Related Experiment Video
Updated: Jan 3, 2026
The 4 Mountains Test: A Short Test of Spatial Memory with High Sensitivity for the Diagnosis of Pre-dementia Alzheimer's Disease
Published on: October 13, 2016
Minocycline at 2 Different Dosages vs Placebo for Patients With Mild Alzheimer Disease: A Randomized Clinical Trial
Robert Howard1, Olga Zubko2, Rosie Bradley3
1Division of Psychiatry, University College London, London, United Kingdom.
Importance:
There are no disease-modifying treatments for Alzheimer disease (AD), the most common cause of dementia. Minocycline is anti-inflammatory, protects against the toxic effects of β-amyloid in vitro and in animal models of AD, and is a credible repurposed treatment candidate.
Objective:
To determine whether 24 months of minocycline treatment can modify cognitive and functional decline in patients with mild AD.
Design, Setting, And Participants:
Participants were recruited into a double-blind randomized clinical trial from May 23, 2014, to April 14, 2016, with 24 months of treatment and follow-up. This multicenter study in England and Scotland involved 32 National Health Service memory clinics within secondary specialist services for people with dementia. From 886 screened patients, 554 patients with a diagnosis of mild AD (Standardised Mini-Mental State Examination [sMMSE] score ≥24) were randomized.
Interventions:
Participants were randomly allocated 1:1:1 in a semifactorial design to receive minocycline (400 mg/d or 200 mg/d) or placebo for 24 months.
Main Outcomes And Measures:
Primary outcome measures were decrease in sMMSE score and Bristol Activities of Daily Living Scale (BADLS), analyzed by intention-to-treat repeated-measures regression.
Results:
Of 544 eligible participants (241 women and 303 men), the mean (SD) age was 74.3 (8.2) years, and the mean (SD) sMMSE score was 26.4 (1.9). Fewer participants completed 400-mg minocycline hydrochloride treatment (28.8% [53 of 184]) than 200-mg minocycline treatment (61.9% [112 of 181]) or placebo (63.7% [114 of 179]; P < .001), mainly because of gastrointestinal symptoms (42 in the 400-mg group, 15 in the 200-mg group, and 10 in the placebo group; P < .001), dermatologic adverse effects (10 in the 400-mg group, 5 in the 200-mg group, and 1 in the placebo group; P = .02), and dizziness (14 in the 400-mg group, 3 in the 200-mg group, and 1 in the placebo group; P = .01). Assessment rates were lower in the 400-mg group: 68.4% (119 of 174 expected) for sMMSE at 24 months compared with 81.8% (144 of 176) for the 200-mg group and 83.8% (140 of 167) for the placebo group. Decrease in sMMSE scores over 24 months in the combined minocycline group was similar to that in the placebo group (4.1 vs 4.3 points). The combined minocycline group had mean sMMSE scores 0.1 points higher than the placebo group (95% CI, -1.1 to 1.2; P = .90). The decrease in mean sMMSE scores was less in the 400-mg group than in the 200-mg group (3.3 vs 4.7 points; treatment effect = 1.2; 95% CI, -0.1 to 2.5; P = .08). Worsening of BADLS scores over 24 months was similar in all groups: 5.7 in the 400-mg group, 6.6 in the 200-mg group, and 6.2 in the placebo groups (treatment effect for minocycline vs placebo = -0.53; 95% CI, -2.4 to 1.3; P = .57; treatment effect for 400 mg vs 200 mg of minocycline = -0.31; 95% CI, -0.2 to 1.8; P = .77). Results were similar in different patient subgroups and in sensitivity analyses adjusting for missing data.
Conclusions And Relevance:
Minocycline did not delay the progress of cognitive or functional impairment in people with mild AD during a 2-year period. This study also found that 400 mg of minocycline is poorly tolerated in this population.
Trial Registration:
isrctn.org Identifier: ISRCTN16105064.
Insights
Minocycline did not slow cognitive or functional decline in mild Alzheimer disease (AD) over two years. The 400 mg dose was poorly tolerated, with more side effects than placebo.
Area of Science:
- Neurology
- Clinical Trials
- Pharmacology
Background:
- Alzheimer disease (AD) is the most common cause of dementia with no disease-modifying treatments.
- Minocycline, an anti-inflammatory drug, has shown neuroprotective effects in preclinical AD models.
- Repurposing minocycline is a potential strategy for AD treatment.
Purpose of the Study:
- To evaluate the efficacy of 24-month minocycline treatment in modifying cognitive and functional decline in mild AD patients.
- To assess the safety and tolerability of different minocycline dosages.
Main Methods:
- A double-blind, randomized, placebo-controlled clinical trial involving 554 patients with mild AD.
- Participants received minocycline (400 mg/d or 200 mg/d) or placebo for 24 months.
- Cognitive decline was measured by the Standardised Mini-Mental State Examination (sMMSE) and functional decline by the Bristol Activities of Daily Living Scale (BADLS).
Main Results:
- Minocycline treatment did not significantly alter the rate of cognitive or functional decline compared to placebo.
- The 400 mg/d dose of minocycline was associated with significantly lower completion rates due to adverse events, including gastrointestinal and dermatologic issues.
- No significant differences in BADLS score worsening were observed across the treatment groups.
Conclusions:
- Minocycline does not appear to be an effective disease-modifying treatment for mild Alzheimer disease.
- Higher doses of minocycline (400 mg/d) exhibit poor tolerability in this patient population.
- Further research may explore different therapeutic targets or drug delivery methods for AD.
More Related Videos
08:43Application of Granger Causality Analysis of the Directed Functional Connection in Alzheimer's Disease and Mild Cognitive Impairment
Published on: August 7, 2017
05:54Author Spotlight: Exploring Acupuncture in Alzheimer's Research from Thread-Embedding Techniques to Clinical Trials
Published on: May 10, 2024
Related Concept Videos
01:22Alzheimer's Disease: Treatment
01:26Alzheimer's Disease: Overview
The clinical diagnosis of AD hinges on the presence of memory and other cognitive impairments. Biomarkers, such as changes in Aβ...
01:15Drug Dosing: Geriatric Patients
01:01Dosage Regimen: Fixed Dose
Fixed-dose regimens can be used for various routes of administration, including intravenous (IV) injections and oral medications. For IV administration, a predetermined amount of the drug is...