A Combined Multidomain Intervention to Prevent Cognitive Decline Associated With Cardiovascular Risk Factors.

Aging Clinical Trial

— ACTIONcR  

Official title:

Impacts of Aerobic, Resistance and Cognitive Training Interventions on Neurocognitive Functions in Older Adults With Cardiovascular Risk Factors.

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04962061
• Other study ID #: 2019-2545
• Status: Recruiting
• Phase: N/A
• Start date: September 1, 2021
• Est. completion date: January 30, 2025

Study information

• Verified date: July 2023
• Source: Montreal Heart Institute
• Contact: Louis Bherer, PhD
• Phone: 514-374-1480
• Email: louis.bherer[@]umontreal.ca
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The ACTIONcardioRisk trial is designed to investigate the effect of aerobic and progressive resistance training exercises combined with cognitive training, on neurocognitive functioning of sedentary older adults with and without cardiovascular risk factors.

Description:

The proportion of older adults is on the rise in Canada, with the fastest growth recorded among those seventy years of age or older. The prevalence of cardiovascular risk factors (CVRF) such as diabetes, hypertension, and high cholesterol increases drastically with age. Individuals with CVRF often show impaired cognition, such as attention and memory deficits. In healthy older adults, exercise training and cognitive stimulation can help enhance cognitive performances. More precisely, combined intervention, including physical and cognitive training, has shown beneficial effects on cognition in older adults without cognitive impairment and with mild cognitive impairment. However, the effect of such programs on cognition in individuals with CVRF is not well documented. This project compares the effect of a physical exercise program, including aerobic and resistance training, alone or combined with cognitive training on cognitive performances and brain imaging outcomes in individuals with CVRF and healthy controls.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 159
• Est. completion date: January 30, 2025
• Est. primary completion date: January 30, 2025
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 60 Years and older

Eligibility

Inclusion Criteria:

• Adult aged 60 and older,
• Normal or corrected vision and normal hearing for their age range,
• No cognitive impairment (Mini-Mental State Examination - MMSE = 25),
• Inactive (< 150 min of physical activity per week).

Exclusion Criteria:

• MMSE = 24 or diagnosis of dementia,
• Uncontrolled psychological / psychiatric condition within the past 6 months,
• Neurological disease,
• Severe exercise intolerance,
• Respiratory disease (e.g., asthma, COPD),
• Excessive alcohol consumption (> 15 drinks/week),
• Documented cerebral, peripheral or coronary atherosclerotic disease,
• Chronic systolic or diastolic heart failure,
• Symptomatic aortic stenosis,
• Atrial fibrillation,
• Automatic implantable defibrillator or permanent pacemaker,
• Malignant exertional arrhythmias,
• Non-cardiopulmonary limitation to exercise (e.g., arthritis).

Related Conditions & MeSH terms

• Aging
• Cardiovascular Risk Factor

Intervention

Other:
• Cognitive Training
Participants will be encouraged to perform sessions of cognitive training 3 times per week (30 minutes/session). Two of these sessions will involve computer- or tablet-based attentional control training targeting dual-tasking, updating and working memory, as well as inhibition and switching. Difficulty of cognitive training will be tailored to participants' performances. The remaining session will consist of memory training. Participants will be instructed mnemotechnic, as well as be taught about memory in aging in general.
• Aerobic and resistance exercises
Participants will follow a periodized exercise training program with thrice-weekly 60 minutes trainings. The sessions will start with a 5-10mins warm-up, followed by aerobic and resistance trainings, and ends with a 5-10mins cool-down and stretching period. Intensity of aerobic sessions will be monitored with heart rate chest strap and should match with the moderate to vigorous intensity zone as defined by the ACSM (65% of Heart Rate maximum or more and a Perceived Exertion higher than 12 on the 6 to 20 Borg scale). Exercise intensity and duration will be gradually increased during the program. After aerobic training, a 15-20mins resistance training will be performed with a gradual progression of higher intensities and/or numbers of sets. The one maximal repetition (1RM) will be assessed for each RT movements at baseline, during (each 3 months) and at the end of the program. RT intensities will go from 40 to 70% of 1RM, with 8 to 10 forms of exercise involving majors muscle groups.
• Stretching and Toning
Participants in the active control condition will take part in three 60 minutes stretching and toning sessions per week. Each session will start with a five-minutes warm-up, followed by fifteen min of body stretching exercises mainly in a seated position and finish with a five-minutes cool down. Participants will engage in four muscle-toning exercises (light intensity) using dumbbells or resistance bands, two exercises designed to improve balance, one yoga sequence, and one exercise of their choice. Intensity of stretching and toning sessions will be monitored with heart rate chest strap and should not exceed the light intensity zone as defined by the ACSM (64% of Heart Rate maximum or less and a Perceived Exertion lower than 11 on the 6 to 20 Borg scale).

Locations

Country	Name	City	State
Canada	Preventive medicine and physical activity centre (centre EPIC), Montreal Heart Institute	Montreal	Quebec

Sponsors (3)

Lead Sponsor	Collaborator
Louis Bherer	Canadian Institutes of Health Research (CIHR), The Montreal Health Innovations Coordinating Center (MHICC)

Country where clinical trial is conducted

Canada, 

References & Publications (23)

Arntzen KA, Schirmer H, Wilsgaard T, Mathiesen EB. Impact of cardiovascular risk factors on cognitive function: the Tromso study. Eur J Neurol. 2011 May;18(5):737-43. doi: 10.1111/j.1468-1331.2010.03263.x. Epub 2010 Dec 8. — View Citation

Baker LD, Frank LL, Foster-Schubert K, Green PS, Wilkinson CW, McTiernan A, Cholerton BA, Plymate SR, Fishel MA, Watson GS, Duncan GE, Mehta PD, Craft S. Aerobic exercise improves cognition for older adults with glucose intolerance, a risk factor for Alzheimer's disease. J Alzheimers Dis. 2010;22(2):569-79. doi: 10.3233/JAD-2010-100768. — View Citation

Bherer L, Kramer AF, Peterson MS, Colcombe S, Erickson K, Becic E. Training effects on dual-task performance: are there age-related differences in plasticity of attentional control? Psychol Aging. 2005 Dec;20(4):695-709. doi: 10.1037/0882-7974.20.4.695. — View Citation

Colcombe S, Kramer AF. Fitness effects on the cognitive function of older adults: a meta-analytic study. Psychol Sci. 2003 Mar;14(2):125-30. doi: 10.1111/1467-9280.t01-1-01430. — View Citation

DeRight J, Jorgensen RS, Cabral MJ. Composite cardiovascular risk scores and neuropsychological functioning: a meta-analytic review. Ann Behav Med. 2015 Jun;49(3):344-57. doi: 10.1007/s12160-014-9681-0. — View Citation

Dregan A, Stewart R, Gulliford MC. Cardiovascular risk factors and cognitive decline in adults aged 50 and over: a population-based cohort study. Age Ageing. 2013 May;42(3):338-45. doi: 10.1093/ageing/afs166. Epub 2012 Nov 25. — View Citation

Erickson KI, Colcombe SJ, Wadhwa R, Bherer L, Peterson MS, Scalf PE, Kim JS, Alvarado M, Kramer AF. Training-induced functional activation changes in dual-task processing: an FMRI study. Cereb Cortex. 2007 Jan;17(1):192-204. doi: 10.1093/cercor/bhj137. Epub 2006 Feb 8. — View Citation

Eskelinen MH, Ngandu T, Helkala EL, Tuomilehto J, Nissinen A, Soininen H, Kivipelto M. Fat intake at midlife and cognitive impairment later in life: a population-based CAIDE study. Int J Geriatr Psychiatry. 2008 Jul;23(7):741-7. doi: 10.1002/gps.1969. — View Citation

Friedman JI, Tang CY, de Haas HJ, Changchien L, Goliasch G, Dabas P, Wang V, Fayad ZA, Fuster V, Narula J. Brain imaging changes associated with risk factors for cardiovascular and cerebrovascular disease in asymptomatic patients. JACC Cardiovasc Imaging. 2014 Oct;7(10):1039-53. doi: 10.1016/j.jcmg.2014.06.014. — View Citation

Hodyl NA, Schneider L, Vallence AM, Clow A, Ridding MC, Pitcher JB. The cortisol awakening response is associated with performance of a serial sequence reaction time task. Int J Psychophysiol. 2016 Feb;100:12-8. doi: 10.1016/j.ijpsycho.2015.12.007. Epub 2015 Dec 22. — View Citation

Jennings JR, Muldoon MF, Ryan C, Price JC, Greer P, Sutton-Tyrrell K, van der Veen FM, Meltzer CC. Reduced cerebral blood flow response and compensation among patients with untreated hypertension. Neurology. 2005 Apr 26;64(8):1358-65. doi: 10.1212/01.WNL.0000158283.28251.3C. — View Citation

Karssemeijer EGA, Aaronson JA, Bossers WJ, Smits T, Olde Rikkert MGM, Kessels RPC. Positive effects of combined cognitive and physical exercise training on cognitive function in older adults with mild cognitive impairment or dementia: A meta-analysis. Ageing Res Rev. 2017 Nov;40:75-83. doi: 10.1016/j.arr.2017.09.003. Epub 2017 Sep 12. — View Citation

Kobe T, Witte AV, Schnelle A, Lesemann A, Fabian S, Tesky VA, Pantel J, Floel A. Combined omega-3 fatty acids, aerobic exercise and cognitive stimulation prevents decline in gray matter volume of the frontal, parietal and cingulate cortex in patients with mild cognitive impairment. Neuroimage. 2016 May 1;131:226-38. doi: 10.1016/j.neuroimage.2015.09.050. Epub 2015 Oct 1. — View Citation

Launer LJ, Lewis CE, Schreiner PJ, Sidney S, Battapady H, Jacobs DR, Lim KO, D'Esposito M, Zhang Q, Reis J, Davatzikos C, Bryan RN. Vascular factors and multiple measures of early brain health: CARDIA brain MRI study. PLoS One. 2015 Mar 26;10(3):e0122138. doi: 10.1371/journal.pone.0122138. eCollection 2015. — View Citation

Lupien SJ, Maheu F, Tu M, Fiocco A, Schramek TE. The effects of stress and stress hormones on human cognition: Implications for the field of brain and cognition. Brain Cogn. 2007 Dec;65(3):209-37. doi: 10.1016/j.bandc.2007.02.007. Epub 2007 Apr 26. — View Citation

Lussier M, Gagnon C, Bherer L. An investigation of response and stimulus modality transfer effects after dual-task training in younger and older. Front Hum Neurosci. 2012 May 18;6:129. doi: 10.3389/fnhum.2012.00129. eCollection 2012. — View Citation

Ngandu T, Lehtisalo J, Solomon A, Levalahti E, Ahtiluoto S, Antikainen R, Backman L, Hanninen T, Jula A, Laatikainen T, Lindstrom J, Mangialasche F, Paajanen T, Pajala S, Peltonen M, Rauramaa R, Stigsdotter-Neely A, Strandberg T, Tuomilehto J, Soininen H, Kivipelto M. A 2 year multidomain intervention of diet, exercise, cognitive training, and vascular risk monitoring versus control to prevent cognitive decline in at-risk elderly people (FINGER): a randomised controlled trial. Lancet. 2015 Jun 6;385(9984):2255-63. doi: 10.1016/S0140-6736(15)60461-5. Epub 2015 Mar 12. — View Citation

Stampfer MJ, Hu FB, Manson JE, Rimm EB, Willett WC. Primary prevention of coronary heart disease in women through diet and lifestyle. N Engl J Med. 2000 Jul 6;343(1):16-22. doi: 10.1056/NEJM200007063430103. — View Citation

van den Berg E, Kloppenborg RP, Kessels RP, Kappelle LJ, Biessels GJ. Type 2 diabetes mellitus, hypertension, dyslipidemia and obesity: A systematic comparison of their impact on cognition. Biochim Biophys Acta. 2009 May;1792(5):470-81. doi: 10.1016/j.bbadis.2008.09.004. Epub 2008 Sep 23. — View Citation

Vianna LC, Deo SH, Jensen AK, Holwerda SW, Zimmerman MC, Fadel PJ. Impaired dynamic cerebral autoregulation at rest and during isometric exercise in type 2 diabetes patients. Am J Physiol Heart Circ Physiol. 2015 Apr 1;308(7):H681-7. doi: 10.1152/ajpheart.00343.2014. Epub 2015 Jan 16. — View Citation

Wang R, Fratiglioni L, Laveskog A, Kalpouzos G, Ehrenkrona CH, Zhang Y, Bronge L, Wahlund LO, Backman L, Qiu C. Do cardiovascular risk factors explain the link between white matter hyperintensities and brain volumes in old age? A population-based study. Eur J Neurol. 2014 Aug;21(8):1076-1082. doi: 10.1111/ene.12319. Epub 2013 Dec 7. — View Citation

Yamamoto N, Yamanaka G, Takasugi E, Ishikawa M, Yamanaka T, Murakami S, Hanafusa T, Matsubayashi K, Otsuka K. Lifestyle intervention reversed cognitive function in aged people with diabetes mellitus: two-year follow up. Diabetes Res Clin Pract. 2009 Sep;85(3):343-6. doi: 10.1016/j.diabres.2009.05.014. Epub 2009 Jun 10. — View Citation

Zhu X, Yin S, Lang M, He R, Li J. The more the better? A meta-analysis on effects of combined cognitive and physical intervention on cognition in healthy older adults. Ageing Res Rev. 2016 Nov;31:67-79. doi: 10.1016/j.arr.2016.07.003. Epub 2016 Jul 14. — View Citation

* Note: There are 23 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Change in cardiorespiratory fitness	Maximum incremental cardiopulmonary exercise test (VO2 max (ml.kg.min)).	Baseline and post-intervention at 12 months.
Other	Change in peripheral endothelial function	Fow-mediated dilation of the brachial artery (%).	Baseline and post-intervention at 12 months.
Other	Change in central artery stiffness	Carotid femoral pulse-wave velocity (m/s).	Baseline and post-intervention at 12 months.
Other	Change in walking speed	Timed 10-meter walking test (cm/s).	Baseline and post-intervention at 12 months.
Other	Change in functional mobility	Timed Time up and Go test (s).	Baseline and post-intervention at 12 months.
Other	Change in Balance performance	Timed one-leg standing test (s).	Baseline and post-intervention at 12 months.
Other	Change in lower limb muscles strength	Timed Sit-to-Stand test (s)	Baseline and post-intervention at 12 months.
Other	Change in upper limb muscle strength	Grip strength test score (kg).	Baseline and post-intervention at 12 months.
Other	Change in total cholesterol	Total cholesterol levels (mmol/L)	Baseline and post-intervention at 12 months.
Other	Change in cholesterol-HDL	Cholesterol-HDL levels (mmol/L)	Baseline and post-intervention at 12 months.
Other	Change in cholesterol-LDL calculated	Cholesterol-LDL calculated levels (mmol/L)	Baseline and post-intervention at 12 months.
Other	Change in cholesterol non-HDL	Cholesterol non-HDL levels (mmol/L)	Baseline and post-intervention at 12 months.
Other	Change in triglycerides	Triglycerides levels (mmol/L)	Baseline and post-intervention at 12 months.
Other	Change in glucose	Glucose levels (mmol/L)	Baseline and post-intervention at 12 months.
Other	Change in glycated hemoglobin (HbA1c)	Glycated hemoglobin (HbA1c) (%)	Baseline and post-intervention at 12 months.
Other	Change in insulin	Insulin levels (pmol/L)	Baseline and post-intervention at 12 months.
Other	Change in creatinine	Creatinine levels (mg/dL)	Baseline and post-intervention at 12 months.
Other	Change in sodium	Sodium levels (mmol/L)	Baseline and post-intervention at 12 months.
Other	Change in chloride	Chloride levels (mmol/L)	Baseline and post-intervention at 12 months.
Other	Change in potassium	Potassium levels (mmol/L)	Baseline and post-intervention at 12 months.
Other	Change in high-sensitive C-reactive protein (hsCRP)	High-sensitive C-reactive protein (hsCRP) levels (mg/L)	Baseline and post-intervention at 12 months.
Other	Change in apolipoprotein B (ApoB)	Apolipoprotein B (ApoB) levels (g/L)	Baseline and post-intervention at 12 months.
Other	Change of neurotrophic biomarkers	Brain-derived neurotrophic factor (BDNF) plasma concentration (pg/mL).	Baseline and post-intervention at 12 months.
Other	Change in transcriptomics	Transcriptome analysis to assess the impact of the intervention on any changes in the activity of different cellular processes.	Baseline and post-intervention at 12 months.
Other	Change in gut microbiome	DNA extraction from fecal samples. The fecal samples will be collected from the participants who are also performing MRI.	Baseline and post-intervention at 12 months
Other	Change in chronic stress levels	Cortisol levels from saliva samples (nmol/L). The saliva samples will be collected from the participants who are also performing MRI.	Baseline and post-intervention at 12 months.
Other	Change in perceived stress	Perceived Stress Scale questionnaire (Score ranges from 0-4, with 0 no stress,1 mild stress, 3 moderate stress and 4 severe).	Baseline and post-intervention at 12 months.
Other	Change in anxiety	State-Trait Anxiety Inventory questionnaire (Score ranges from 20-80, with a higher score indicating higher anxiety).	Baseline and post-intervention at 12 months.
Other	Change in depressive symptoms	Geriatric Depression Scale questionnaire (Score ranges from 0-30, with a higher score indicating larger depressive symptomatology).	Baseline and post-intervention at 12 months.
Other	Change in health related quality-of-life	12-Item Short Form Health Survey (a completer).	Baseline and post-intervention at 12 months.
Other	Change in sleep quality	Pittsburg Sleep Quality Index questionnaire (Score ranges from 0-21, with a higher score indicating worse sleep quality).	Baseline and post-intervention at 12 months.
Other	Change in Dietary patterns	Short Diet Questionnaire (Score ranges from 15-45 points, with a score between 15-29 categorised as unhealthy, 30-37 as somewhat unhealthy, and 38 or more as a healthy diet).	Baseline and post-intervention at 12 months.
Other	Change in social and community activities involvement	Social and community involvement questionnaire (Score ranges from 0-200, with a higher score indicating more social and community involvement).	Baseline and post-intervention at 12 months.
Other	Change in self-reported physical activity	Physical Activity Scale for the Elderly questionnaire (Score ranges from 0-400, with a higher score indicating better level of physical activity).	Baseline
Other	Self-reported masculinity and femininity trait	Short Form Bem Sex-Role Inventory questionnaire (30 items questionnaire with 10 items assessing the femininity traits, 10 items assessing the masculinity traits, and 10 items neutral, not scored. Two scores are calculated for femininity and masculinity, respectively, and range from 10-70, whit a higher score indicating a higher femininity or masculinity trait).	Baseline
Other	Genetic biomarkers	Genotyping array to generate high quality genome-wide genotyping data that include the APOE and BDNF genes.	Baseline
Other	Cognitive Reserve	Rami and colleagues' cognitive reserve questionnaire (Scale ranges from 0-26, with a higher score indicating a greater cognitive reserve).	Baseline
Other	Baseline level of physical activity	Quantification of physical activity using an accelerometry recording of 7 days (minutes of moderate to vigorous activity).	Baseline
Primary	Change in general cognitive functioning	Montreal Cognitive Assessment (0-30 score, with a higher score indicating a better cognitive functioning).	Baseline and post-intervention at 12 months.
Primary	Change in processing speed	Validated remote version of neuropsychological tests and iPad tests (Composite Z-score).	Baseline and post-intervention at 12 months.
Primary	Change in executive functions	Validated remote version of neuropsychological tests and iPad tests (Composite Z-score).	Baseline and post-intervention at 12 months.
Primary	Change in episodic memory	Validated remote version of neuropsychological tests and iPad tests (Composite Z-score).	Baseline and post-intervention at 12 months.
Secondary	Change in cerebral autoregulation - frontal cortical region	Variations of prefrontal cortical oxygen saturation (rSO2, [HbO]/([HbO]+[HbR])) will be measured by Near Infrared Spectroscopy (NIRS), as a surrogate of cortical blood flow. Variations of continuous peripheral blood pressure (mm Hg) will be simultaneously measured by plethysmography at the finger. Autoregulation indices (unitless) will be derived from the correlation between variations of oxygen saturation measures and variations of peripheral blood pressure.	Baseline and post-intervention at 12 months.
Secondary	Change in cerebral autoregulation - middle cerebral arteries	Variations of cerebral blood flow velocity (cm/s) at the level of the middle cerebral artery will be measured by Transcranial Doppler (TCD). Variations of continuous peripheral blood pressure (mm Hg) will be simultaneously measured by plethysmography at the finger. Autoregulation indices (unitless) will be derived from the correlation between variations of cerebral blood flow measures and variations of peripheral blood pressure.	Baseline and post-intervention at 12 months.
Secondary	Change in cerebral vasoreactivity - whole brain	Cerebral VasoReactivity (CVR, % change per mm Hg of PaCO2) will be measured by Arterial Spin Labeling MRI in two third of the study participants who do not present contra-indication for imaging studies.	Baseline and post-intervention at 12 months.
Secondary	Change in cerebral vasoreactivity - prefrontal cortex	Cerebral VasoReactivity (CVR, % change per mm Hg of PaCO2) will be measured using NIRS in the prefrontal region.	Baseline and post-intervention at 12 months.
Secondary	Change in cerebral vasoreactivity - middle cerebral arteries	Cerebral VasoReactivity (CVR, % change per mm Hg of PaCO2) will be measured using TCD in the middle cerebral arteries	Baseline and post-intervention at 12 months.
Secondary	Change in cerebral pulsatility - cortical frontal region	Pulsatility will be measured as the normalized difference of relative near-infrared light intensity changes between systole and diastole, using NIRS in the prefrontal cortical region.	Baseline and post-intervention at 12 months.
Secondary	Change in cerebral pulsatility - middle cerebral arteries	Pulsatility will be measured as the normalized difference of relative blood flow velocities between systole and diastole, using TCD in the middle cerebral arteries.	Baseline and post-intervention at 12 months.
Secondary	Change in cerebral activity	Significant changes in brain activity evoked by a Stroop task relative to baseline will be assessed by t-statistics maps, computed from variations of [HbO] and [HbR] measured by NIRS at the prefrontal cortex.	Baseline and post-intervention at 12 months.
Secondary	Change in brain structure	Multimodal structural MRI will be performed in two third of the study participants who do not present contra-indication for imaging studies, to measure regional cerebral volumes, as well as volume of angiopathic markers (eg lacunes, microbleeds, white matter hyperintensities), in cm3.	Baseline and post-intervention at 12 months.