Clinical trial NCT03290040: Identification of Predictors for Early Cognitive Decline in Men
Official title: Identification of Predictors for Early Cognitive Decline: a Longitudinal Cohort Study in Men Born in 1953
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Healthy Test Persons
Mild Cognitive Impairment
Alzheimer Disease
Lead sponsor: Rigshospitalet, Denmark
Sponsor class: OTHER
Collaborators: name: University of Copenhagen
name: Herlev Hospital
First posted: 2017-09-21
Enrollment: 564
Sex: MALE
Minimum age (years): 60
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
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.

Persons from the Memory Clinic at Herlev Hospital will be included in the period 2020-2021. These individuals are diagnosed with either MCI or AD.

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

Detailed description: The research program explores how ageing influences brain function in healthy test-persons from a Danish birth cohort of men born in 1953 in the Metropolitan area of Copenhagen. These test-persons are divided into two groups based on performance in cognitive tests at late midlife compared to young adulthood; Positive expected performance and negative expected performance and sampled from a birth cohort of 11.532 men.

Additionally, persons diagnosed with either MCI or AD will be included from the Memory Clinic at Herlev Hospital.

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

During the years of data collection, approximately 550 participants will be included and examined.

The examinations include:

* Cognitive test including Cambridge Neuropsychological test automated Battery (CANTAB);
* Sleep
* Life events
* Depression questionnaire
* Blood sample analysis including functional analyses of mitochondria and gene analyses such as genome scanning, SNP analysis
* ApoE ε-type
* Structural and functional changes in the brain measured with magnetic resonance (fMRI)
* Electroencephalography (EEG) recordings of electrical activity and visual attention
* PET-scan (Amyloid and FDG)

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

Eligibility criteria: Inclusion Criteria:

* Participants who have participated in the Metropolit study and 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

Primary outcomes:
measure: Gamma band EEG power during evoked potentials correlates to cognitive decline
timeFrame: 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
measure: Alpha band EEG-power during evoked potentials correlates to cognitive decline
timeFrame: 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
measure: Examination of how visual attention effects cognitive deterioration.
timeFrame: 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
measure: Clarification of how processing speed (ms), short term memory and visual perceptive threshold effect cognitive capacity.
timeFrame: 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
measure: Changes in mitochondrial respiration as predictor of cognitive impairment
timeFrame: 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
measure: Microstructural parameters, derived from diffusion tensor imaging as predictor of cognitive impairment
timeFrame: 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
measure: Correlation between basal ganglia volumes and structure and cognitive functions
timeFrame: 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
measure: Correlation between patterns of brain perfusion and patterns of cognitive function
timeFrame: 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
measure: Correlation between Subjective sleep quality and patterns of cognitive function
timeFrame: 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
measure: 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
timeFrame: 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
measure: Effects of demographic, social and health predictors on change in cognitive function from young adulthood to late midlife
timeFrame: 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
measure: Correlation between daytime sleepiness and patterns of cognitive function
timeFrame: 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
measure: FDG - PET
timeFrame: This examination will be performed in 2020-2021.
measure: PIB - PET
timeFrame: This examination will be performed in 2020-2021.
Secondary outcomes:
measure: Gamma band EEG power distribution across the scalp during simultaneous auditory and visual stimulation correlates to cognitive decline
timeFrame: 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
measure: Change of source location of gamma band EEG power of visual evoked potentials correlates to cognitive decline
timeFrame: 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
measure: The investigators would like to describe how visual attention correlates with the background EEG recorded before the examination.
timeFrame: 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
measure: Change in levels of reactive oxygen species in PBMCs quantified by flow cytometry after application of dedicated fluorophores as predictor of cognitive impairment
timeFrame: 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
measure: Change in levels of mitochondrial bioenergetics in PBMCs using the Seahorse XF24 extracellular flux analyser as predictor of cognitive impairment
timeFrame: 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
measure: 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
timeFrame: 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
measure: Change of mutation frequency of mitochondrial DNA using deep sequencing as predictor of cognitive impairment
timeFrame: 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
measure: Change of mtDNA copy number by qPCR as predictor of cognitive impairment
timeFrame: 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
measure: Correlation between regional cortical thickness and cognitive parameters
timeFrame: 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
measure: Correlation between regional cortical surface and cognitive parameters
timeFrame: 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
measure: Correlation between macrostructural parameters and candidate genes
timeFrame: 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
measure: Correlation between microstructural parameters and candidate genes
timeFrame: 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
measure: Correlation between macrostructural parameters and cognition
timeFrame: 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
measure: Correlation between microstructural parameters and cognition
timeFrame: 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
measure: Correlation between cognition and candidate genes
timeFrame: 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
measure: Correlation between sleep stages and microstructural parameters.
timeFrame: 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
measure: Correlation between sleep stages and regional volumes.
timeFrame: 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
measure: Autonomic activity as measured by electrocardiography determined from the polysomnography during wakefulness and sleep in relation to cognitive impairment
timeFrame: 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
measure: Presence of REM Sleep muscle activity (REM sleep without atonia (RSWA), REM Behavior disorder(RBD)) in relation to cognitive impairment
timeFrame: 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
measure: Cognitive correlates of cognitive change
timeFrame: 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
Other outcomes:
Locations:
city: Glostrup
country: Denmark
facility: Dept. of Clinical Neurophysiology, Department of Clinical Biochemistry and Department of Clinical Physiology, Nuclear Medicine and PET, Rigshospitalet - Glostrup
Study officials:
affiliation: Dept. of Clinical Neurophysiology, Rigshospitalet - Glostrup
name: Martin J Lauritzen, Prof
role: PRINCIPAL_INVESTIGATOR
affiliation: Dept. of Clinical Neurophysiology, Rigshospitalet - Glostrup, Neuronal Signalling Lab, Center for Neuroscience, and Center for Healthy aging, University of Copenhagen
name: Martin J Lauritzen, Prof
role: PRINCIPAL_INVESTIGATOR
References: