Characterizing Cognitive Decline in Late Life Depression: The ADNI Depression Project

Major Depression Clinical Trial

— ADNI-D  

Official title:

Characterizing Cognitive Decline in Late Life Depression: The Alzheimer's Disease Neuroimaging Initiative - Depression Project

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT02434393
• Other study ID #: ADC-048
• Secondary ID: R01MH098062
• Status: Active, not recruiting
• Start date: March 4, 2015
• Est. completion date: May 2027

Study information

• Verified date: October 2022
• Source: University of Southern California
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical 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. 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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 133
• Est. completion date: May 2027
• Est. primary completion date: May 2027
• Accepts healthy volunteers: No
• Gender: All
• Age group: 65 Years and older

Eligibility

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)

Related Conditions & MeSH terms

• Cognitive Dysfunction
• Depression
• Depressive Disorder
• Late Life Depression (LLD)
• Major Depression

Locations

Country	Name	City	State
United States	University of Pittsburgh	Pittsburgh	Pennsylvania
United States	University of California, San Francisco	San Francisco	California

Sponsors (4)

Lead Sponsor	Collaborator
University of Southern California	Alzheimer's Therapeutic Research Institute, National Institute of Mental Health (NIMH), University of California, San Francisco

Country where clinical trial is conducted

United States, 

References & Publications (5)

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.	5 years
Primary	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.	5 years
Primary	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.	5 years
Primary	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.	2.5 years
Primary	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		2.5 years
Secondary	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.	2.5 years

External Links

•   Alzheimer's Therapeutic Research Institute
•   Laboratory of Neuro Imaging
•   National Institute of Mental Health