Candesartan's Effects on Alzheimer's Disease And Related Biomarkers

Hypotension is defined as blood pressure <100/40 mm Hg. Blood pressure was measured according to the American Heart Association guidelines with the subject in the sitting position and rested for 5 minutes. An appropriate cuff size (covering 60% of upper arm length and 80% of arm circumference) was used and correct cuff placement (1-2 inches above the brachial pulse on bare arm) was ensured.

Participants were asked to report any symptoms of hypotension (dizziness, weakness, fatigue and lightheadedness). All participants were given a telephone number to reach physician 24-hours per day to report symptoms they experience. The number of participants reporting symptoms of hypotension is reported here.

The number of participants with reported episodes hypotension as well as symptoms of hypotension.

The levels of creatinine were obtained from blood samples. Elevated serum creatinine is defined as levels >2.5 milligram per deciliter (mg/dL). Elevated serum creatinine is indicative of decreased renal function.

The levels of potassium were obtained from blood samples. Hyperkalemia is defined as potassium levels >5.9 milliequivalent per deciliter (meq/dL). Hyperkalemia is an indication of kidney dysfunction.

The number of participants who discontinued the study medication is presented here.

CSF total tau (t-tau) levels were analyzed from CSF samples obtained via lumbar puncture. Normal values for t-tau are < 450 pg/ml. Elevated levels of t-tau indicate worsening disease.

CSF levels of p-tau181 were analyzed from CSF samples obtained via lumbar puncture. P-tau181 is a biomarker that is elevated in persons with Alzheimer's disease. Higher values indicate worsening disease.

CSF Aβ42 levels were analyzed from CSF samples obtained via lumbar puncture. Aβ42 is a biomarker for Alzheimer's disease and lower values indicate worsening disease and an increased accumulation of amyloid in the brain.

CSF Aβ40 levels were analyzed from CSF samples obtained via lumbar puncture. Lower values indicate worsening disease and an increased brain accumulation of amyloid.

CSF Aβ42/Aβ40 levels were analyzed from CSF samples obtained via lumbar puncture. A lower ratio indicates worsening disease.

Arterial stiffness was assessed by Pulse Wave Velocity (PWV). PWV is calculated as PWV=distance (d)/time (t) and the unit of measure is reported as meters per second (m/s). Lower values indicate a preferable measurement of arterial stiffness.

Arterial stiffness was assessed by Augmentation Index (AI). The AI is a ratio measure of augmentation of central arterial pressure reflected in a pulse wave; the value is multiplied by 100 to provide a percentage. AI increases with age and is higher in persons with cardiovascular disease states. A lower value indicates a preferable state of arterial stiffness.

Structural MRI images were acquired in order to assess hippocampal volume. Decreased hippocampal volume suggests neurodegenerative changes

Cerebrovascular reactivity (CVR) is assessed with blood oxygenation level-dependent (BOLD) MRI. Vasoreactivity (VR) is the degree of change in BOLD signal relative to change in end tidal CO2. CVR is an indicator of microvascular function (higher indicates better function)

In-vivo amyloid imaging with positron emission tomography (PET) was conducted after intravenous administration of 15±1.5 millicurie (mCi) of the radiotracer (11)C-PiB. SUVR is a ratio of PET uptake measured in the brain region of interest and a disease free reference region. A higher SUVR is an indication of increased PET radiotracer uptake and worsening disease.

In-vivo tau-PET imaging was conducted using the radiotracer [18F]T807. SUVR is a ratio of PET uptake measured in the brain region of interest and a disease free reference region. A higher SUVR is an indication of increased PET radiotracer uptake and worsening disease.

The CDR rates each of the six general domains involving memory, orientation, judgment and problem-solving, community affairs, home and hobbies, and personal care. An overall score, ranging from 0 to 3, can be calculated. A score of 0 = normal, 0.5 = very mild dementia, 1 = mild dementia, 2 = moderate dementia, and 3 = severe dementia.

The EXAMINER toolbox battery includes 11 tasks that generate 15 primary variables. Within this set, the EXAMINER includes working memory, inhibition, set shifting, and fluency. The parts of EXAMINER that were used for this study include: Flanker task (inhibition) which involves responding to a central stimulus while ignoring flanking stimuli that are either compatible or incompatible with the central stimulus; Set-shifting, a measure of mental flexibility; Spatial 1-Back test assesses spatial working memory; Dot Counting test assesses verbal working memory; Verbal Fluency tested using a List Generation test which require the participant to generate words beginning with a specific letter, and category fluency in which the participant generates words from a specified category (e.g., animals, fruits). A composite score is calculated where scores range from -1 to +1 and higher are reflective of better executive function.

The Hopkins Verbal Learning Test (HVLT) is used to assess memory domains. Participants are read a list of 12 words and are asked to recall as many as they can remember. This is repeated for 3 trials followed by a 20 minute delay, and then participants are asked to recall as many words as they can. The delayed recall score ranges from 0 to 12 and higher scores indicate better memory.

The Trail Making Test assesses executive function. In Part B of the TMT participants connect circles labeled with letters and numbers, in ascending order. The score is the amount of time it takes for the participant to complete the task. The average time is 75 seconds and times greater than 273 seconds indicate a deficit with executive function.

In Parts A and B of the TMT, participants connect circles labeled with numbers, in ascending order. The score is the amount of time (in seconds) it takes for the participant to complete the task. The TMT Part A score reflects visuoperceptual abilities, and subtracting the score for Part A from the score from Part B (Part B-A, in seconds) provides a more accurate assessment of executive function. A lower score indicates greater executive function.