Characterizing Cognitive Decline in Late Life Depression: The ADNI Depression Project (ADNI-D)

• ClinicalTrials.gov Identifier: NCT02434393
• Recruitment Status: Active, not recruiting
• First Posted: May 5, 2015
• Last Update Posted: October 21, 2022
• Sponsor: University of Southern California
• Collaborators: National Institute of Mental Health (NIMH); University of California, San Francisco; Alzheimer's Therapeutic Research Institute
• Information provided by (Responsible Party): Paul Aisen, University of Southern California

Tracking Information

• First Submitted Date: December 24, 2014
• First Posted Date: May 5, 2015
• Last Update Posted Date: October 21, 2022
• Actual Study Start Date: March 4, 2015
• Estimated Primary Completion Date: May 2027 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: June 30, 2015)

• Rate of Change in neuropsychological measures of executive function as measured by the Digit Symbol Substitution Test using total correct. [ Time Frame: 5 years ]
  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 ]
  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 ]
  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: 2.5 years ]
  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 F 18: Datum of these scans will be collected via standardized uptake value ratios (SUVR) normalized to the cerebellum [ Time Frame: 2.5 years ]

Original Primary Outcome Measures (submitted: May 4, 2015)

• Rate of Change in neuropsychological measures of executive function as measured by the Digit Symbol Substitution Test using total correct. [ Time Frame: 5 years ]
  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 ]
  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 ]
  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.
• Cortical thickness analysis of whole brain, hippocampus and other structural MRI measures will be utilized and consist of the following sequences: 3D T1-weighted volume, FLAIR, T2*GRE, and Arterial Spin-Labeling (ASL) Perfusion. [ Time Frame: 2.5 years ]
• Extent of amyloid deposition as measured by Florbetapir F 18: Datum of these scans will be collected via standardized uptake value ratios (SUVR) normalized to the cerebellum [ Time Frame: 2.5 years ]

Current Secondary Outcome Measures (submitted: May 4, 2015)

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: 2.5 years ]

Data from participants will be entered into the NIH Genome-Wide database and made available to the scientific community.

• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Characterizing Cognitive Decline in Late Life Depression: The ADNI Depression Project
• Official Title: Characterizing Cognitive Decline in Late Life Depression: The Alzheimer's Disease Neuroimaging Initiative - Depression Project

Brief 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. One hundred and twenty (120) subjects who meet criteria for Major Depression or LLD will be enrolled 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 psychiatric visit to determine eligibility. A 3 Tesla (3T) Magnetic resonance imaging (MRI) scan and florbetapir (18F-AV-45) amyloid imaging will be conducted at the ADNI clinic site visits. 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.

• Detailed Description: Not Provided
• Study Type: Observational
• Study Design: Observational Model: Case-Control; Time Perspective: Prospective
• Target Follow-Up Duration: Not Provided

Biospecimen

Retention:   Samples With DNA

Description:

blood, urine

• Sampling Method: Probability Sample
• Study Population: 120 older adults meeting criteria for Major Depression or Late Life Depression (LLD).

Condition

• Major Depression
• Late Life Depression (LLD)

• Intervention: Not Provided

Study Groups/Cohorts

Late Life Depression

120 participants who meet the criteria for Major Depression or Late Life Depression (LLD)

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.
• McCusker 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.
• Gabryelewicz 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.
• Rapp 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.
• Ganzini 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.

Recruitment Information

• Recruitment Status: Active, not recruiting
• Actual Enrollment (submitted: December 6, 2017): 133
• Original Estimated Enrollment (submitted: May 4, 2015): 120
• Estimated Study Completion Date: May 2027
• Estimated Primary Completion Date: May 2027 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

1. Current DSM-IV diagnosis of Major Depressive Disorder, unipolar type, without psychotic features and six week minimum duration of current depressive episode.
2. English Speaking
3. 65+ years of age
4. Hamilton Depression Rating Scale score ≥ 15
5. Able to give informed consent
6. Willing to undergo one MRI (3 Tesla) and one PET scan (Amyloid imaging)
7. Able to fit in an MRI machine comfortably (BMI ≤ 38)
8. Agrees to collection of blood for GWAS, apolipoprotein E (APOE) testing and DNA and RNA testing
9. Agrees to collection of blood for biomarker testing
10. Agrees to collection of additional blood sample for to-be-determined assays and telomere length measurement
11. Visual and auditory acuity adequate for neuropsychological testing
12. Completed six grades of education or has established work history (sufficient to exclude mental retardation)
13. Study partner is available who has frequent contact with the subject (e.g. an average of 10 hours per week or more), and can accompany the subject to clinical visits for the duration of the protocol.

Exclusion Criteria:

1. Current diagnosis of other axis 1 psychiatric disorders (with the exception of Simple Phobias and Generalized Anxiety Disorder)
2. Evidence of Dementia (MMSE <25)
3. Any electroconvulsive therapy within the past 6 months
4. Undergoing anti-depressant or psychotherapy treatment (exceptions listed 4.3. Treatment Exclusion Exceptions)
5. Any significant neurological diseases (i.e. Parkinson's disease, epilepsy, cortical stroke, traumatic brain injury)
6. History of alcohol or substance abuse or dependence within the past 2 years (DSM-IV criteria)
7. Any active and serious suicidal ideation, including ideation, plan and intent to carry out that plan, as assessed by the Hamilton Depression Rating Scale (HDRS)
8. Any significant systemic illness or unstable medical condition which could lead to difficulty complying with the protocol
9. History of surgical procedures effecting study outcomes
10. Residence in skilled nursing facility
11. Participation in clinical studies involving the same neuropsychological measures used in ADNI-D that may impact study outcomes
12. Investigational agents are prohibited one month prior to entry and for the duration of the trial
13. Exclusion for amyloid imaging with florbetapir: Current or recent participation in any procedures involving radioactive agents such that the total radiation dose exposure to the subject in any given year would exceed the limits of annual and total dose commitment set forth in the US Code of Federal Regulations (CFR) Title 21 Section 361.1
14. Known history of MRI scans with evidence of infection, infarction, or other focal lesions. Subjects with multiple lacunes or lacunes in a critical memory structure are excluded
15. Presence of pacemakers, aneurysm clips, artificial heart valves, ear implants, metal fragments or foreign objects in the eyes, skin or body, claustrophobia
16. Pregnant, lactating, or of childbearing potential (i.e. women must be two years post-menopausal or surgically sterile)

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 65 Years and older (Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT02434393
• Other Study ID Numbers: ADC-048; R01MH098062 ( U.S. NIH Grant/Contract )
• Has Data Monitoring Committee: No
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Current Responsible Party: Paul Aisen, University of Southern California
• Original Responsible Party: Alzheimer's Disease Cooperative Study (ADCS)
• Current Study Sponsor: University of Southern California
• Original Study Sponsor: Alzheimer's Disease Cooperative Study (ADCS)

Collaborators

• National Institute of Mental Health (NIMH)
• University of California, San Francisco
• Alzheimer's Therapeutic Research Institute

Investigators

• Study Director: Rema Raman, PhD; USC Alzheimer's Therapeutic Research Institute
• Study Director: Scott Mackin, PhD; University of California, San Francisco

• PRS Account: University of Southern California
• Verification Date: October 2022