Optimizing CNS DHA Delivery in Elderly Adults at Risk for Dementia

The purpose of this placebo-controlled trial is to compare the effects of 24-weeks supplementation with LPC-DHA and TAG-DHA on cerebrospinal fluid and blood DHA levels, as well as biomarkers of central neurodegenerative and neurotrophic activity, in elderly adults experiencing early signs of cognitive/memory decline including those with mild cognitive impairment (MCI). Extant evidence supports our overarching hypothesis that LPC-DHA supplementation will be more effective than TAG-DHA for increasing central (CSF) DHA levels and improving biomarker profiles in elderly adults. To assess this hypothesis, the following aims are proposed:

SPECIFIC AIM 1: To compare the effects of LPC-DHA and TAG-DHA supplementation on peripheral and CSF DHA levels in elderly adults experiencing early signs of cognitive/memory decline.

SPECIFIC AIM 2: To compare the effects of LPC-DHA and TAG-DHA supplementation on neurotrophic and neurodegenerative biomarkers.

Secondary Aim: To investigate whether changes in CSF DHA levels correlate with changes in objective measures of executive functioning and episodic memory performance.

Study Overview

• Status: Recruiting
• Conditions: Cognitive Decline; Memory Decline; Eldery People; DHA CNS Delivery
• Intervention / Treatment: Dietary supplement: LPC-EPA+DHA capsules containing omega-3 fatty acids EPA and DHA esterified to lysophosphatidylcholine (LPC-EPA+DHA)(Trade name: Lysoveta)

• Study Type: Interventional
• Enrollment (Estimated): 153
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Robert McNamara, PhD; Phone Number: 513-558-6831; Email: mcnamar@ucmail.uc.edu
• Study Contact Backup: Name: Robert Krikorian, PhD; Phone Number: 513-558-6831; Email: KRIKORR@UCMAIL.UC.EDU

Study Locations

• United States
  • Ohio
    • Cincinnati, Ohio, United States, 45219
      • Recruiting
      • University of Cincinnati, Department of Psychiatry and Behavioral Neuroscience
      • Contact: Karen Tugrul; Phone Number: 513-558-6831; Email: tugrulkc@ucmail.uc.edu
      • Contact: Dawn Skirpan; Phone Number: 513-558-8621; Email: skirpadn@ucmail.uc.edu

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. men and women 55 to 82 years old;
2. presence of subjective cognitive decline or mild cognitive decline using the SCD questionnaire, DEX, EMQ, MoCA; and mCDR;
3. No contraindication to a lumbar puncture (LP) unless opting to not have the LP (e.g., thrombocytopenia, coagulopathy, concomitant use of anticoagulant medications, etc.);
4. fluency in English;
5. ability to comprehend and comply with the research protocol; and
6. provision of written informed consent.

Exclusion Criteria:

1. diagnosis of dementia due to AD, Parkinson's disease, frontotemporal dementia, multi-infarct dementia, head trauma with loss of consciousness lasting more than 5 minutes and resulting in persisting functional decline within the three years prior to enrollment, epilepsy, leukoencephalopathy, other neurological conditions that would interfere the study objectives, mMIST <8 or MoCA-MI score <7;
2. self-reported history of any psychotic disorder or bipolar disorder;
3. diagnosis of atrial fibrillation, pancreatic, liver, kidney or hematological coagulation disorder;
4. allergy to shellfish or seafood;
5. current substance use causing physiological dependence or persisting change in functional capability;
6. concomitant, regular use of medications that might affect primary outcome measures or adversely interact with the study product including anticoagulant medications;
7. weekly fish consumption more than 1 x 3 oz servings and/or use of DHA-containing supplements within 3 months prior to screening.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo (mixture of olive oil, corn oil, palm oil); Placebo	Dietary supplement: LPC-EPA+DHA capsules containing omega-3 fatty acids EPA and DHA esterified to lysophosphatidylcholine (LPC-EPA+DHA)(Trade name: Lysoveta); apsules containing omega-3 fatty acids EPA and DHA esterified to lysophosphatidylcholine (LPC-EPA+DHA)(Trade name: Lysoveta)
Active Comparator: fish oil; Fish Oil	Dietary supplement: LPC-EPA+DHA capsules containing omega-3 fatty acids EPA and DHA esterified to lysophosphatidylcholine (LPC-EPA+DHA)(Trade name: Lysoveta); apsules containing omega-3 fatty acids EPA and DHA esterified to lysophosphatidylcholine (LPC-EPA+DHA)(Trade name: Lysoveta)
Experimental: LPC-EPA+DHA (investigational agent) capsules containing omega-3 fatty acids EPA and DHA esterified t; LPC-EPA+DHA (investigational agent) capsules containing omega-3 fatty acids EPA and DHA esterified to lysophosphatidylcholine (LPC-EPA+DHA)(Trade name: Lysoveta)	Dietary supplement: LPC-EPA+DHA capsules containing omega-3 fatty acids EPA and DHA esterified to lysophosphatidylcholine (LPC-EPA+DHA)(Trade name: Lysoveta); apsules containing omega-3 fatty acids EPA and DHA esterified to lysophosphatidylcholine (LPC-EPA+DHA)(Trade name: Lysoveta)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
CSF Docosahexaenoic acid (DHA) levels	Baseline-Endpoint change in CSF docosahexaenoic acid (DHA) composition (g/100 g).	From baseline through week 24

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Amyloid-β1-42 (Aβ42)	Baseline-Endpoint change in blood and CSF amyloid-β1-42 concentrations (ng/ml)	Baseline through week 24
Phospho-tau217 (p-tau217)	Baseline-Endpoint change in blood and CSF p-tau217 concentrations (ng/ml)	Baseline and Week 24
Brain-derived neurotrophic factor (BDNF)	Baseline-Endpoint change in blood and CSF BDNF concentrations (ng/ml)	Baseline and Week 24
Genotyping	APOE alleles (ε2, ε3, ε4) allele frequency	Baseline
California Verbal Learning Test	Objective assessment of episodic memory performance (Units on a scale) Scores range from 0 to 16 for individual learning trials, 0 to 80 for total words recalled across all trials, 0 to 16 for both short and long-delay free recall, and 0 to 16 for total hits. Higher scores indicate better performance on verbal memory	Baseline, Week 12, Week 24
Trail-Making Test, part B	Objective measure of speed of processing/executive functioning (Units on a scale). Scores range from 0 to 300 seconds to complete the task. Lower scores indicate better performance on executive function.	Baseline, week 12, and week 24
Geriatric Depression Scale	Assessment of depression symptom severity (Units on a scale). The score range is from 0 to 15, with higher scores indicating more severe depression.	Screening, Baseline, week 12, and week 24

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Blood glucose levels	Fasting blood glucose concentrations (mg/dL) as a measure of glucose regulation and insulin resistance.	Baseline, week 12, and week 24
Blood insulin levels	Fasting blood insulin concentrations (pmol/L) as a measure of glucose homeostasis and insulin effectiveness.	Baseline, Week 12, week 24
Blood triglycerides levels	Fasting blood triglycerides concentrations (mg/dL)	Baseline, week 12, and week 24
Blood cholesterol levels	Fasting blood cholesterol concentrations (mg/dL)	Baseline, week 12, and week 24
Blood alanine transaminase (ALT) levels	Fasting blood alanine transaminase concentrations (U/L) as a measure of liver function	Baseline, week 12, and week 24
Blood aspartate aminotransferase (AST) levels	Fasting blood aspartate aminotransferase concentrations (U/L) as a measure of liver function	Baseline, week 12, and week 24
Blood C-reactive protein (CRP) levels	Fasting blood C-reactive protein levels concentrations (mg/dL) as a measure of systemic inflammation	Baseline, week 12, and week 24

Collaborators and Investigators

• Sponsor: University of Cincinnati
• Investigators: Principal Investigator: Robert McNamara, PhD, University of Cincinnati

Study record dates

Study Major Dates

• Study Start (Actual): September 15, 2024
• Primary Completion (Estimated): September 15, 2029
• Study Completion (Estimated): September 15, 2029

Study Registration Dates

• First Submitted: December 4, 2024
• First Submitted That Met QC Criteria: April 10, 2025
• First Posted (Actual): April 18, 2025

Study Record Updates

• Last Update Posted (Actual): December 18, 2025
• Last Update Submitted That Met QC Criteria: December 10, 2025
• Last Verified: December 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Mental Disorders; Neurocognitive Disorders; Cognition Disorders; Cognitive Dysfunction
• Other Study ID Numbers: CNS DHA Delivery

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
• product manufactured in and exported from the U.S.: No