Community-based Cohort of Functional Decline in Subjective Cognitive Complaint Elderly

February 10, 2020 updated by: Geroscience Center for Brain Health and Metabolism (Gero)

GERO Cohort Protocol, Chile, 2017 - 2019: Community-based Cohort of Functional Decline in Subjective Cognitive Complaint Elderly

Background With the global population aging and life expectancy increasing, dementia has turned a priority in the health care system. In Chile, dementia is one of the most important causes of disability in elderly, corresponding nearly to 40% of cases, and the most rapidly growing cause of death in the last twenty years. Cognitive complaints are considered a marker able to predict cognitive and functional decline, incident mild cognitive impairment (MCI), and incident dementia. The Gero cohort is the Chilean core clinical project of the Gerocenter on Brain Health and Metabolism (GERO), whose aim is to establish the capacity in Chile to foster cutting edge and multidisciplinary research on aging.

Objective This study has two main objectives. First, i) to analyze the rate of functional decline and progression to clinical dementia and their risks factors (biomedical, imaging, psychosocial, and clinical) in a community-dwelling elderly with subjective cognitive complaint, through a population-based study. Second, ii) to build the capacity to undertake clinical research on brain aging and dementia disorders and create Data-Bank and Bio-Banks with an appropriate infrastructure to further studies and facilitate access to the data and samples for research.

Methods The Gero cohort aims at recruiting 300 elderly subjects (>70 years) from the community of Santiago (Chile), following them up for at least 3 years. Eligible people are non-demented adults with subjective cognitive complaint, which are reported either by the participant, the proxy or both. Participants are identified through a household census. The protocol of evaluation is based on a multidimensional approach including socio-demographic, biomedical, psychosocial, neuropsychological, neuropsychiatric and motor assessments. Neuroimaging, blood and stool sample samples are also included. This multidimensional evaluation is carried out in a baseline assessment and 3 follow-ups assessment, at 18 and 36 months. In addition, in months 6, 24, and 30, a telephone interview is done in order to keep contact with the participants and to assess general well-being.

Study Overview

Status

Recruiting

Conditions

Detailed Description

Objectives of the Study:

The general objective of this study is to analyze the rate of functional decline (FD) and progression to clinical dementia and their risks factors (biomedical, imaging, psychosocial, and clinical) in a community-dwelling elderly with subjective cognitive complaint (SCC), through a population-based study. The specific objectives are to determinate (i) longitudinal evolution of biomarkers measured from blood, stool and structural and functional neuroimaging (MRI), (ii) evolution of the health-related quality of life; (iii) rate of cardiovascular events (stroke and coronary events), and (iv) mortality rates. The investigators also aim to build the capacity to undertake clinical research on brain aging and dementia disorders and create Data-Bank and Bio-Banks with an appropriate infrastructure to further studies and facilitate access to the data and samples for research.

The Gero cohort is the core clinical project of the GERO, supported by the Fund for Research Centers in Priority Areas Program (FONDAP) of the Chilean National Commission for Scientific and Technological Research (CONICYT). GERO is initially funded for 5 years, and its main aim is to establish a center for studying Brain Aging in Chile including basic and clinical research.

Methods/Design

Field work during the first contact

The recruitment process considers two steps. Firstly, a lay team contacts each home to determine the presence of eligible individuals. In positive cases, the person receives a second visit by a trained psychologist who proceeds to check the eligibility. In case of acceptance, the inclusion and exclusion criteria protocol are applied. If the subject fulfills the criteria, the psychologist schedule a medical interview. Following this evaluation, a neurologist decides if the subject fulfill the inclusion criteria of the cohort.

The fieldwork is preceded by an outreach campaign (flyers, local radio advertisements, and presentations to community-organized groups) raising awareness about the visit of interviewers and the relevance of participating in the study. Rates of contact and response are monitored permanently, and the procedures around the contact and first interview are checked in the field and also by telephone to a subsample of participants. Contact to homes is attempted up to three times on different days and hours before considering it frustrated. The fieldwork started in November 2017 and is expected to finish at the end of 2019.

The lay team and psychologists involved in the first contact and recruitment received specific training on their labour in the field. The lay team completed a whole week training, which included theoretical and practical elements. Psychologists received a twelve weeks length training, which covers several sessions of neuropsychological assessment, including performance psychology.

Sample size

The sample size had to satisfy two criteria, one concerned with the statistical power required to explore multiple associations with outcomes, and other related to the feasibility to perform a wide range of assessments to each participant assuming costs and logistics. Both criteria meant a trade-off between the tolerance to uncertainty around the parameters to be estimated and the number of assessments that would be investigated throughout the study. The final sample chosen was 300 participants. This number allows maintaining the integrity of the original protocol and permits to test associations equivalent to an odds ratio (OR) around 1.5 (Cohen's d equal to 0,22) in cases of exposition and probability of the outcome close to 50%, using a significance of 5%. It is expected to follow each participant between 2 and 3 years, accumulating roughly 750 person-years of follow up.

Follow-up and retention strategy

Socio-demographic, clinical, psychosocial, neuropsychological, neuropsychiatric, motor, neuroimaging, blood biomarkers, stool, and genetic samples will be performed as baseline evaluation and every 18 months, with the exception of genetic study that will be performed only at baseline and neuroimaging at baseline and the 36 month. Patients' health status, functionality, and involvement in the Gero cohort will be monitored every 6 months by a telephonic questionnaire.

To avoid a significant attrition of the sample a set following strategies have been considered: to recruit only people who have at least one person that can facilitate the contact with him or her, it means a person who can be contacted for asking about the location of the participant; telephone contact every six months; and domicile visit in case of absence of contact or attending to assessment appointments. Additionally, all transport costs of participants will be covered by the Gero cohort administration, as well as any food that is required during the days of assessment. Initially, the end of the follow up of the cohort is programmed for October 2022.

Assessments and measurements

The protocol considers an intensive and deep multidimensional study of factors related to the prognosis of FD and dementia development. The range of assessments includes: socio-demographic, psychosocial, neuropsychological, neuropsychiatric, motor, neuroimaging, blood biomarkers, genetic and stool samples to perform gut microbiome studies. Neuroimaging protocol will allow assessing brain atrophy, structural and functional connectivity and white matter lesions. Gero biological samples of whole blood, buffy coat, plasma, serum, and peripheral mononuclear cells are taken and processed according to the guidelines published in 2015. Samples are stored in our Gero biobank for long-term storage at -80 °C or in liquid nitrogen. Stool samples will be collected using standardized kits and DNA extracted using the protocol Q suggested by the international human microbiome standards (IHMS SOP 06 V1). Data are recorded in an ad-hoc platform developed by bioinformatics and bioengineers personal of Gero.

Data analysis plan

The Gero cohort offers a unique opportunity for multiple analyses to identify, correlate and analyze multidimensional factors related to FD and progression to dementia in elderlies with SCC.

In broad terms, a descriptive of baseline measurements (either outcomes or potential predictive factors) will be performed. The procedure will be repeated at each measurement time, every 18 months. Random effect models will be used for describing trajectories of participant subgroups and the whole cohort according to main variables, using Markov-Chain Montecarlo procedures.

The association between variables and outcomes will be explored broadly using different machine learning methods, such as elastic net procedure, random forest procedure, based-tree methods, and support vector machines. These procedures are suitable to lead with multi-collinearity and also high dimensional data (e.g. the number of predictive variables is larger than the number of participants in the cohort). Interpretation of causality will be conducted using standard random effect models and eventually structural equation modeling.

Missing data and loss of follow up of participants are common in observational studies, mainly in cohorts. Firstly, cases with missing data in any outcome will be explored and compared with cases without missing data describing any pattern. Secondly, two strategies will be followed to estimate results: (1) to analyze only cases with complete information (i.e. assuming that missing data is completely at random); and (2) imputing data according to multivariate imputation by chained equation techniques. The analysis will be performed using the statistical software R.

Coordination with local health services

The Gero cohort has been carefully design to avoid undermining the usual care of participants in their common health services facilities. Even more, a linkage between the health assessments provided by the cohort and the usual health care has been promoted.

In cases when the cohort's assessment detects a new health condition (diabetes, depression, hypertension, etc.), participants are derived to the primary healthcare centre of their territory. In case of detection of a significant neurological disorder (dementia syndrome, Parkinson, etc.) the participants are directly derived to specialized care according to their health district, communicating the decision to the primary health care.

Primary care health centres, specialized care polyclinics and the direction of the Health District involved have been informed about the study and jointly the protocol of derivation and communication were established.

Regulation of access to data/biospecimens

The access to data and biospecimens is regulated by the GERO directorate in accordance with the local Institutional Review Board authorization. A bilateral agreement must be signed before sharing of data. Access to the server will not be granted.

Study Type

Observational

Enrollment (Anticipated)

300

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Study Locations

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

70 years and older (Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Sampling Method

Probability Sample

Study Population

The cohort recruits the potential participants from the general population, using a door-to-door strategy. The sample framework corresponds to the territories assigned to three primary healthcare centres selected by convenience according to their socioeconomic heterogeneity, which belong to three different districts in Santiago (Chile): Macul, Peñalolen and La Reina. The sample considered a two-stage selection process. The first stage included a sample of quadrants within each territory, where the contact to all houses was attempted. The second stage proceeded when in a home was found more than one potential eligible participant, choosing one randomly. Territories encompassed a population between 14,937 and 39,458 people. of which between 4.6% and 8.0% is expected to be older than 70.

Description

Inclusion Criteria:

  • 70 years old or older.
  • Presence of a knowledgeable informant and/or presence of a contact that allows the follow up of the participant.
  • Being affiliated to the public health insurance.
  • Subjective cognitive complaint either self-reported or reported by a knowledgeable informant.
  • Clinical Dementia Scale- frontotemporal lobar degeneration (CDR-FTLD) equal or inferior to 0.5.
  • Signed informed consent

Exclusion Criteria:

  • Report of medical diagnosis of dementia.
  • Mini-mental State Examination (MMSE) < 21 and Pfeffer questionnaire >2.
  • Institutionalization (for example, living in an elderly home or a skilled nursing facility)
  • Illiteracy, meaning that is not able to count or to read.
  • Visual and auditory acuity not adequate for neuropsychological testing.
  • Important limitation of mobility incompatible with the availability to be independent in daily life activities or attending a clinical centre for further evaluation.
  • Report of medical diagnosis of Parkinson's disease.
  • Report of medical diagnosis of one or more of the following conditions causing severe impairment in functionality: any psychiatric or neurological disorders, brain tumor, subdural haematoma, progressive supranuclear palsy, or history of head trauma.
  • Report of medical diagnosis of stroke occurred in the last three months.
  • Presence of a fatal disease (less than one year of survival)

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Observational Models: Cohort
  • Time Perspectives: Prospective

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Rate of functional decline and progression to clinical dementia
Time Frame: Changes from baseline at 18 and 36 months.
The protocol considers an intensive and deep multidimensional study of factors related to the prognosis of functional decline and dementia development. The range of assessments includes: sociodemographic, psychosocial, neuropsychological, neuropsychiatric, motor, neuroimaging, blood biomarkers, genetic and stool samples to perform gut microbiome studies.
Changes from baseline at 18 and 36 months.

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Longitudinal evolution of biomarkers and functional neuroimaging (fMRI)
Time Frame: Changes from baseline at 18 and 36 months.
Gero biological samples of whole blood, buffy coat, plasma, serum, and peripheral mononuclear cells are taken and processed according to the guidelines published in 2015. Samples are, stored in our Gero biobank for long-term storage at -80 °C or in liquid nitrogen. Stool samples will be collected using standardized kits and DNA extracted using the protocol Q suggested by the international human microbiome standards (IHMS SOP 06 V1). Neuroimaging protocol will allow assessing brain atrophy, structural and functional connectivity and white matter lesions.
Changes from baseline at 18 and 36 months.
Evolution of the health-related quality of life: EQ3D
Time Frame: Changes from baseline at 18 and 36 months.
Health related quality of life will be assessed using the EQ3D and monitored by a period telephone contact. EQ3D is a standardized instrument for measuring generic health status, where 0% is the worst possible health self-perception and 100% is the best health self-perception.
Changes from baseline at 18 and 36 months.
Rate of cardiovascular events
Time Frame: Changes from baseline at 18 and 36 months.
Changes from baseline at 18 and 36 months.
Mortality rates
Time Frame: Changes from baseline at 18 and 36 months.
Changes from baseline at 18 and 36 months.

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Geroscience Center for Brain Health and Metabolism (Gero)

Investigators

  • Principal Investigator: Andrea Slachevsky, MD, Geroscience Center for Brain health and Metabolism

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

September 25, 2017

Primary Completion (Anticipated)

September 25, 2020

Study Completion (Anticipated)

September 25, 2023

Study Registration Dates

First Submitted

February 3, 2020

First Submitted That Met QC Criteria

February 10, 2020

First Posted (Actual)

February 11, 2020

Study Record Updates

Last Update Posted (Actual)

February 11, 2020

Last Update Submitted That Met QC Criteria

February 10, 2020

Last Verified

February 1, 2020

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • FONDAP 15150012

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

Undecided

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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