Efficacy, Safety and Response Predictors of Adjuvant Astragalus for Cognition in Orthostatic Hypotension

Efficacy, Safety and Response Predictors of Adjuvant Astragalus for Cognition in Alzheimer Disease With Orthostatic Hypotension: an add-on, Assessor-blind, Pragmatic Randomized Controlled Trial

Background: This pragmatic clinical trial aims to determine the efficacy and safety of add-on Astragalus for cognition and non- cognition in patients with of mild to moderate Alzheimer's disease complicated with orthostatic hypotension in orthostatic hypotension, elucidate the underlying mechanisms, identify related response predictors, and explore effective drug components.

Methods: This is an add-on, assessor-blinded, parallel, pragmatic, randomized controlled trial. At least 66 adults with mild to moderate Alzheimer's disease (AD) and OH aged >30 years will be recruited. Participants will be randomized in a 1:1:1 ratio to receive 24 weeks of routine care or add-on low dose Astragalus or high dose Astragalus group. The primary efficacy outcome will be measured by the Alzheimer's Disease Assessment Scale-Cognitive Subscale, Chinese version. Secondary efficacy outcome assessment will include neuropsychological tests, blood pressure, plasma biomarkers, multimodal electroencephalograms, and neuroimaging. Safety outcome measures will include physical examinations, vital signs, electrocardiography, laboratory tests (such as hematologic and blood chemical tests), and adverse event records.

Inclusion Criteria:

The inclusion criteria will be as follows:

1. Male or female aged ≥50 years and ≤85 years
2. A decrease in systolic blood pressure of 20 mm Hg or a decrease in diastolic blood pressure of 10 mm Hg within 3 minutes after standing.
3. Memory loss for at least 6 months, with a progressive worsening trend
4. Patients with mild or moderate disease degree, that is, the total score of MMSE: 14 points < total score of MMSE <24 points, 0.5≤CDR≤2 points, and the total score of HAMD (24-item version) ≤20 points
5. Brain magnetic resonance imaging shows the degree of hippocampal atrophy is greater than or equal to grade 1
6. The modified Hachinski Ischemia Scale (m-HIS) score was < 4 points
7. The criteria described by the diagnostic and statistical manual of mental disorder-V for the diagnosis of dementia comply with the National Institute on Aging - Alzheimer's Association "Very likely AD" (National Institute of Aging-Alzheimer's Association, 2011).
8. There are no obvious positive signs in nervous system examination;
9. The subjects have the ability of reading, writing and communication, have a stable caregiver, accompany to attend the visit.
10. The basic treatment of AD before enrollment remained unchanged, and if long-term users needed to use it steadily for more than 4 weeks before randomization,the dose was kept as stable as possible during the study. Such drugs include: cholinesterase inhibitors and diamantine.

Exclusion Criteria:

The exclusion criteria will be as follows:

1. MRI showed significant focal lesions, including one of the following: a. There were more than 2 infarcts with a diameter greater than 2cm; b. Infarcts in key areas such as the thalamus, hippocampus, entorhinal cortex, parorhinal cortex, angular gyrus, cortex, and other subcortical gray matter nuclei; c. White matter lesion Fazekas Scale ≥3
2. Patients who have taken other Chinese medicine preparations in the past three months
3. Allergy or contraindication of astragalus
4. There are other neurological diseases that can cause brain dysfunction or cognitive impairment; Mental and neurological retardation is present; Presence of malignant tumor
5. The modified Hachinski Ischemia Scale (m-HIS) score was ≥ 4 points.
6. Patients who refuse or have MRI or EEG contraindications (pacemakers, coronary and peripheral arterial stents, Metal implants, claustrophobia, or severe visual or hearing impairment), refusing to draw blood
7. Pregnant or lactating patients;
8. Patients who have participated in other clinical studies within the past 3 months