsburgh Sleep Quality Index	Baseline (0 weeks) and after intervention (16 weeks)
Fat mass	Body composition measured with whole body air-displacement by the BodPod	Baseline (0 weeks) and after intervention (16 weeks)
Fat free mass	Body composition measured with whole body air-displacement by the BodPod	Baseline (0 weeks) and after intervention (16 weeks)
Anthropometrics (1)	Weight	Baseline (0 weeks) and after intervention (16 weeks)
Anthropometrics (2)	BMI	Baseline (0 weeks), at the middle (8 weeks) and after intervention (16 weeks)
Anthropometrics (3)	Waist and hip circumference (ratio)	Baseline (0 weeks), at the middle (8 weeks) and after intervention (16 weeks)
Structural brain status (1)	MRI MPRAGE	Baseline (0 weeks) and after intervention (16 weeks)
Structural brain status (2)	T2FLAIR	Baseline (0 weeks) and after intervention (16 weeks)
Structural brain status (3)	R2*	Baseline (0 weeks) and after intervention (16 weeks)

Collaborators and Investigators

• Sponsor: Maastricht University Medical Center
• Investigators: Principal Investigator: Ronald P. Mensink, Dr, Maastricht University

Study record dates

Study Major Dates

• Study Start (Actual): January 22, 2020
• Primary Completion (Actual): December 1, 2020
• Study Completion (Actual): December 1, 2020

Study Registration Dates

• First Submitted: December 20, 2019
• First Submitted That Met QC Criteria: January 15, 2020
• First Posted (Actual): January 21, 2020

Study Record Updates

• Last Update Posted (Actual): April 19, 2021
• Last Update Submitted That Met QC Criteria: April 14, 2021
• Last Verified: April 1, 2021

More Information

Terms related to this study

• Other Study ID Numbers: METC19-072

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No