Glossary
This glossary breaks down key terms you’ll see in our coverage — what they mean, why they matter, and how they relate to Alzheimer’s care and research.
Allocation: A method used to assign participants to an arm of a clinical study. Allocation can be randomized and nonrandomized.
Amyloid Related Imaging Abnormalities (ARIA): ARIA is a broad term used to describe the side effects of anti-amyloid based therapies like Leqembi or Aduhelm. There are two types, ARIA-E, which refers to edema or brain swelling and ARIA-H which refers to microhemorrhages or brain bleeds. Most cases of ARIA are asymptomatic but researchers don’t yet know the long term impact of developing ARIA.
Beta-amyloid: This is a protein that is associated with Alzheimer’s disease when it forms into plaques. Beta-amyloid is thought to be an immune-modulating protein that also has antimicrobial properties. Think of it like a paperclip — a beta-amyloid monomer is one paperclip, an oligomer is a few paperclips, a protofibril is many paperclips, fibrils are longer versions of protofibrils, and a plaque occurs when the fibrils get jumbled up. Plaques begin to form more than a decade before the onset of Alzheimer’s symptoms, however not everyone who develops plaques develops Alzheimer’s disease.
Biologic: Drugs made of more complex molecules or cells, including vaccines and monoclonal antibodies. Biologics need to be synthesized or extracted from biological sources like blood plasma, bacteria, or cells.
Biomarker: A biological molecule or signal found in the body that correlates with health outcomes. In Alzheimer’s, there are protein-based biomarkers found in the blood and cerebrospinal fluid. There are also imaging biomarkers found in the brain. Some companies are also developing retinal and cognitive biomarkers.
Blinding: Blinding refers to whether participants or researchers know what intervention they receive during the study. In single-blinded studies, participants aren’t aware of their intervention group. In double-blinded studies, neither the participants nor the clinicians running the study know which intervention each participant receives. Blinding reduces the bias in the study.
Cholinesterase inhibitors (also known as acetylcholinesterase inhibitors): Drugs like Aricept (generic name: donepezil) and Exelon (generic name: rivastigmine)that help manage the symptoms of Alzheimer’s disease. These drugs prolong the effects of a signaling molecule in the brain called acetylcholine, which can temporarily improve cognitive symptoms.
Clinical research: Medical research that studies people to understand health and disease. The goal is to use the learnings from clinical research to improve people’s health.
Clinical trials: Research studies in which researchers assign participants to get one or more interventions in order to assess what happens in participants. Some interventions like diet or exercise might be readily available, while other interventions like drugs might still be experimental. This means that the only way to get some of these investigational drugs is to enroll in clinical trials.
Cross-over assignment study: This is a type of study where there are two groups of participants. The first group receives Treatment A for the first part of the study while the second group receives Treatment B. In the second phase of the study, the first group receives Treatment B and the second group receives Treatment A.
Eligibility criteria: Participants looking to join clinical research must meet certain eligibility criteria. Such criteria can revolve around people’s age, gender, whether or not they have a certain illness, disease or health condition, what their health history is composed of, whether or not they have been exposed to something that affects their health. Researchers use eligibility criteria to enroll the right participants they need in order to collect data around a specific research question.
Enrollment: The number of participants in a clinical study. The estimated enrollment is the number of participants researchers are targeting for the study.
Expanded access: A way for patients with serious diseases or conditions who cannot participate in a clinical trial to gain access to a medical product that has not been approved by the FDA for treatment. Expanded access is not available for all interventions being tested.
Factorial assignment study: This is a type of study where participants receive one or a combination of different therapies of interventions. For example, one study testing two drugs would split up participants into four equal groups receiving the following interventions:
- Drug 1 and Drug 2
- Drug 1 and placebo
- Placebo and Drug 2
- Placebo and Placebo
Funder: The organization that is responsible for paying the costs associated with carrying out a study. The funder can be the government of a country, drug manufacturers, medical centers, universities, or non-profit organizations.
Informed consent: A process used by researchers to communicate to potential and enrolled participants the potential risks and benefits of participating in a clinical trial.
Intervention model: The general design and process for assigning interventions to participants in a clinical study. Types of intervention models include: single group assignment, parallel assignment, cross-over assignment, and factorial assignment.
Microglia: The brain’s resident immune cells that gobble up pathogens and cell debris. Microglia can also eat and digest amyloid plaques. In Alzheimer’s, microglia cause excess inflammation and stop efficiently digesting amyloid plaques.
Monoclonal antibody: An antibody that is developed to target one specific part of a biological molecule. When these drugs bind to their target, they can turn a cell on or off, or they can stimulate an immune response. Drugs like Leqembi are monoclonal antibodies that bind to a specific component of beta-amyloid and stimulate an immune response when it binds, clearing the amyloid.
MRI scan: A medical imaging procedure that uses magnetic fields and radio waves to visualize structures in the body. In the context of Alzheimer’s, it can be used to assess brain shrinkage and spot swelling or bleeding that occurs as a side effect of drugs like Leqembi.
Observational study: Research studies in which researchers collect data from participants or look at data that was collected previously. In observational studies researchers do not assign participants to get an intervention. It is very difficult to determine cause and effect from observational studies but they can still provide important information about factors like diet or exercise that may impact health.
Parallel assignment study: This is a type of study where there are multiple interventions or treatments. It is common for clinical trials to have two parallel groups, a treatment and placebo group. Other studies may have more groups that test different interventions or doses of a drug.
Patient registry: An organized collection of data that serves as a record of information about patients’ medical conditions and/or treatments to better understand how a condition or treatment affects patients in the real world.
PET scan: A medical imaging procedure that involves injecting a radioactive marker into the blood to visualize specific proteins or metabolic processes in the body. In the context of Alzheimer’s, PET scans are used to assess the levels of beta-amyloid or tau in the brain. It can also be used to see whether the brain is able to use sugar efficiently — if it isn’t, then it’s a potential sign of Alzheimer’s.
Phase 1: A phase of research to describe clinical trials that focus on the safety of a drug.
Phase 2: A phase of research to describe clinical trials that gather preliminary data on a type of intervention’s effectiveness. Participants receiving the drug may be compared to similar participants receiving a different treatment that is usually a placebo. Some companies may run a combined Phase 1/Phase 2 study or a combined Phase 2/Phase 3 study.
Phase 3: A phase of research to describe clinical trials that gather more information about a drug’s safety and effectiveness by studying different populations and dosages.
Phase 4: A phase of research where the drug has already received FDA approval. Phase 4 includes postmarket requirement and commitment studies that are required of or agreed to by the study sponsor.
Placebo: When people participate in clinical trials, the participants and researchers might subconsciously expect that a treatment leads to improvement, affecting the outcome of the experiment. To lessen the impact of these expectations, researchers use a placebo — an inactive substance or treatment that looks the same as an active drug or intervention being studied. For medical procedures or brain stimulation devices, something similar called a sham procedure or sham device is used.
Preclinical research: Medical studies that are conducted in animal models or in cells grown in Petri dishes. Successful preclinical research is then tested in clinical studies.
Principal investigator (PI): The person who is leading the study and is responsible for the scientific and technical direction of the entire clinical study.
Randomized: Randomizing is the gold-standard allocation for clinical trials as it evens out the groups in the study. It can prevent a situation where all the healthier participants are assigned into one group, biasing the results of the study.
Single group assignment study: This is a type of study where every participant receives the same intervention or treatment.
Small molecule drug: Drugs made of small molecules packaged into pills or capsules like Aspirin, Tylenol or Aricept (generic name: donepezil). These drugs are easily synthesized in a lab.
Sponsor: The organization, such as a medical center or drug manufacturer, or person, such as a doctor, who initiates the study and has authority and control over the study.
Statistically significant: This is a scientific term that suggests the difference between two different experimental groups is not due to chance. However, just because there is a statistically significant difference between a treatment and intervention group doesn’t mean that the effects are large enough to be noticeable.
Study completion date: The date on which the last participant in a clinical study was examined or received an intervention/treatment.
Tau: Tau is a protein that stabilizes the cell’s microtubules which act as the highway, transporting nutrients and other molecules to where they’re needed. In Alzheimer’s, tau proteins start sticking to each other forming neurofibrillary tangles.
Type of intervention: A process that is the focus of a clinical study. Interventions are either investigational or already available and include drugs, medical devices, vaccines, dietary changes, and exercise.
Withdrawal: When a participant decides to leave the clinical study they were enrolled in. Participants can choose to withdraw at any time. Researchers might compare the numbers of people that withdraw from the placebo and the treatment group to help assess the severity of a treatment’s side effects.
