Alzheimer Disease
Conditions
Keywords
disease /disorder proneness /risk, family genetics, genetic counseling, genetic marker, genetic polymorphism, genetic screening, genetic susceptibility
Brief summary
The purpose of this study is to provide healthy adults with genetic testing and information about their chances of developing Alzheimer's disease.
Detailed description
Alzheimer's disease is a common condition affecting memory and thinking. Genes can sometimes be used to provide risk estimates for the eventual development of certain common diseases. Apolipoprotein E (APOE) is one gene that has been identified which can provide information about a person's chances of developing Alzheimer's diseases. Previous research explored the behavioral and psychological impact of receiving genetic risk information for Alzheimer's disease (AD). The REVEAL I Study, funded in 1999, showed that an Alzheimer's disease genetic risk assessment can be given to relatives of people with AD in a safe way. REVEAL II, which was funded in 2003, demonstrated that this same information can be given in a condensed education and counseling protocol without causing severe psychological harm. REVEAL III will further study different ways of providing genetic risk information for Alzheimer's disease. Participation in this study will entail an initial screening phone call to determine eligibility, followed by a phone interview which will ask about demographic information and thoughts and feelings about AD. Participants will complete a mailed survey. Following completion of the survey, a genetic counselor will meet with the participant at the clinic to review family and medical history, administer additional questionnaires asking about AD and genetic testing, and draw blood for genetic testing. Results will be disclosed either in person or over the phone about 3 to 4 weeks later. The genetic counselor will make a brief follow-up phone call 1 week after that. The participant will visit the clinic twice to provide additional information, at 6 weeks and 6 months after disclosure. Finally, the participant will complete a mailed 12 month survey, and the genetic counselor will make a brief follow-up phone call.
Interventions
BEHAVIORALPleiotropic info, in-person disclosure
Individuals are provided with a lifetime percentage risk of developing Alzheimer's disease based on APOE genotyping as well as additional pleiotropic information. Genetic counselors communicate results to participants during an in-person disclosure session.
BEHAVIORALAD-only info, in-person disclosure
Individuals are provided with a lifetime percentage risk of developing Alzheimer's disease based on APOE genotyping. Genetic counselors communicate results to participants during an in-person disclosure session.
BEHAVIORALPleiotropic info, phone disclosure
Individuals are provided with a lifetime percentage risk of developing Alzheimer's disease based on APOE genotyping as well as additional pleiotropic information. Genetic counselors communicate results to participants during a telephone disclosure session.
BEHAVIORALAD-only info, phone disclosure
Individuals are provided with a lifetime percentage risk of developing Alzheimer's disease based on APOE genotyping. Genetic counselors communicate results to participants during an in-person disclosure session.
Sponsors
National Human Genome Research Institute (NHGRI)
Brigham and Women's Hospital
Study design
Allocation
RANDOMIZED
Intervention model
FACTORIAL
Primary purpose
HEALTH_SERVICES_RESEARCH
Masking
SINGLE (Subject)
Eligibility
Sex/Gender
ALL
Age
18 Years to 85 Years
Healthy volunteers
Yes
Inclusion criteria
* Aged 18 years to 85 years old
Exclusion criteria
* Unable to visit a study site * Current untreated depression or anxiety * Family history of AD diagnosed under age 60 * More than one first-degree relative diagnosed with AD (e.g. Mother and brother)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Center for Epidemiological Studies-Depression Scale (CES-D) | 6 weeks, 6 months, and 12 months post-disclosure | A 20-item scale measuring general depression. Scores range from 0-60, with higher scores indicating greater general depression. |
| Beck Anxiety Inventory (BAI) | 6 weeks, 6 months, 12 months post-disclosure | A 21-item scale measuring general anxiety. Scores range from 0-63, with higher scores indicating greater anxiety. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Impact of Events Scale (IES) | 6 weeks, 6 months, 12 months post-disclosure | A 15-item scale measuring distress specific to the test results received. Scores range from 0-75, with higher scores indicating greater test-related distress. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Pleiotropic Info, In-person Disclosure Incidental pleiotropic risk information, in addition to AD risk information, is disclosed in-person during an APOE-based genetic risk assessment
Pleiotropic info, in-person disclosure: Individuals are provided with a lifetime percentage risk of developing Alzheimer's disease based on APOE genotyping as well as additional pleiotropic information.
Genetic counselors communicate results to participants during an in-person disclosure session. | 64 |
| AD-only Info, Phone Disclosure Alzheimer's disease risk information only is disclosed via telephone during an APOE-based genetic risk assessment
AD-only info, phone disclosure: Individuals are provided with a lifetime percentage risk of developing Alzheimer's disease based on APOE genotyping.
Genetic counselors communicate results to participants during an in-person disclosure session. | 70 |
| Pleiotropic Info, Phone Disclosure Incidental pleiotropic risk information, in addition to AD risk information, is disclosed via telephone during an APOE-based genetic risk assessment
Pleiotropic info, phone disclosure: Individuals are provided with a lifetime percentage risk of developing Alzheimer's disease based on APOE genotyping as well as additional pleiotropic information.
Genetic counselors communicate results to participants during a telephone disclosure session. | 55 |
| AD-only Info, In-person Disclosure Alzheimer's disease risk information only is disclosed in-person during an APOE-based genetic risk assessment
AD-only info, in-person disclosure: Individuals are provided with a lifetime percentage risk of developing Alzheimer's disease based on APOE genotyping.
Genetic counselors communicate results to participants during an in-person disclosure session. | 68 |
| Total | 257 |
Baseline characteristics
| Characteristic | AD-only Info, Phone Disclosure | Pleiotropic Info, In-person Disclosure | Pleiotropic Info, Phone Disclosure | AD-only Info, In-person Disclosure | Total |
|---|---|---|---|---|---|
| Age, Continuous | 57 years STANDARD_DEVIATION 13 | 57 years STANDARD_DEVIATION 12 | 59 years STANDARD_DEVIATION 13 | 59 years STANDARD_DEVIATION 12 | 58 years STANDARD_DEVIATION 13 |
| Anxiety (Beck Anxiety Index: BAI) | 3.6 units on a scale STANDARD_DEVIATION 3.4 | 2.7 units on a scale STANDARD_DEVIATION 2.9 | 3.8 units on a scale STANDARD_DEVIATION 3.7 | 4.0 units on a scale STANDARD_DEVIATION 3.8 | 3.5 units on a scale STANDARD_DEVIATION 3.5 |
| Depression (Center for Epidemiological Studies Depression Scale: CES-D) | 5.5 units on a scale STANDARD_DEVIATION 5.4 | 5.1 units on a scale STANDARD_DEVIATION 4.6 | 5.5 units on a scale STANDARD_DEVIATION 5 | 6.6 units on a scale STANDARD_DEVIATION 5.3 | 5.7 units on a scale STANDARD_DEVIATION 5.1 |
| Race (NIH/OMB) American Indian or Alaska Native | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 13 Participants | 5 Participants | 4 Participants | 16 Participants | 38 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 1 Participants | 0 Participants | 1 Participants | 1 Participants | 3 Participants |
| Race (NIH/OMB) White | 55 Participants | 59 Participants | 50 Participants | 51 Participants | 215 Participants |
| Region of Enrollment United States | 70 participants | 64 participants | 55 participants | 68 participants | 257 participants |
| Sex: Female, Male Female | 39 Participants | 36 Participants | 29 Participants | 37 Participants | 141 Participants |
| Sex: Female, Male Male | 31 Participants | 28 Participants | 26 Participants | 31 Participants | 116 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — | — / — |
| other Total, other adverse events | 8 / 64 | 9 / 70 | 4 / 55 | 5 / 68 |
| serious Total, serious adverse events | 1 / 64 | 0 / 70 | 0 / 55 | 0 / 68 |
Outcome results
Primary
Beck Anxiety Inventory (BAI)
A 21-item scale measuring general anxiety. Scores range from 0-63, with higher scores indicating greater anxiety.
Time frame: 6 weeks, 6 months, 12 months post-disclosure
Population: Number of participants analyzed are the number of participants who received genetic risk information and completed the 6-week follow-up (256). At 6 months, 252 participants provided data. At 12 months, 247 participants provided data.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Pleiotropic Info, In-person Disclosure | Beck Anxiety Inventory (BAI) | 12 Months | 3.4 score on a scale | Standard Deviation 5.5 |
| Pleiotropic Info, In-person Disclosure | Beck Anxiety Inventory (BAI) | 6 Weeks | 2.9 score on a scale | Standard Deviation 3.6 |
| Pleiotropic Info, In-person Disclosure | Beck Anxiety Inventory (BAI) | 6 Months | 3.4 score on a scale | Standard Deviation 5.4 |
| AD-only Info, Phone Disclosure | Beck Anxiety Inventory (BAI) | 6 Months | 3.4 score on a scale | Standard Deviation 4.3 |
| AD-only Info, Phone Disclosure | Beck Anxiety Inventory (BAI) | 6 Weeks | 4.1 score on a scale | Standard Deviation 5.4 |
| AD-only Info, Phone Disclosure | Beck Anxiety Inventory (BAI) | 12 Months | 4.0 score on a scale | Standard Deviation 5.3 |
| Pleiotropic Info, Phone Disclosure | Beck Anxiety Inventory (BAI) | 6 Months | 3.3 score on a scale | Standard Deviation 3.8 |
| Pleiotropic Info, Phone Disclosure | Beck Anxiety Inventory (BAI) | 6 Weeks | 3.2 score on a scale | Standard Deviation 4.2 |
| Pleiotropic Info, Phone Disclosure | Beck Anxiety Inventory (BAI) | 12 Months | 3.5 score on a scale | Standard Deviation 3.4 |
| AD-only Info, In-person Disclosure | Beck Anxiety Inventory (BAI) | 6 Weeks | 3.1 score on a scale | Standard Deviation 3.3 |
| AD-only Info, In-person Disclosure | Beck Anxiety Inventory (BAI) | 12 Months | 3.8 score on a scale | Standard Deviation 4.8 |
| AD-only Info, In-person Disclosure | Beck Anxiety Inventory (BAI) | 6 Months | 3.0 score on a scale | Standard Deviation 5 |
Primary
Center for Epidemiological Studies-Depression Scale (CES-D)
A 20-item scale measuring general depression. Scores range from 0-60, with higher scores indicating greater general depression.
Time frame: 6 weeks, 6 months, and 12 months post-disclosure
Population: Number of participants analyzed are the number of participants who received genetic risk information and completed the 6-week follow-up (256). At 6 months, 252 participants provided data. At 12 months, 247 participants provided data.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Pleiotropic Info, In-person Disclosure | Center for Epidemiological Studies-Depression Scale (CES-D) | 6 Weeks | 4.8 score on a scale | Standard Deviation 5 |
| Pleiotropic Info, In-person Disclosure | Center for Epidemiological Studies-Depression Scale (CES-D) | 12 Months | 7.1 score on a scale | Standard Deviation 8.2 |
| Pleiotropic Info, In-person Disclosure | Center for Epidemiological Studies-Depression Scale (CES-D) | 6 Months | 5.5 score on a scale | Standard Deviation 7 |
| AD-only Info, Phone Disclosure | Center for Epidemiological Studies-Depression Scale (CES-D) | 6 Weeks | 7.0 score on a scale | Standard Deviation 8.4 |
| AD-only Info, Phone Disclosure | Center for Epidemiological Studies-Depression Scale (CES-D) | 12 Months | 7.6 score on a scale | Standard Deviation 9 |
| AD-only Info, Phone Disclosure | Center for Epidemiological Studies-Depression Scale (CES-D) | 6 Months | 6.6 score on a scale | Standard Deviation 6.7 |
| Pleiotropic Info, Phone Disclosure | Center for Epidemiological Studies-Depression Scale (CES-D) | 6 Months | 5.8 score on a scale | Standard Deviation 6.4 |
| Pleiotropic Info, Phone Disclosure | Center for Epidemiological Studies-Depression Scale (CES-D) | 6 Weeks | 6.4 score on a scale | Standard Deviation 6.4 |
| Pleiotropic Info, Phone Disclosure | Center for Epidemiological Studies-Depression Scale (CES-D) | 12 Months | 7.1 score on a scale | Standard Deviation 7 |
| AD-only Info, In-person Disclosure | Center for Epidemiological Studies-Depression Scale (CES-D) | 6 Weeks | 5.5 score on a scale | Standard Deviation 5.4 |
| AD-only Info, In-person Disclosure | Center for Epidemiological Studies-Depression Scale (CES-D) | 12 Months | 6.2 score on a scale | Standard Deviation 6.9 |
| AD-only Info, In-person Disclosure | Center for Epidemiological Studies-Depression Scale (CES-D) | 6 Months | 6.1 score on a scale | Standard Deviation 6.6 |
Secondary
Impact of Events Scale (IES)
A 15-item scale measuring distress specific to the test results received. Scores range from 0-75, with higher scores indicating greater test-related distress.
Time frame: 6 weeks, 6 months, 12 months post-disclosure
Population: Number of participants analyzed are the number of participants who received genetic risk information and completed the 6-week follow-up (256). At 6 months, 252 participants provided data. At 12 months, 247 participants provided data.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Pleiotropic Info, In-person Disclosure | Impact of Events Scale (IES) | 6 Weeks | 3.4 score on a scale | Standard Deviation 6.4 |
| Pleiotropic Info, In-person Disclosure | Impact of Events Scale (IES) | 12 Months | 2.4 score on a scale | Standard Deviation 5.9 |
| Pleiotropic Info, In-person Disclosure | Impact of Events Scale (IES) | 6 Months | 3.5 score on a scale | Standard Deviation 8.7 |
| AD-only Info, Phone Disclosure | Impact of Events Scale (IES) | 6 Weeks | 4.5 score on a scale | Standard Deviation 7.9 |
| AD-only Info, Phone Disclosure | Impact of Events Scale (IES) | 12 Months | 4.0 score on a scale | Standard Deviation 10.4 |
| AD-only Info, Phone Disclosure | Impact of Events Scale (IES) | 6 Months | 4.0 score on a scale | Standard Deviation 8.2 |
| Pleiotropic Info, Phone Disclosure | Impact of Events Scale (IES) | 6 Months | 3.0 score on a scale | Standard Deviation 4.2 |
| Pleiotropic Info, Phone Disclosure | Impact of Events Scale (IES) | 6 Weeks | 3.7 score on a scale | Standard Deviation 6.3 |
| Pleiotropic Info, Phone Disclosure | Impact of Events Scale (IES) | 12 Months | 2.5 score on a scale | Standard Deviation 5.2 |
| AD-only Info, In-person Disclosure | Impact of Events Scale (IES) | 6 Weeks | 3.8 score on a scale | Standard Deviation 7.7 |
| AD-only Info, In-person Disclosure | Impact of Events Scale (IES) | 12 Months | 3.3 score on a scale | Standard Deviation 7.4 |
| AD-only Info, In-person Disclosure | Impact of Events Scale (IES) | 6 Months | 3.2 score on a scale | Standard Deviation 5.8 |