Probiotic Milk Drink for Gut and Brain Health in Older Adults and Caregivers (PFM)
A Novel Probiotic Fermented Milk Drink to Improve Gut and Brain Health in Older Floridians and Their Caregivers
This double-blind, randomized, placebo-controlled clinical trial will evaluate the effects of a probiotic fermented milk (PFM) drink on gut and brain health in individuals with Alzheimer's disease and related dementias (ADRD) and their caregivers. Up to 40 participants will be enrolled.
Participants will be randomly assigned to consume either the PFM drink or a matched placebo daily for 30 days. The primary objective is to determine whether PFM consumption improves gut microbiome abnormalities. Secondary objectives include evaluating effects on nutrient absorption, gut microbiome diversity and composition, and systemic inflammation. The study will also explore relationships between changes in nutrient absorption, microbiome profiles, inflammation, and behavioral outcomes in participants with ADRD and their caregivers.
Each participant will participate in the study for approximately 30 days. This pilot study is intended to generate preliminary clinical and biological data regarding the potential role of probiotic nutrition in supporting gut and brain health and to inform the design of future larger clinical trials.
Descripción general del estudio
Estado
Condiciones
Intervención / Tratamiento
Descripción detallada
This pilot clinical trial will investigate the effects of a human-origin probiotic fermented milk (PFM) beverage on biological pathways related to gut and brain health in individuals with Alzheimer's disease and related dementias (ADRD) and their caregivers. The study is based on evidence suggesting that alterations in the gut microbiome, nutrient metabolism, and systemic inflammation may be associated with cognitive and behavioral health and may represent modifiable targets in ADRD.
Participants with ADRD and their caregivers will be enrolled as patient-caregiver dyads and independently randomized to receive either the PFM intervention or a matched placebo for 30 days. The PFM contains four human-origin probiotic strains: Limosilactobacillus reuteri HL278, Lactiplantibacillus plantarum HL279, Lacticaseibacillus paracasei HL260, and Lactiplantibacillus plantarum HL82.
Biological assessments will be performed before and after the intervention to characterize changes in the gut microbiome, nutrient-related measures, and systemic inflammation. Fecal microbiome composition will be evaluated using metagenomic sequencing and bioinformatics approaches to examine microbial diversity and taxonomic composition. Blood- and stool-based laboratory analyses will be used to assess selected nutrient and inflammatory biomarkers.
Clinical and behavioral measures will also be evaluated to explore whether biological changes associated with the intervention are related to measures of health, quality of life, agitation, stress, or anxiety in participants with ADRD and their caregivers. Analyses will compare changes between the PFM and placebo groups and explore relationships among microbiome characteristics, nutrient-related measures, inflammatory markers, and behavioral outcomes.
The study is intended to generate preliminary information regarding the biological effects and feasibility of the PFM intervention and to provide data that may inform the design of larger future clinical trials.
Tipo de estudio
Inscripción (Estimado)
Fase
- No aplica
Contactos y Ubicaciones
Estudio Contacto
- Nombre: Hariom Yadav, PhD
- Número de teléfono: 8139748222
- Correo electrónico: hyadav@usf.edu
Copia de seguridad de contactos de estudio
- Nombre: Shalini Jain, PhD
- Número de teléfono: 813-9746281
- Correo electrónico: jains10@usf.edu
Ubicaciones de estudio
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Florida
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Tampa, Florida, Estados Unidos, 33612
- Center for Microbiome Research, Microbiomes Institute, University of South Florida, Tampa, FL, 33620
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Investigador principal:
- Hariom Yadav, PhD
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Investigador principal:
- Shalini Jain, PhD
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Contacto:
- Shalini Jain, PhD
- Número de teléfono: 813-9746281
- Correo electrónico: jains10@usf.edu
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Contacto:
- Dhananjay Yadav, PhD
- Número de teléfono: 8134521781
- Correo electrónico: dhananjay11@usf.edu
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Criterios de participación
Criterio de elegibilidad
Edades elegibles para estudiar
- Adulto
- Adulto Mayor
Acepta Voluntarios Saludables
Descripción
Inclusion Criteria:• Diagnosed with ADRD and accompanied with their caregiver
- Age ≥ 18 years old
- Willing to consume PFM and/or willing to consume placebo drink, follow instructions of study team and sign consent form
Exclusion Criteria:
- Lactose intolerance or another intolerance that prevents the safe consumption of dairy products
- Allergy to any ingredients in the PFM formulations, including almonds/nuts, lactose/dairy, dextrose, artificial sweeteners, or dyes used in flavoring
- Known allergy or hypersensitivity to peanuts or soy, as indicated on the pectin product label.
- Known allergy, intolerance, or hypersensitivity to Ensure® or any of its components.
- Cancer patients receiving chemotherapy, due to potential increased risk of infection from GI tract damage
- Participants who require systemic antibiotics after randomization will have the antibiotic use documented and will be withdrawn due to potential effects on the gut microbiome. Data collected prior to antibiotic use may be retained, and withdrawn participants will be replaced to maintain the target sample size.
- Major surgery(ies) of the gut or brain within the past five years
- Diagnosis of inflammatory bowel disease (IBD), ulcerative colitis, Crohn's disease, acid reflux, gastroesophageal reflux disease (GERD), Clostridium difficile infection (CDI), or any other gastrointestinal disease that could significantly change the microbiome History of fecal microbiota transplantation
- Small intestinal bacterial overgrowth
- History of anticipatory nausea, vomiting, constipation, or diarrhea
Antibiotic or probiotic or heavy yogurt (3 servings per day) use within the past 30 days
o Probiotic use is defined as consumption of ≥108 CFU/day, in the form of tablets, capsules, lozenges, powders, or dairy products in which probiotics are a major ingredient
- Critical or terminal illnesses including diabetes
- Pregnant women will be excluded from the study based on self-report during the screening process. No pregnancy testing kits will be provided, and pregnancy testing will not be performed as part of this study. Therefore, individuals who are currently pregnant are excluded from participation.
- Significant mental health conditions
Plan de estudios
¿Cómo está diseñado el estudio?
Detalles de diseño
- Propósito principal: Tratamiento
- Asignación: Aleatorizado
- Modelo Intervencionista: Asignación paralela
- Enmascaramiento: Cuadruplicar
Armas e Intervenciones
Grupo de participantes/brazo |
Intervención / Tratamiento |
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Experimental: Probiotics fermented milk
Participants will receive two 4-ounce servings of a probiotic fermented milk (PFM) drink daily for 30 days. The PFM drink contains probiotic strains intended to support gut microbiome balance, nutrient absorption, and gut-brain health. Participants will receive two 4-ounce servings of a placebo drink daily for 30 days. The placebo drink is matched in taste, appearance, and volume but does not contain active probiotic components. |
A human-origin probiotic fermented milk (PFM) drink has been developed for this clinical study.
Over 1,000 human-derived probiotic strains were screened for gut and brain health effects using C. elegans, identifying 36 promising strains.
These were further evaluated for growth in milk, fermentation capacity (pH reduction and coagulation), and effects on healthspan.
Four strains with strong performance were selected: Limosilactobacillus reuteri HL278, Lactiplantibacillus plantarum HL279, Lacticaseibacillus paracasei HL260, and Lactiplantibacillus plantarum HL82.
A multi-strain formulation was produced in a dedicated facility.
The final PFM contains GRAS-designated probiotic strains and is manufactured for research use only in this study.
Participants will receive two 4-ounce servings of a placebo drink daily for 30 days.
The placebo drink is matched in taste, appearance, and volume but does not contain active probiotic components.
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Comparador de placebos: Placebo milk
ADRD and caregivers
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A human-origin probiotic fermented milk (PFM) drink has been developed for this clinical study.
Over 1,000 human-derived probiotic strains were screened for gut and brain health effects using C. elegans, identifying 36 promising strains.
These were further evaluated for growth in milk, fermentation capacity (pH reduction and coagulation), and effects on healthspan.
Four strains with strong performance were selected: Limosilactobacillus reuteri HL278, Lactiplantibacillus plantarum HL279, Lacticaseibacillus paracasei HL260, and Lactiplantibacillus plantarum HL82.
A multi-strain formulation was produced in a dedicated facility.
The final PFM contains GRAS-designated probiotic strains and is manufactured for research use only in this study.
Participants will receive two 4-ounce servings of a placebo drink daily for 30 days.
The placebo drink is matched in taste, appearance, and volume but does not contain active probiotic components.
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¿Qué mide el estudio?
Medidas de resultado primarias
Medida de resultado |
Medida Descripción |
Periodo de tiempo |
|---|---|---|
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Change in Gut Microbiome Shannon Diversity Index
Periodo de tiempo: Baseline and Day 30
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Change in gut microbiome alpha diversity from baseline to Day 30, quantified using the Shannon diversity index derived from whole-genome shotgun metagenomic sequencing of stool samples. A single change value will be calculated for each participant as the Day 30 Shannon diversity index minus the baseline Shannon diversity index. Unit of Measure: Shannon diversity index |
Baseline and Day 30
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Medidas de resultado secundarias
Medida de resultado |
Medida Descripción |
Periodo de tiempo |
|---|---|---|
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Change in Stool Lipocalin-2 Concentration
Periodo de tiempo: Baseline and Day 30
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Change in stool lipocalin-2 concentration from baseline to Day 30, calculated as the Day 30 value minus the baseline value. Unit: ng/g stool |
Baseline and Day 30
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Change in Stool Calprotectin Concentration
Periodo de tiempo: Baseline and Day 30
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Change in stool calprotectin concentration from baseline to Day 30, calculated as the Day 30 value minus the baseline value. Unit: µg/g stool |
Baseline and Day 30
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Change in Serum Monocyte Chemoattractant Protein-1 Concentration
Periodo de tiempo: Baseline and Day 30
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Change in serum monocyte chemoattractant protein-1 (MCP-1) concentration from baseline to Day 30, calculated as the Day 30 value minus the baseline value. Unit: pg/mL |
Baseline and Day 30
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Change in Serum Interleukin-1 Beta Concentration
Periodo de tiempo: Baseline and Day 30
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Change in serum interleukin-1 beta (IL-1β) concentration from baseline to Day 30, calculated as the Day 30 value minus the baseline value. Unit: pg/mL |
Baseline and Day 30
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Change in Serum Tumor Necrosis Factor-Alpha Concentration
Periodo de tiempo: Baseline and Day 30
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Change in serum tumor necrosis factor-alpha (TNF-α) concentration from baseline to Day 30, calculated as the Day 30 value minus the baseline value. Unit: pg/mL |
Baseline and Day 30
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Change in Serum Interleukin-6 Concentration
Periodo de tiempo: Baseline and Day 30
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Change in serum interleukin-6 (IL-6) concentration from baseline to Day 30, calculated as the Day 30 value minus the baseline value. Unit: pg/mL |
Baseline and Day 30
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Change in Serum C-Reactive Protein Concentration
Periodo de tiempo: Baseline and Day 30
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Change in serum C-reactive protein (CRP) concentration from baseline to Day 30, calculated as the Day 30 value minus the baseline value. Unit: µg/mL |
Baseline and Day 30
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Change in Serum Zinc Concentration
Periodo de tiempo: Baseline and Day 30
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Change in serum zinc concentration from baseline to Day 30, calculated as the Day 30 value minus the baseline value. Unit: µg/dL |
Baseline and Day 30
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Change in Serum Iodine Concentration
Periodo de tiempo: Baseline and Day 30
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Change in serum iodine concentration from baseline to Day 30, calculated as the Day 30 value minus the baseline value. Unit: µg/dL |
Baseline and Day 30
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Change in Serum Magnesium Concentration
Periodo de tiempo: Baseline and Day 30
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Change in serum magnesium concentration from baseline to Day 30, calculated as the Day 30 value minus the baseline value. Unit: mg/dL |
Baseline and Day 30
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Change in Serum Folate Concentration
Periodo de tiempo: Baseline and Day 30
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Change in serum folate concentration from baseline to Day 30, calculated as the Day 30 value minus the baseline value. Unit: ng/mL |
Baseline and Day 30
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Change in Serum Vitamin D3 Concentration
Periodo de tiempo: Baseline and Day 30
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Change in serum vitamin D3 concentration from baseline to Day 30, calculated as the Day 30 value minus the baseline value. Unit: ng/mL |
Baseline and Day 30
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Change in Serum Vitamin B12 Concentration
Periodo de tiempo: Baseline and Day 30
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Change in serum vitamin B12 concentration from baseline to Day 30, calculated as the Day 30 value minus the baseline value. Unit: pg/mL |
Baseline and Day 30
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Gut Microbiome Beta Diversity Assessed by Bray-Curtis Dissimilarity
Periodo de tiempo: Baseline and Day 30
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Gut microbial community composition will be assessed at baseline and Day 30 using Bray-Curtis dissimilarity calculated from stool metagenomic sequencing data. Bray-Curtis dissimilarity will be used to evaluate differences in microbial community composition between intervention groups and study time points. Unit of Measure: Bray-Curtis dissimilarity |
Baseline and Day 30
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Change in EQ-5D Index Score in ADRD Participants
Periodo de tiempo: Baseline and Day 30
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Change in EuroQoL-5D (EQ-5D) health utility index score from baseline to Day 30 in participants with ADRD. Responses across the EQ-5D health dimensions will be converted to a single health utility index score according to the instrument scoring procedure. The outcome will be the Day 30 index score minus the baseline index score. Unit: EQ-5D index score |
Baseline and Day 30
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Change in Cohen-Mansfield Agitation Inventory Total Score
Periodo de tiempo: Baseline and Day 30
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Change in Cohen-Mansfield Agitation Inventory (CMAI) total score from baseline to Day 30 in participants with ADRD. Responses to individual CMAI items will be combined according to the instrument scoring procedure to generate one total agitation score at each time point. The outcome will be the Day 30 total score minus the baseline total score. Unit: CMAI total score |
Baseline and Day 30
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Change in Perceived Stress Scale Total Score in Caregivers
Periodo de tiempo: Baseline and Day 30
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Description: Change in Perceived Stress Scale (PSS) total score from baseline to Day 30 in caregivers. Individual PSS item responses will be combined according to the instrument scoring procedure to generate one total perceived stress score at each time point. The outcome will be the Day 30 total score minus the baseline total score. Unit: PSS total score |
Baseline and Day 30
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Change in State-Trait Anxiety Inventory State Anxiety Score
Periodo de tiempo: Baseline and Day 30
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Description: Change in the State-Trait Anxiety Inventory (STAI) State Anxiety score from baseline to Day 30 in caregivers. Responses to the State Anxiety items will be combined according to the instrument scoring procedure to generate one State Anxiety score at each time point. The outcome will be the Day 30 score minus the baseline score. Unit: STAI State Anxiety score |
Baseline and Day 30
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Change in State-Trait Anxiety Inventory Trait Anxiety Score
Periodo de tiempo: Baseline and Day 30
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Description: Change in the State-Trait Anxiety Inventory (STAI) Trait Anxiety score from baseline to Day 30 in caregivers. Responses to the Trait Anxiety items will be combined according to the instrument scoring procedure to generate one Trait Anxiety score at each time point. The outcome will be the Day 30 score minus the baseline score. Unit: STAI Trait Anxiety score |
Baseline and Day 30
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Otras medidas de resultado
Medida de resultado |
Medida Descripción |
Periodo de tiempo |
|---|---|---|
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Change in SF-36 Physical Component Summary Score
Periodo de tiempo: Baseline and Day 30
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Change in the Short Form-36 (SF-36) Physical Component Summary (PCS) score from baseline to Day 30 in caregivers. A single PCS summary score will be calculated at each time point, and the outcome will be the Day 30 PCS score minus the baseline PCS score. The SF-36 Mental Component Summary score is reported as a separate outcome measure. Unit: PCS score |
Baseline and Day 30
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Change in SF-36 Mental Component Summary Score
Periodo de tiempo: Baseline and Day 30
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Change in the Short Form-36 (SF-36) Mental Component Summary (MCS) score from baseline to Day 30 in caregivers. A single MCS summary score will be calculated at each time point, and the outcome will be the Day 30 MCS score minus the baseline MCS score. The SF-36 Physical Component Summary score is reported as a separate outcome measure. Unit: MCS score |
Baseline and Day 30
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Colaboradores e Investigadores
Patrocinador
Publicaciones y enlaces útiles
Publicaciones Generales
- Chaudhari DS, Jain S, Yata VK, Mishra SP, Kumar A, Fraser A, Kociolek J, Dangiolo M, Smith A, Golden A, Masternak MM, Holland P, Agronin M, White-Williams C, Arikawa AY, Labyak CA, Yadav H. Unique trans-kingdom microbiome structural and functional signatures predict cognitive decline in older adults. Geroscience. 2023 Oct;45(5):2819-2834. doi: 10.1007/s11357-023-00799-1. Epub 2023 May 22.
- Ullrich V. Cytochrome P450 and biological hydroxylation reactions. Top Curr Chem. 1979;83:67-104. doi: 10.1007/BFb0019663. No abstract available.
- Ekinci GN, Sanlier N. The relationship between nutrition and depression in the life process: A mini-review. Exp Gerontol. 2023 Feb;172:112072. doi: 10.1016/j.exger.2022.112072. Epub 2022 Dec 21.
- Covello C, Becherucci G, Di Vincenzo F, Del Gaudio A, Pizzoferrato M, Cammarota G, Gasbarrini A, Scaldaferri F, Mentella MC. Parenteral Nutrition, Inflammatory Bowel Disease, and Gut Barrier: An Intricate Plot. Nutrients. 2024 Jul 17;16(14):2288. doi: 10.3390/nu16142288.
- Roth-Walter F, Berni Canani R, O'Mahony L, Peroni D, Sokolowska M, Vassilopoulou E, Venter C. Nutrition in chronic inflammatory conditions: Bypassing the mucosal block for micronutrients. Allergy. 2024 Feb;79(2):353-383. doi: 10.1111/all.15972. Epub 2023 Dec 12.
- Yassine HN, Self W, Kerman BE, Santoni G, Navalpur Shanmugam N, Abdullah L, Golden LR, Fonteh AN, Harrington MG, Graff J, Gibson GE, Kalaria R, Luchsinger JA, Feldman HH, Swerdlow RH, Johnson LA, Albensi BC, Zlokovic BV, Tanzi R, Cunnane S, Samieri C, Scarmeas N, Bowman GL. Nutritional metabolism and cerebral bioenergetics in Alzheimer's disease and related dementias. Alzheimers Dement. 2023 Mar;19(3):1041-1066. doi: 10.1002/alz.12845. Epub 2022 Dec 8.
- Puga F, Wang D, Rafford M, Poe A, Pickering CEZ. The relationship between daily stressors, social support, depression and anxiety among dementia family caregivers: a micro-longitudinal study. Aging Ment Health. 2023 Jul-Aug;27(7):1291-1299. doi: 10.1080/13607863.2022.2116392. Epub 2022 Aug 29.
- Culberson JW, Kopel J, Sehar U, Reddy PH. Urgent needs of caregiving in ageing populations with Alzheimer's disease and other chronic conditions: Support our loved ones. Ageing Res Rev. 2023 Sep;90:102001. doi: 10.1016/j.arr.2023.102001. Epub 2023 Jul 5.
- Chen Y, Gao X, Sun F. Perceived Threat of Alzheimer's Disease and Related Dementias Among Chinese Family Caregivers of Older Adults with Cognitive Impairment. J Gerontol Soc Work. 2024 Oct;67(7):976-994. doi: 10.1080/01634372.2024.2339984. Epub 2024 Apr 8.
- Kivimaki M, Livingston G, Singh-Manoux A, Mars N, Lindbohm JV, Pentti J, Nyberg ST, Pirinen M, Anderson EL, Hingorani AD, Sipila PN. Estimating Dementia Risk Using Multifactorial Prediction Models. JAMA Netw Open. 2023 Jun 1;6(6):e2318132. doi: 10.1001/jamanetworkopen.2023.18132.
- Vogt NM, Kerby RL, Dill-McFarland KA, Harding SJ, Merluzzi AP, Johnson SC, Carlsson CM, Asthana S, Zetterberg H, Blennow K, Bendlin BB, Rey FE. Gut microbiome alterations in Alzheimer's disease. Sci Rep. 2017 Oct 19;7(1):13537. doi: 10.1038/s41598-017-13601-y.
- Zhao L, Guan L, Sun J, Li X. Serum levels of folate, vitamin B6, and vitamin B12 are associated with cognitive impairments in depression patients. Acta Neuropsychiatr. 2024 Feb;36(1):44-50. doi: 10.1017/neu.2023.41. Epub 2023 Aug 29.
- Nagpal R, Neth BJ, Wang S, Craft S, Yadav H. Modified Mediterranean-ketogenic diet modulates gut microbiome and short-chain fatty acids in association with Alzheimer's disease markers in subjects with mild cognitive impairment. EBioMedicine. 2019 Sep;47:529-542. doi: 10.1016/j.ebiom.2019.08.032. Epub 2019 Aug 30.
- Goto Y, Morita K, Suematsu M, Imaizumi T, Suzuki Y. Caregiver Burdens, Health Risks, Coping and Interventions among Caregivers of Dementia Patients: A Review of the Literature. Intern Med. 2023 Nov 15;62(22):3277-3282. doi: 10.2169/internalmedicine.0911-22. Epub 2023 Mar 1.
- Rawat P, Sehar U, Bisht J, Reddy AP, Reddy PH. Alzheimer's disease and Alzheimer's disease-related dementias in Hispanics: Identifying influential factors and supporting caregivers. Ageing Res Rev. 2024 Jan;93:102178. doi: 10.1016/j.arr.2023.102178. Epub 2023 Dec 27.
- Dhana K, Beck T, Desai P, Wilson RS, Evans DA, Rajan KB. Prevalence of Alzheimer's disease dementia in the 50 US states and 3142 counties: A population estimate using the 2020 bridged-race postcensal from the National Center for Health Statistics. Alzheimers Dement. 2023 Oct;19(10):4388-4395. doi: 10.1002/alz.13081. Epub 2023 Jul 17.
Fechas de registro del estudio
Fechas importantes del estudio
Inicio del estudio (Estimado)
Finalización primaria (Estimado)
Finalización del estudio (Estimado)
Fechas de registro del estudio
Enviado por primera vez
Primero enviado que cumplió con los criterios de control de calidad
Publicado por primera vez (Actual)
Actualizaciones de registros de estudio
Última actualización publicada (Actual)
Última actualización enviada que cumplió con los criterios de control de calidad
Última verificación
Más información
Términos relacionados con este estudio
Palabras clave
Términos MeSH relevantes adicionales
- Hormonas
- Hormonas, sustitutos hormonales y antagonistas hormonales
- Hormonas hipotalámicas
- Hormonas peptídicas
- Neuropéptidos
- Péptidos
- Aminoácidos, péptidos y proteínas
- Proteínas del tejido nervioso
- Proteínas
- Hormonas pituitarias
- Hormonas pituitarias, anterior
- Melanocortinas
- Pro-Opiomelanocortina
- Hormonas estimuladoras de melanocitos
Otros números de identificación del estudio
- Study007845
- 25A01 (Otro número de subvención/financiamiento: Florida Department of Health)
Plan de datos de participantes individuales (IPD)
¿Planea compartir datos de participantes individuales (IPD)?
Descripción del plan IPD
Información sobre medicamentos y dispositivos, documentos del estudio
Estudia un producto farmacéutico regulado por la FDA de EE. UU.
Estudia un producto de dispositivo regulado por la FDA de EE. UU.
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