Major DepressionADNI-DNCT02434393
Characterizing Cognitive Decline in Late Life Depression: The ADNI Depression Project
An observational study of Major Depression and Late Life Depression (LLD), run by University of Southern California at 2 sites in United States.
Trial summary
The purpose of this research study is to characterize the mechanisms contributing to cognitive impairment and accelerated cognitive decline in Late Life Depression (LLD). This is a non-randomized, observational, non-treatment study that originally launched in 2015, enrolling 133 participants. Read more about this study
- Who is it for?
- Ages 65 years and older
- Conditions the study is for
- Major Depression, Late Life Depression (LLD)
- How many people
- 120 participants
- Where
- 2 sitesUnited States
- Study dates
- 4 Mar 2015to May 2027
- Phase
- Observational
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 65 years and older
- All sexes
- No healthy volunteers
- Older adult
Study population: 120 older adults meeting criteria for Major Depression or Late Life Depression (LLD).
Who may be able to join
- 1. Individual participated in original Characterizing Cognitive Decline in Late Life Depression study or Multimodal MRI Characteristics of Psychotherapy Response in Late Life Depression Study.
Who cannot join
- Antidepressant medication treatment is allowed only if the medication dose is stable for 4 weeks prior to the MRI scan.
- Psychotherapy interventions is allowed only if they have completed at least 4 weeks of individual or group psychotherapy intervention prior to the MRI scan.
- Participants taking cognitive enhancing medications will be able to enter the study.
Trial locations and contacts
2 sites in 1 country. Contact the study team or a site near you to ask about taking part.
United States2 sites, 1 recruiting
- Completed
University of Pittsburgh
Pittsburgh, Pennsylvania, 15213
- Recruiting
University of California, San Francisco
San Francisco, California, 94143
Scott Mackin, Ph.D.
Duygu Tosun, Ph.D.
About this study
Official title: Characterizing Cognitive Decline in Late Life Depression: The Alzheimer's Disease Neuroimaging Initiative - Depression Project
The purpose of this research study is to characterize the mechanisms contributing to cognitive impairment and accelerated cognitive decline in Late Life Depression (LLD).
This is a non-randomized, observational, non-treatment study that originally launched in 2015, enrolling 133 participants. From the originally enrolled participants, the continuation of the ADNI-D study will enroll 120 participants which will include following participants from the original (parent) protocol and enrollment of new participants for a period of 30 months. Data from an additional 300 non-depressed subjects will be used from ADNI studies for comparison.
Depression history, symptom severity and health information will be collected at the initial visit to determine eligibility. An magnetic resonance imaging (MRI) scan, as well as amyloid (florbetapir) and tau (flortaucipr) positron emission tomography (PET) imaging will be conducted at San Francisco VA. Collection of plasma and serum for biomarkers, clinical assessments and cognitive assessments will be conducted at two time points. Blood samples will also be collected for genetic analysis.
- Conditions
- Major Depression, Late Life Depression (LLD)
- Keywords
- Depression, Late Life Depression, LLD, amyloid imaging, biomarkers
- Medical subject headings
- Depressive Disorder, Major, Depression
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
| Study group | Role | What they receive |
|---|---|---|
| Late Life Depression | 120 participants who meet the criteria for Major Depression or Late Life Depression (LLD) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Rate of Change in neuropsychological measures of executive function as measured by the Digit Symbol Substitution Test using total correct.
The Digit Symbol subtest is a measure of attention, working memory, and information processing speed. Participants are presented with a stimulus sheet, and asked to write in the correct symbol that corresponds with a number keyed at the top of the page. A scaled score is calculated based on the number of total correct responses.
Measured: 5 years (parent protocol), 5 years (continuation)
Rate of Change in expressive language as measured by the Boston Naming Test using total correct.
Boston Naming Test is a measure of visual confrontation naming requires the subject to name objects depicted in outline drawings. The drawings are graded in difficulty, with the easiest drawings presented first. If a subject encounters difficulty in naming an object, a stimulus cue and/or a phonemic cue is provided. The number of spontaneous correct responses (maximum score = 30) and spontaneous plus semantically-cued correct responses (maximum score = 30) are recorded. The number of perceptual errors, circumlocutions, paraphasic errors, and perseverations can also be used to evaluate the subjects' language performance.
Measured: 5 years (parent protocol), 5 years (continuation)
Rate of change in learning and memory as measured by the Rey Auditory Verbal Learning Test using total correct and delayed recall.
Rey Auditory Verbal Learning Test (AVLT) is a list learning task which assesses multiple cognitive parameters associated with learning and memory. On each of 5 learning trials, 15 unrelated words (all nouns) are presented orally at the rate of one word per second and immediate free recall of the words is elicited. The number of correctly recalled words on each trial is recorded. Following a 20-minute delay filled with unrelated testing, free recall of the original 15 word list is elicited. Finally, a yes/no recognition test is administered which consists of the original 15 words and 15 randomly interspersed distracter words. The number of target "hits" and false positive responses are recorded.
Measured: 5 years (parent protocol), 5 years (continuation)
Change in brain structure using magnetic resonance imaging (MRI)
MRI will be used to conduct cortical thickness analysis of whole brain and hippocampus utilizing the following sequences: 3D T1-weighted volume, FLAIR, T2*GRE, and Arterial Spin-Labeling (ASL) Perfusion.
Measured: 5 years (parent protocol), 5 years (continuation)
Extent of amyloid deposition as measured by florbetapir
Data from these scans will be collected via standardized uptake value ratios (SUVR) normalized to the cerebellum
Measured: 5 years (parent protocol), 5 years (continuation)
Extent of tau deposition as measured by flortaucipr
Measured: 5 years (continuation)
Secondary outcomes (1)
Use biomarkers data employed in ADNI-2 and the NIA AD (Alzheimer's Disease) Genetics Consortium to determine the genotypes needed for the genome wide association study (GWAS).
Data from participants will be entered into the NIH Genome-Wide database and made available to the scientific community.
Measured: 5 years (parent protocol), 5 years (continuation)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted5 May 2015 (estimated)
- Study start4 Mar 2015
- Primary completionMay 2027 (estimated)
- Study completionMay 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (5)Papers the sponsor has linked to this study.
- Other trials for Major DepressionStudies of the same condition, open and under way.
- More trials run by University of Southern CaliforniaThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Case-control
- Time perspective
- Prospective
- Enrolment
- 120 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University of Southern California
- Sponsor type
- University, hospital or other
- Collaborators
- National Institute of Mental Health (NIMH), University of California, San Francisco, Alzheimer's Therapeutic Research Institute
- Responsible party
- Principal investigator, Paul S. Aisen, University of Southern California
- Investigators
- Scott Mackin, PhD, Study director, University of California, San Francisco
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02434393
- Sponsor's protocol ID
- ADC-048
- Other IDs
- R01MH098062
- Acronym
- ADNI-D
- Status last verified
- Nov 2025
- First submitted
- 24 Dec 2014
- Last updated
- 25 Nov 2025
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Publications
Lyness JM, Niculescu A, Tu X, Reynolds CF 3rd, Caine ED. The relationship of medical comorbidity and depression in older, primary care patients. Psychosomatics. 2006 Sep-Oct;47(5):435-9. doi: 10.1176/appi.psy.47.5.435.
PubMed 16959933McCusker J, Cole M, Ciampi A, Latimer E, Windholz S, Belzile E. Major depression in older medical inpatients predicts poor physical and mental health status over 12 months. Gen Hosp Psychiatry. 2007 Jul-Aug;29(4):340-8. doi: 10.1016/j.genhosppsych.2007.03.007.
PubMed 17591511Gabryelewicz T, Styczynska M, Luczywek E, Barczak A, Pfeffer A, Androsiuk W, Chodakowska-Zebrowska M, Wasiak B, Peplonska B, Barcikowska M. The rate of conversion of mild cognitive impairment to dementia: predictive role of depression. Int J Geriatr Psychiatry. 2007 Jun;22(6):563-7. doi: 10.1002/gps.1716.
PubMed 17136705Rapp MA, Gerstorf D, Helmchen H, Smith J. Depression predicts mortality in the young old, but not in the oldest old: results from the Berlin Aging Study. Am J Geriatr Psychiatry. 2008 Oct;16(10):844-52. doi: 10.1097/JGP.0b013e31818254eb.
PubMed 18827231Ganzini L, Smith DM, Fenn DS, Lee MA. Depression and mortality in medically ill older adults. J Am Geriatr Soc. 1997 Mar;45(3):307-12. doi: 10.1111/j.1532-5415.1997.tb00945.x.
PubMed 9063276
Study at a glance
From the registry record, last updated by the sponsor on 25 Nov 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Characterizing Cognitive Decline in Late Life Depression: The Alzheimer's Disease Neuroimaging Initiative - Depression Project
- ClinicalTrials.gov ID
- NCT02434393
- Acronym / sponsor ID
- ADNI-D / ADC-048
- Conditions
- Major Depression, Late Life Depression (LLD)
- Keywords
- Depression, Late Life Depression, LLD, amyloid imaging, biomarkers
- Study type
- Observational
- Recruitment status
- Recruiting
- Enrolment
- 120 participants (estimated)
- Lead sponsor
- University of Southern CaliforniaUniversity, hospital or other
- Collaborators
- National Institute of Mental Health (NIMH), University of California, San Francisco, Alzheimer's Therapeutic Research Institute
- Study start
- 4 Mar 2015 (actual)
- Primary completion
- May 2027 (estimated)
- Study completion
- May 2027 (estimated)
- First posted
- 5 May 2015 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The purpose of this research study is to characterize the mechanisms contributing to cognitive impairment and accelerated cognitive decline in Late Life Depression (LLD).
This is a non-randomized, observational, non-treatment study that originally launched in 2015, enrolling 133 participants. From the originally enrolled participants, the continuation of the ADNI-D study will enroll 120 participants which will include following participants from the original (parent) protocol and enrollment of new participants for a period of 30 months. Data from an additional 300 non-depressed subjects will be used from ADNI studies for comparison.
Depression history, symptom severity and health information will be collected at the initial visit to determine eligibility. An magnetic resonance imaging (MRI) scan, as well as amyloid (florbetapir) and tau (flortaucipr) positron emission tomography (PET) imaging will be conducted at San Francisco VA. Collection of plasma and serum for biomarkers, clinical assessments and cognitive assessments will be conducted at two time points. Blood samples will also be collected for genetic analysis.
Study design
- Observational model
- Case-control
- Time perspective
- Prospective
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Late Life Depression | – | –120 participants who meet the criteria for Major Depression or Late Life Depression (LLD) |
Who may qualify
- Ages
- 65 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Older adult
- Study population
- 120 older adults meeting criteria for Major Depression or Late Life Depression (LLD).
Key inclusion criteria (1 listed)
- 1. Individual participated in original Characterizing Cognitive Decline in Late Life Depression study or Multimodal MRI Characteristics of Psychotherapy Response in Late Life Depression Study.
Key exclusion criteria (3 listed)
- Antidepressant medication treatment is allowed only if the medication dose is stable for 4 weeks prior to the MRI scan.
- Psychotherapy interventions is allowed only if they have completed at least 4 weeks of individual or group psychotherapy intervention prior to the MRI scan.
- Participants taking cognitive enhancing medications will be able to enter the study.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Primary outcome
Rate of Change in neuropsychological measures of executive function as measured by the Digit Symbol Substitution Test using total correct.
Time frame: 5 years (parent protocol), 5 years (continuation)
The Digit Symbol subtest is a measure of attention, working memory, and information processing speed. Participants are presented with a stimulus sheet, and asked to write in the correct symbol that corresponds with a number keyed at the top of the page. A scaled score is calculated based on the number of total correct responses.
Rate of Change in expressive language as measured by the Boston Naming Test using total correct.
Time frame: 5 years (parent protocol), 5 years (continuation)
Boston Naming Test is a measure of visual confrontation naming requires the subject to name objects depicted in outline drawings. The drawings are graded in difficulty, with the easiest drawings presented first. If a subject encounters difficulty in naming an object, a stimulus cue and/or a phonemic cue is provided. The number of spontaneous correct responses (maximum score = 30) and spontaneous plus semantically-cued correct responses (maximum score = 30) are recorded. The number of perceptual errors, circumlocutions, paraphasic errors, and perseverations can also be used to evaluate the subjects' language performance.
Rate of change in learning and memory as measured by the Rey Auditory Verbal Learning Test using total correct and delayed recall.
Time frame: 5 years (parent protocol), 5 years (continuation)
Rey Auditory Verbal Learning Test (AVLT) is a list learning task which assesses multiple cognitive parameters associated with learning and memory. On each of 5 learning trials, 15 unrelated words (all nouns) are presented orally at the rate of one word per second and immediate free recall of the words is elicited. The number of correctly recalled words on each trial is recorded. Following a 20-minute delay filled with unrelated testing, free recall of the original 15 word list is elicited. Finally, a yes/no recognition test is administered which consists of the original 15 words and 15 randomly interspersed distracter words. The number of target "hits" and false positive responses are recorded.
Change in brain structure using magnetic resonance imaging (MRI)
Time frame: 5 years (parent protocol), 5 years (continuation)
MRI will be used to conduct cortical thickness analysis of whole brain and hippocampus utilizing the following sequences: 3D T1-weighted volume, FLAIR, T2*GRE, and Arterial Spin-Labeling (ASL) Perfusion.
Extent of amyloid deposition as measured by florbetapir
Time frame: 5 years (parent protocol), 5 years (continuation)
Data from these scans will be collected via standardized uptake value ratios (SUVR) normalized to the cerebellum
Extent of tau deposition as measured by flortaucipr
Time frame: 5 years (continuation)
1 secondary outcome
Use biomarkers data employed in ADNI-2 and the NIA AD (Alzheimer's Disease) Genetics Consortium to determine the genotypes needed for the genome wide association study (GWAS).
Time frame: 5 years (parent protocol), 5 years (continuation)
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 25 Nov 2025.
- Background: PubMed 16959933Lyness JM, Niculescu A, Tu X, Reynolds CF 3rd, Caine ED. The relationship of medical comorbidity and depression in older, primary care patients. Psychosomatics. 2006 Sep-Oct;47(5):435-9. doi: 10.1176/appi.psy.47.5.435.
- Background: PubMed 17591511McCusker J, Cole M, Ciampi A, Latimer E, Windholz S, Belzile E. Major depression in older medical inpatients predicts poor physical and mental health status over 12 months. Gen Hosp Psychiatry. 2007 Jul-Aug;29(4):340-8. doi: 10.1016/j.genhosppsych.2007.03.007.
- Background: PubMed 17136705Gabryelewicz T, Styczynska M, Luczywek E, Barczak A, Pfeffer A, Androsiuk W, Chodakowska-Zebrowska M, Wasiak B, Peplonska B, Barcikowska M. The rate of conversion of mild cognitive impairment to dementia: predictive role of depression. Int J Geriatr Psychiatry. 2007 Jun;22(6):563-7. doi: 10.1002/gps.1716.
- Background: PubMed 18827231Rapp MA, Gerstorf D, Helmchen H, Smith J. Depression predicts mortality in the young old, but not in the oldest old: results from the Berlin Aging Study. Am J Geriatr Psychiatry. 2008 Oct;16(10):844-52. doi: 10.1097/JGP.0b013e31818254eb.
- Background: PubMed 9063276Ganzini L, Smith DM, Fenn DS, Lee MA. Depression and mortality in medically ill older adults. J Am Geriatr Soc. 1997 Mar;45(3):307-12. doi: 10.1111/j.1532-5415.1997.tb00945.x.
- National Institute of Mental HealthLink provided by the sponsor.
- Laboratory of Neuro ImagingLink provided by the sponsor.
- Alzheimer's Therapeutic Research InstituteLink provided by the sponsor.
- Related InfoLink provided by the sponsor.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Scott Mackin, PhD study director
University of California, San Francisco
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Major Depression and Late Life Depression (LLD), run by University of Southern California at 2 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 1 inclusion and 3 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 25 Nov 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Nithya Ganesh ((415) 300-0582, nithya.ganesh@ucsf.edu), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Rate of Change in neuropsychological measures of executive function as measured by the Digit Symbol Substitution Test using total correct. (time frame: 5 years (parent protocol), 5 years (continuation)). The study lists 6 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02434393, which also lists 5 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 25 Nov 2025.