Not provided
| ID | Type | Description | Link |
|---|---|---|---|
| 1R01AG081768-01 | U.S. NIH Grant/Contract | View source | |
| 5R01AG081768-02 | U.S. NIH Grant/Contract | View source |
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
| Name | Class |
|---|---|
| University of Parma | OTHER |
| University College Cork | OTHER |
| National Institute on Aging (NIA) | NIH |
| University of California, Los Angeles |
Not provided
Not provided
Not provided
Not provided
Globally, populations are ageing increasing the prevalence of Alzheimer's disease (AD), due to lack of effective treatments. The traditional Mediterranean diet, rich in fibre and polyphenols (PPs) can help prevent or delay cognitive dysfunction and preserve healthy brain structure and function. Cognitive decline is inversely associated with higher PP intakes (>421mg/day) i.e., total flavonoids, flavan-3-ols and flavonoid oligomers. The positive brain effects of flavonoid intake are likely mediated in part by gut microbial PP metabolites, consistent with the emerging role of the brain-gut microbiome (BGM) system in neurodegeneration. Our preliminary data indicate that circulating phenyl-γ-valerolactones (PVL), neuroprotective compounds exclusively produced by gut microbiota from flavan-3-ol rich foods18 are associated with delaying cognitive dysfunction. Intake of PPs change gut microbial composition and function, altering the physiology of the host's secondary bile acid (BA) pool through modulation of bacterial 7α-dehydroxylation of de-conjugated primary BAs into secondary BAs. This is noteworthy as 7α-dehydroxylation of BAs does not happen in the brain and because gut microbial BA metabolites have regulatory and signalling functions in the brain. The ratio between certain primary and secondary BAs is also dysregulated in AD with significantly lower serum concentrations of cholic acid (a primary BA) and increased levels of deoxycholic acid (a bacterially produced secondary BA). The increased ratio of cholic acid to deoxycholic acid is correlated with cognitive decline. Increased levels of tyrosine, tryptophan, purine, and tocopherol have also been identified in postmortem AD brains. However, specific pathways and mechanisms underlying these associations are unclear. In this multi-PI application by leaders in the field of BGM interactions, we leverage the collectively (NIH, HSC, SFI) funded Tripartite US-Ireland R&D Partnership Program to determine the mechanisms involved in PP intake on maintaining healthier cognitive and brain function, as mediated by gut microbiota metabolites of PP and BAs in 50+ year old elderly with enhanced AD risk.
Not provided
Not provided
Not provided
Not provided
Not provided
| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Polyphenol Supplement | Experimental | Juice Plus Essentials, Berry Blend Capsules |
|
| Placebo Supplement | Placebo Comparator |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Polyphenol Supplement | Dietary Supplement | Juice Plus Essentials, Berry Blend Capsules |
|
| Measure | Description | Time Frame |
|---|---|---|
| Differences in Polyphenol-derived metabolite concentrations pre, mid, & post intervention - stool | Measurement of metabolomics via stool specimen. | Collected three times by the participant at home, once at baseline (week 0), once at mid-study (month 6), and once at the final 12month appointment (month 12) |
| Differences in Polyphenol-derived metabolite concentrations pre, mid, & post intervention - blood | Measurement of metabolomics via blood specimen. | Collected three times, once at baseline appointment (week 0), once at mid-study appointment (month 6), and once at the final 12month appointment (month 12). |
| Differences in microbiome levels pre, mid, & post intervention - Stool | 16S RNA sequencing to measure microbiome levels via stool specimen. | Collected three times, once at baseline appointment (week 0), once at mid-study appointment (month 6), and once at the final 12month appointment (month 12). |
| Differences in microbiome levels pre & post intervention - Blood | 16S RNA sequencing to measure microbiome levels via blood specimen. | Collected three times, once at baseline appointment (week 0), once at mid-study appointment (month 6), and once at the final 12month appointment (month 12). |
| Differences in microbiome levels pre, mid, & post intervention - Stool | Shotgun metagenomics, sequencing to measure microbiome levels via stool specimen. | Collected three times, once at baseline appointment (week 0), once at mid-study appointment (month 6), and once at the final 12month appointment (month 12). |
| Differences in microbiome levels pre, mid, & post intervention - Blood |
| Measure | Description | Time Frame |
|---|---|---|
| Differences in tryptophan-associated metabolite profiles pre, mid, and post intervention - Stool | Measurement of tryptophan-associate metabolite profiles via stool specimen. | Collected three times, once at baseline appointment (week 0), once at mid-study appointment (month 6), and once at the final 12month appointment (month 12). |
| Measure | Description | Time Frame |
|---|---|---|
| Differences in Multimodal Brain Signatures pre, mid, & post intervention | Neuroimaging of participants brain via magnetic resonance imaging (MRI) procedure. | Measured thrice, once at baseline (week 0), mid-study (month 6), and final 12month appointment (month 12) visit. |
Inclusion Criteria:
Exclusion Criteria:
Not provided
Not provided
Not provided
Not provided
Not provided
| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Chris Gill, PhD | Contact | +44 28 7012 3181 | c.gill@ulster.ac.uk | |
| Aoife Caffrey, PhD | Contact | +44 (0) 28 701 23401 | a.caffrey@ulster.ac.uk |
| Name | Affiliation | Role |
|---|---|---|
| Chris Gill, PhD | Ulster University, Human Intervention Studies Unit, Coleraine, Co. Londonderry, BT52 1SA, United Kingdom. | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Ulster University, Human Intervention Studies Unit | Recruiting | Coleraine | BT52 1SA | United Kingdom |
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
| ID | Term |
|---|---|
| D060825 | Cognitive Dysfunction |
| D000544 | Alzheimer Disease |
| ID | Term |
|---|---|
| D003072 | Cognition Disorders |
| D019965 | Neurocognitive Disorders |
| D001523 | Mental Disorders |
| D003704 | Dementia |
Not provided
Not provided
| OTHER |
Interventional Model
Not provided
Not provided
Not provided
| Placebo Supplement | Dietary Supplement | Micronutrient matched placebo |
|
Shotgun metagenomics, sequencing to measure microbiome levels via stool specimen. |
| Collected three times, once at baseline appointment (week 0), once at mid-study appointment (month 6), and once at the final 12month appointment (month 12). |
| Differences in Cognitive Measures pre, mid, & post intervention - Executive Function | Administration of a standardized Stroop Neuro-psychological test; participants ability to correctly identify colours when words are printed in conflicting ink colours. | Collected three times, once at baseline appointment (week 0), once at mid-study appointment (month 6), and once at the final 12month appointment (month 12). |
| Differences in Cognitive Measures pre, mid, & post intervention - Executive Function | Administration of a standardized Trails A & B; participants ability to connect dots, in order, as quickly as possible. | Collected three times, once at baseline appointment (week 0), once at mid-study appointment (month 6), and once at the final 12month appointment (month 12). |
| Differences in Cognitive Measures pre, mid, & post intervention | The Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) | Collected three times, once at baseline appointment (week 0), once at mid-study appointment (month 6), and once at the final 12month appointment (month 12). |
| Differences in Cognitive Measures pre, mid, & post intervention | Administration of a standardized arithmetic task; participants ability to complete quick mental math. | Collected three times, once at baseline appointment (week 0), once at mid-study appointment (month 6), and once at the final 12month appointment (month 12). |
| Differences in Bile Acid's (BA's) pre, mid, & post intervention - Stool |
Measurement of BA's via stool specimen. |
| Collected three times, once at baseline appointment (week 0), once at mid-study appointment (month 6), and once at the final 12month appointment (month 12). |
| Differences in Inflammatory markers pre, mid, & post intervention - Blood | Measurement of inflammatory markers via blood specimen. | Collected three times, once at baseline appointment (week 0), once at mid-study appointment (month 6), and once at the final 12month appointment (month 12). |
| Differences in Alzheimer's Disease (AD) markers pre, mid, & post intervention - Blood [Time | Measurement of AD markers via blood specimen. | Collected three times, once at baseline appointment (week 0), once at mid-study appointment (month 6), and once at the final 12month appointment (month 12). |
| Anthropometrics - BMI | Measurement of height(in) and weight(lbs), used to calculate body mass index (BMI) | Measured three times, once at each in-clinic appointment (week 0, month 6, month 12) |
| Questionnaire Data | Use of validated surveys to assess ingestive behaviours, social isolation, stress, health, physical activity, etc., self-reported by the participant at home. | Collected 3 times (1) before beginning the dietary supplement, (2) mid-study month 6, (3) end of study month 12. |
| Monthly Questionnaire Data | Collected once a month for the duration of the study (12months). | Collected 3 times (1) before beginning the dietary supplement, (2) mid-study month 6, (3) end of study month 12. |
| Anthropometrics - waist and hip circumference | Measurement of waist and hip circumference (cm) | Measured three times, once at each in-clinic appointment (week 0, month 6, & month 12) |
| Systolic and Diastolic Blood Pressure | Measurement of the pressure of circulating blood at rest | Measured three times, once at each in-clinic appointment (week 0, month 6, month 12). |
| D001927 |
| Brain Diseases |
| D002493 | Central Nervous System Diseases |
| D009422 | Nervous System Diseases |
| D024801 | Tauopathies |
| D019636 | Neurodegenerative Diseases |