Cognitive Impairment
Conditions
Brief summary
This pilot randomized, double-blind, crossover clinical trial will evaluate the effect of a synbiotic containing Lactobacillus acidophilus LA-5 and agave inulin on mild cognitive impairment (MCI) in adults aged 60-75 years attending the Defense Medical Specialties Unit. Forty participants with MCI will be randomized into two groups of 20 participants. The intervention will consist of daily administration of L. acidophilus LA-5 (4 × 10⁹ CFU), 7 g of agave inulin, and almond powder for 12 weeks, while the control group will receive almond powder as the vehicle. After a two-week washout period, participants will cross over to the alternate intervention for an additional 12 weeks. Cognitive function will be assessed using the Montreal Cognitive Assessment (MoCA), Memory Alteration Test (M@T), and Mini-Mental State Examination (MMSE). Secondary assessments will explore potential mechanisms of the microbiota-gut-brain axis by measuring fecal L. acidophilus LA-5 and butyrate, as well as serum BDNF and inflammatory biomarkers including IL-1β, IL-6, IL-10, and TNF-α. The study aims to determine whether synbiotic supplementation improves cognitive performance in older adults with MCI and whether these changes are accompanied by modifications in gut microbial activity, short-chain fatty acid production, neurotrophic signaling, and systemic inflammation.
Interventions
DIETARY_SUPPLEMENTSynbiotic (Lactobacillus acidophilus LA-5 and Agave Inulin) Intervention Type:
Participants will receive 2 g of Lactobacillus acidophilus LA-5 (4 × 10⁹ CFU), 7 g of agave inulin, and 20 g of almond powder dissolved in water, administered orally once daily for 12 weeks.
Sponsors
Anahuac University
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
60 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
* Adults aged 60 to 75 years. * Presence of mild cognitive impairment (MCI) determined by neuropsychological testing, meeting at least two of the following three established cutoff criteria: * Montreal Cognitive Assessment (MoCA): 19-26 points. * Memory Alteration Test (M@T): 28-37 points. * Mini-Mental State Examination (MMSE): 12-24 points. * Ability and willingness to provide written informed consent; consent may be provided by a family member or legal representative when necessary.
Exclusion criteria
* Previous diagnosis of severe cognitive impairment, Alzheimer disease, vascular dementia, or another neurodegenerative disorder affecting cognition. * History of cerebral ischemia, cerebrovascular events, traumatic brain injury, or advanced-stage renal disease. * Diagnosis of type 2 diabetes mellitus. * Diagnosed dysbiosis or inflammatory bowel disease, including ulcerative colitis or Crohn disease. * Use of antibiotics, laxatives, probiotics, or prebiotics within the 3 months prior to enrollment. * Habitual consumption of fermented foods or fiber-rich supplements, particularly fiber intake \>18 g/day. * Excessive alcohol consumption, defined as ≥2 alcoholic drinks per day, or history of alcohol dependence. * Chronic use of medications that may interfere with the microbiota-gut-brain axis, including immunosuppressants, antipsychotics, or corticosteroids. * Recent surgery within the previous 3 months or a planned medical intervention during the study period. * Known adverse reaction or hypersensitivity to any component of the synbiotic or to almond powder. * Uncontrolled chronic stress identified by clinical assessment. * Participation in intense physical activity or high-performance sports during the study.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in Montreal Cognitive Assessment (MoCA) Score | Baseline, end of the first intervention phase, and end of the second intervention phase. | The Montreal Cognitive Assessment (MoCA) will be used to assess changes in global cognitive function. The total score ranges from 0 to 30 points, with higher scores indicating better cognitive performance. A clinically meaningful improvement will be defined as an increase of at least 2 points from baseline, according to the study protocol. |
| Change in Memory Alteration Test (M@T) Score | : Baseline, end of the first intervention phase, and end of the second intervention phase. | he Memory Alteration Test (M@T) will be used to assess changes in memory function. The total score ranges from 0 to 50 points, with higher scores indicating better memory performance. The test evaluates orientation and several memory domains, including semantic, free-recall, and cued-recall components. A clinically meaningful improvement will be defined as an increase of at least 2 points from baseline. |
| Change in Mini-Mental State Examination (MMSE) Score | Baseline, end of the first intervention phase, and end of the second intervention phase. | The Mini-Mental State Examination (MMSE) will be used to assess changes in global cognitive function. The total score ranges from 0 to 30 points, with higher scores indicating better cognitive performance. A clinically meaningful improvement will be defined as an increase of at least 1.5 points from baseline, according to the study protocol. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in Serum Brain-Derived Neurotrophic Factor (BDNF) Concentration | Baseline, end of the first intervention phase, and end of the second intervention phase. | Serum brain-derived neurotrophic factor (BDNF) concentration will be quantified using enzyme-linked immunosorbent assay (ELISA). Results will be expressed in pg/mL. There is no predefined minimum or maximum score. Higher BDNF concentrations indicate greater circulating levels of this neurotrophic factor. |
| Change in Interleukin-1 Beta (IL-1β) Concentration | Baseline, end of the first intervention phase, and end of the second intervention phase. | IL-1β concentration will be quantified using ELISA and expressed in pg/mL. There is no predefined minimum or maximum score. Higher concentrations indicate greater levels of this pro-inflammatory cytokine. |
| Change in Interleukin-6 (IL-6) Concentration | Baseline, end of the first intervention phase, and end of the second intervention phase. | IL-6 concentration will be quantified using ELISA and expressed in pg/mL. There is no predefined minimum or maximum score. Higher concentrations indicate greater levels of this pro-inflammatory cytokine. |
| Change in Tumor Necrosis Factor Alpha (TNF-α) Concentration | Baseline, end of the first intervention phase, and end of the second intervention phase. | TNF-α concentration will be quantified using ELISA and expressed in pg/mL. There is no predefined minimum or maximum score. Higher concentrations indicate greater levels of this pro-inflammatory cytokine. |
| Change in Interleukin-10 (IL-10) Concentration | Baseline, end of the first intervention phase, and end of the second intervention phase. | IL-10 concentration will be quantified using ELISA and expressed in pg/mL. There is no predefined minimum or maximum score. Higher concentrations indicate greater levels of this anti-inflammatory cytokine. |
| Change in Fecal Butyrate Concentration | Baseline, end of the first intervention phase, and end of the second intervention phase. | Fecal butyrate concentration will be quantified using gas chromatography with flame ionization detection (GC-FID). Results will be expressed in mmol/g of fecal sample. There is no predefined minimum or maximum score. Higher concentrations indicate greater fecal butyrate production. |
| Change in Fecal Lactobacillus acidophilus LA-5 Count | Baseline, end of the first intervention phase, and end of the second intervention phase. | Fecal Lactobacillus acidophilus LA-5 will be quantified by colony-forming unit counts using selective MRS culture medium under anaerobic conditions. Results will be expressed as CFU/g of fecal sample. There is no predefined minimum or maximum score. Higher values indicate greater fecal abundance of L. acidophilus LA-5. |
Countries
Mexico
Contacts
CONTACTAntonio Ibarra, PhD
Outcome results
None listed