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Identification of Predictors for Early Cognitive Decline in Men

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ClinicalTrials.gov Identifier: NCT03290040
Recruitment Status : Recruiting
First Posted : September 21, 2017
Last Update Posted : September 25, 2017
Sponsor:
Collaborators:
University of Copenhagen
Center for Healthy Aging, University of Copenhagen
Information provided by (Responsible Party):
Martin Lauritzen, Rigshospitalet, Denmark

Brief Summary:
The research program explores how aging influences brain function in test-persons from a Danish birth cohort of men born in 1953.

Condition or disease
Healthy Test Persons

Detailed Description:

The research program explores how aging influences brain function in test-persons from a Danish birth cohort of men born in 1953 in the Metropolitan area of Copenhagen.

Test-persons are divided among three groups based on performance in cognitive tests at late midlife compared to young adulthood; 1) Positive expected performance, 2) expected performance and 3) negative expected performance and sampled from a birth cohort of 11.532 men.

Researchers aim to identify factors earlier in life that affect or predict changes in cognitive function, specifically of cognitive decline in order to predict healthy vs unhealthy cognitive aging, including progression to possible dementia. The objective is to be able to predict cognitive decline in aging.

During the four years of data collection approximately 300-400 participants will be included and examined.

The examinations include cognitive test including Cambridge Neuropsychological test automated Battery (CANTAB); sleep, life events and depression questionnaire; blood sample analysis including functional analyses of mitochondria and gen analyses such as genome scanning, SNP analysis, ApoE ε-type; structural and functional changes in the brain measured with magnetic resonance (fMRI) and electroencephalography (EEG) recordings of electrical activity and visual attention.

The results from these studies will hopefully point to new avenues for intervention in order to change the course of brain aging.


Study Type : Observational
Estimated Enrollment : 350 participants
Observational Model: Cohort
Time Perspective: Prospective
Official Title: Identification of Predictors for Early Cognitive Decline: a Longitudinal Cohort Study in Men Born in 1953
Study Start Date : January 2015
Estimated Primary Completion Date : December 2018
Estimated Study Completion Date : February 2030



Primary Outcome Measures :
  1. Gamma band EEG power during evoked potentials correlates to cognitive decline [ Time Frame: Participant is recruited and measured once at the examination day and reexamined every 5 year as long as the project is running and includes the measurement, expected up to 10 years ]
    Visual and auditory evoked potentials are elicited in the brain using flickering visual stimuli and amplitude-modulated tones, respectively. The potentials are recorded through scalp electroencephalography (EEG), using a 64-channel EEG cap. A measure of cognitive decline is approximated using intelligence test scores collected at three distinct times in the lifespan of the subject, as well as other clinical cognitive tests sensitive to aging effects

  2. Alpha band EEG-power during evoked potentials correlates to cognitive decline [ Time Frame: Participant is recruited and measured once at the examination day and reexamined every 5 year as long as the project is running and includes the measurement, expected up to 10 years ]
    Visual evoked potentials are elicited in the brain using flickering visual stimulus. The potentials are recorded through scalp electroencephalography (EEG), using a 64-channel EEG cap. A measure of cognitive decline is approximated using intelligence test scores collected at three distinct times in the lifespan of the subject, as well as other clinical cognitive tests sensitive to aging effects

  3. Examination of how visual attention effects cognitive deterioration. [ Time Frame: Participant is recruited and measured once at the examination day and reexamined every 5 year as long as the project is running and includes the measurement, expected up to 10 years ]
    The accuracy of reporting shown isoluminant letters of the patient is compared to speed of processing (ms), IQ and short term memory function.

  4. Clarification of how processing speed (ms), short term memory and visual perceptive threshold effect cognitive capacity. [ Time Frame: Participant is recruited and measured once at the examination day and reexamined every 5 year as long as the project is running and includes the measurement, expected up to 10 years ]
    Relating brain states to attentional functions by linking visual event-related potentials measured with EEG to specific attentional functions derived from behavioural testing

  5. Changes in mitochondrial respiration as predictor of cognitive impairment [ Time Frame: Participant is recruited and measured once at the examination day and reexamined every 5 year as long as the project is running and includes the measurement, expected up to 10 years ]
  6. Microstructural parameters, derived from diffusion tensor imaging as predictor of cognitive impairment [ Time Frame: Participant is recruited and measured once at the examination day and reexamined every 5 year as long as the project is running and includes the measurement, expected up to 10 years ]
  7. Correlation between basal ganglia volumes and structure and cognitive functions [ Time Frame: Participant is recruited and measured once at the examination day and reexamined every 5 year as long as the project is running and includes the measurement, expected up to 10 years ]
    Cognitive composite scores are based on CANTAB as well as paper and pencil tests. Basal ganglia volumes are based on automatic segmentation procedures. Basal ganglia microstructure and iron content will be estimated using quantitative susceptibility imaging

  8. Correlation between patterns of brain perfusion and patterns of cognitive function [ Time Frame: Participant is recruited and measured once at the examination day and reexamined every 5 year as long as the project is running and includes the measurement, expected up to 10 years ]
    Cognitive composite scores are based on CANTAB as well as paper and pencil tests. Brain perfusion will be measured with arterial spin labeling, and the analysis performed using multivariate techniques

  9. Correlation between Subjective sleep quality and patterns of cognitive function [ Time Frame: Participant is recruited and measured once at the examination day and reexamined every 5 year as long as the project is running and includes the measurement, expected up to 10 years ]
    Cognitive functions are based on CANTAB as well as paper and pencil tests. Sleep quality is measured using the self-report questionnaire Pittsburgh Sleep quality Index (PSQI).

  10. Objective sleep measures: Sleep stages as determined by standard international scoring and quantitated measures using - spectral analysis from sleep EEG in relation to cognitive impairment [ Time Frame: Participant is recruited and measured once at the examination day and reexamined every 5 year as long as the project is running and includes the measurement, expected up to 10 years ]
  11. Effects of demographic, social and health predictors on change in cognitive function from young adulthood to late midlife [ Time Frame: Participant is recruited and measured once at the examination day and reexamined every 5 year as long as the project is running and includes the measurement, expected up to 10 years ]
    Cognitive composite score (based on CANTAB, paper- and pencil tests)

  12. Correlation between daytime sleepiness and patterns of cognitive function [ Time Frame: Participant is recruited and measured once at the examination day and reexamined every 5 year as long as the project is running and includes the measurement, expected up to 10 years ]
    Cognitive functions are based on CANTAB as well as paper and pencil tests. Daytime sleepiness is measured using the Epworh Sleepiness Scale (ESS) questionnaire.


Secondary Outcome Measures :
  1. Gamma band EEG power distribution across the scalp during simultaneous auditory and visual stimulation correlates to cognitive decline [ Time Frame: Participant is recruited and measured once at the examination day and reexamined every 5 year as long as the project is running and includes the measurement, expected up to 10 years ]
    Visual and auditory evoked potentials are elicited in the brain using a paradigm that presents a visual stimulus and an auditory stimulus simultaneously. The potentials are recorded through scalp electroencephalography (EEG), using a 64-channel EEG cap. A measure of cognitive decline is approximated using intelligence test scores collected at three distinct times in the lifespan of the subject

  2. Change of source location of gamma band EEG power of visual evoked potentials correlates to cognitive decline [ Time Frame: Participant is recruited and measured once at the examination day and reexamined every 5 year as long as the project is running and includes the measurement, expected up to 10 years ]
    Visual evoked potentials are elicited in the brain using flickering visual stimulus. The potentials are recorded through scalp electroencephalography (EEG), using a 64-channel EEG cap. A measure of cognitive decline is approximated using intelligence test scores collected at three distinct times in the lifespan of the subject, as well as other clinical cognitive tests sensitive to aging effects

  3. The investigators would like to describe how visual attention correlates with the background EEG recorded before the examination. [ Time Frame: Participant is recruited and measured once at the examination day and reexamined every 5 year as long as the project is running and includes the measurement, expected up to 10 years ]
    Linking functional effects of prestimulus alpha power measured by EEG to perception accuracy

  4. Change in levels of reactive oxygen species in PBMCs quantified by flow cytometry after application of dedicated fluorophores as predictor of cognitive impairment [ Time Frame: Participant is recruited and measured once at the examination day and reexamined every 5 year as long as the project is running and includes the measurement, expected up to 10 years ]
  5. Change in levels of mitochondrial bioenergetics in PBMCs using the Seahorse XF24 extracellular flux analyser as predictor of cognitive impairment [ Time Frame: Participant is recruited and measured once at the examination day and reexamined every 5 year as long as the project is running and includes the measurement, expected up to 10 years ]
  6. Change of levels of whole cell dNTP levels in PBMCs using polymerase extension assay and by quantification of tritiated nucleotides by scintillation counting as predictor of cognitive impairment [ Time Frame: Participant is recruited and measured once at the examination day and reexamined every 5 year as long as the project is running and includes the measurement, expected up to 10 years ]
  7. Change of mutation frequency of mitochondrial DNA using deep sequencing as predictor of cognitive impairment [ Time Frame: Participant is recruited and measured once at the examination day and reexamined every 5 year as long as the project is running and includes the measurement, expected up to 10 years ]
  8. Change of mtDNA copy number by qPCR as predictor of cognitive impairment [ Time Frame: Participant is recruited and measured once at the examination day and reexamined every 5 year as long as the project is running and includes the measurement, expected up to 10 years ]
  9. Correlation between regional cortical thickness and cognitive parameters [ Time Frame: Participant is recruited and measured once at the examination day and reexamined every 5 year as long as the project is running and includes the measurement, expected up to 10 years ]
    Cognitive composite scores are based on CANTAB as well as paper and pencil tests. Cortical thickness will be analysed using FreeSurfer or similar software, and the analysis performed using multivariate techniques

  10. Correlation between regional cortical surface and cognitive parameters [ Time Frame: Participant is recruited and measured once at the examination day and reexamined every 5 year as long as the project is running and includes the measurement, expected up to 10 years ]
    Cognitive composite scores are based on CANTAB as well as paper and pencil tests. Cortical surface will be analysed using FreeSurfer or similar software, and the analysis performed using multivariate techniques

  11. Correlation between macrostructural parameters and candidate genes [ Time Frame: Participant is recruited and measured once at the examination day and reexamined every 5 year as long as the project is running and includes the measurement, expected up to 10 years ]
    Macrostructural parameters will be derived from segmentation of T1-weighted images. The statistical analysis will consider macrostructural parameters as a possible mediator of common genetic variants upon cognition. Candidate genes will be selected due to their relation to 1) cardiovascular function and disease 2) oxidative stress, longevity and ageing and 3) memory and intelligence.

  12. Correlation between microstructural parameters and candidate genes [ Time Frame: Participant is recruited and measured once at the examination day and reexamined every 5 year as long as the project is running and includes the measurement, expected up to 10 years ]
    Microstructural parameters will be derived from diffusion tensor imaging. The statistical analysis will consider microstructural parameters as a possible mediator of common genetic variants upon cognition. Candidate genes will be selected due to their relation to 1) cardiovascular function and disease 2) oxidative stress, longevity and ageing and 3) memory and intelligence.

  13. Correlation between macrostructural parameters and cognition [ Time Frame: Participant is recruited and measured once at the examination day and reexamined every 5 year as long as the project is running and includes the measurement, expected up to 10 years ]
    Macrostructural parameters will be derived from segmentation of T1-weighted images. Cognitive composite scores are based on CANTAB as well as paper and pencil test.

  14. Correlation between microstructural parameters and cognition [ Time Frame: Participant is recruited and measured once at the examination day and reexamined every 5 year as long as the project is running and includes the measurement, expected up to 10 years ]
    Microstructural parameters will be derived from diffusion tensor imaging. Cognitive composite scores are based on CANTAB as well as paper and pencil test.

  15. Correlation between cognition and candidate genes [ Time Frame: Participant is recruited and measured once at the examination day and reexamined every 5 year as long as the project is running and includes the measurement, expected up to 10 years ]
    Cognitive composite scores are based on CANTAB as well as paper and pencil test.Candidate genes will be selected due to their relation to 1) cardiovascular function and disease 2) oxidative stress, longevity and ageing and 3) memory and intelligence.

  16. Correlation between sleep stages and microstructural parameters. [ Time Frame: Participant is recruited and measured once at the examination day and reexamined every 5 year as long as the project is running and includes the measurement, expected up to 10 years ]
    Sleep stages will be determined by standard international scoring and quantitated measures using spectral analysis from sleep EEG. Microstructures will be measured with MRI.

  17. Correlation between sleep stages and regional volumes. [ Time Frame: Participant is recruited and measured once at the examination day and reexamined every 5 year as long as the project is running and includes the measurement, expected up to 10 years ]
    Sleep stages will be determined by standard international scoring and quantitated measures using spectral analysis from sleep EEG. Regional volumes will be measured with MRI.

  18. Autonomic activity as measured by electrocardiography determined from the polysomnography during wakefulness and sleep in relation to cognitive impairment [ Time Frame: Participant is recruited and measured once at the examination day and reexamined every 5 year as long as the project is running and includes the measurement, expected up to 10 years ]
  19. Presence of REM Sleep muscle activity (REM sleep without atonia (RSWA), REM Behavior disorder(RBD)) in relation to cognitive impairment [ Time Frame: Participant is recruited and measured once at the examination day and reexamined every 5 year as long as the project is running and includes the measurement, expected up to 10 years ]
  20. Cognitive correlates of cognitive change [ Time Frame: Participant is recruited and measured once at the examination day and reexamined every 5 year as long as the project is running and includes the measurement, expected up to 10 years ]
    Cognitive composite score (based on CANTAB, paper- and pencil tests)


Biospecimen Retention:   Samples With DNA
Blood samples with DNA


Information from the National Library of Medicine

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Ages Eligible for Study:   60 Years and older   (Adult, Senior)
Sexes Eligible for Study:   Male
Accepts Healthy Volunteers:   No
Sampling Method:   Non-Probability Sample
Study Population

Danish birth cohort of 11.532 men born in 1953 in the Metropolitan area of Copenhagen.

Only men who have participated in the Copenhagen Aging and Midlife Biobank project are considered.

Criteria

Inclusion Criteria:

  • Participants who have participated in the Metropolit study and in the Copenhagen Aging and Midlife Biobank project
  • Participants who have been informed about the project and who have signed the informed consent form

Exclusion Criteria:

  • Persons who have been asked to participate in the past and have rejected
  • Reduced ability to understand project information
  • Reduced ability to complete the examinations
  • Abuse of alcohol, psychedelic drugs or habit-forming drugs
  • Certain neurological disorders
  • Certain neurological, mental or psychiatric diagnoses
  • Certain depressive diseases
  • Former traumatic brain injury
  • Contraindication for MR scanning
  • Pathological MR result
  • Persons that do not like to be informed about a possible pathological result

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03290040


Contacts
Contact: Lene Rask, PhD +45 38634009 lene.rask.01@regionh.dk
Contact: Martin J Lauritzen, Prof +45 38 63 39 33 martin.johannes.lauritzen@regionh.dk

Locations
Denmark
Dept. of Clinical Neurophysiology, Department of Clinical Biochemistry and Department of Clinical Physiology, Nuclear Medicine and PET, Rigshospitalet - Glostrup Recruiting
Glostrup, Denmark, 2600
Contact: Lene Rask, PhD    +45 38634009    lene.rask.01@regionh.dk   
Contact: Martin J Lauritzen, Prof    +45 38 63 39 33    martin.johannes.lauritzen@regionh.dk   
Sponsors and Collaborators
Rigshospitalet, Denmark
University of Copenhagen
Center for Healthy Aging, University of Copenhagen
Investigators
Principal Investigator: Martin J Lauritzen, Prof Dept. of Clinical Neurophysiology, Rigshospitalet - Glostrup
Principal Investigator: Martin J Lauritzen, Prof Dept. of Clinical Neurophysiology, Rigshospitalet - Glostrup, Neuronal Signalling Lab, Center for Neuroscience, University of Copenhagen and Center for Healthy aging, University of Copenhagen

Responsible Party: Martin Lauritzen, Professor, Consulting, Rigshospitalet, Denmark
ClinicalTrials.gov Identifier: NCT03290040     History of Changes
Other Study ID Numbers: H-1-2014-032
First Posted: September 21, 2017    Key Record Dates
Last Update Posted: September 25, 2017
Last Verified: September 2017

Additional relevant MeSH terms:
Cognitive Dysfunction
Cognition Disorders
Neurocognitive Disorders
Mental Disorders