DECEMBER 2015/JANUARY 2016 BY MARISA COHEN Dementia 101: Know the Dioerent Types of Dementia Not all dementia is Alzheimer's disease. Knowing the dioerence aoects planning, management, and prognosis. Our primer breaks down the four most common types, as well as four not-so-common ones. Forgetting a name, misplacing keys, becoming momentarily confused—these can be byproducts of normal aging or the early symptoms of dementia. If it's normal aging, the names will be recalled, the keys will be found, and the confusion will lift. But for the 14 percent of Americans over age 70 who have some type of dementia, those names may never come back, and the memory loss and confusion become so debilitating that daily tasks like driving, shopping, and paying bills become increasingly difficult. As Americans continue to live longer, dementia is poised to become the biggest health challenge of the next few decades. The US Centers for Disease Control and Prevention (CDC) expects the number of people living with Alzheimer's disease, the leading cause of dementia, to more than double from 5 million to 14 million by 2050. Still, about half of all cases of Alzheimer's—not to mention other types of debilitating brain disease, including non-Alzheimer's dementia—go undiagnosed, says John C. Morris, MD, FAAN, director of the Knight Alzheimer's Disease ILLUSTRATION BY BRIAN Research Center at Washington University in St. Louis. STAUFFER It's Be}er to Know Because no cure exists for most types of dementia, many patients and their families hesitate to have their suspicions confirmed. But experts recommend speaking to a neurologist as soon as memory or behavior problems occur. "I've found that people deal with disease better if they have more information about it," says Paul Barton Rosenberg, MD, associate director of the Memory and Alzheimer's Treatment Center at Johns Hopkins University. "Getting an accurate prognosis, which is different for different types of dementia, helps patients and caregivers plan better and allays their anxiety." And the earlier people get a diagnosis, the more likely they are to be eligible for research trials, Dr. Rosenberg says. (For more information about enrolling in trials, check out the Alzheimer's Association TrialMatch tool.) Follow this primer to understand the differences between Alzheimer's disease and other dementias, and to learn ways to manage the symptoms. Alzheimer's Disease CAUSES: The brain changes characteristic of Alzheimer's disease, which affects between 60 and 80 percent of all people with dementia, usually start years before any symptoms appear, when protein deposits start to form in the brain. Plaques, which are made up of a protein called beta-amyloid, clog the spaces between nerve cells; a little later in the process, tangles—twisted fibers of the tau protein— accumulate inside the cells. Both interfere with the ability of neurons to send and receive information and eventually cause brain cells to die. "Clinical problems typically begin with hippocampus-related short-term memory and learning, but gradually involve temporal, frontal, and occipital lobe functions, including language, executive function, and vision," says Dena Dubal, MD, PhD, an assistant professor of neurology and an endowed chair of aging and neurodegenerative disease at the University of California, San Francisco. In Alzheimer's disease, the cortex, the outer layer of the cerebrum, shrinks, and the ventricles, hollow cavities that hold cerebrospinal fluid, become enlarged and misshapen. ILLUSTRATIONS BY BIODIGITAL SYMPTOMS: The most noticeable early symptom is short-term memory loss. People may remember childhood stories but will forget conversations that happened five minutes earlier. They may also have difficulty retaining new information, asking the same questions repeatedly. Depression and apathy are also common at this point, as is confusion about dates and times. As the disease progresses, people start using poor judgment, have trouble communicating, or are confused and disoriented. By the end, people have trouble speaking, following a conversation, swallowing, and walking. CURRENT TREATMENTS: The disease cannot be stopped or reversed, but the US Food and Drug Administration (FDA) has approved two types of medications to treat symptoms: acetylcholinesterase inhibitors, which inhibit the breakdown of acetylcholine, a brain chemical involved in learning and memory; and memantine, which blocks the activity of the neurotransmitter glutamate, which at high levels can destroy nerve cells. Acetylcholinesterase inhibitors are often prescribed in the earlier stages of the disease and include donepezil (Aricept), galantamine (Razadyne), and rivastigmine (Exelon). Memantine (Namenda) is used more in the later stages and may help with language, attention, and the ability to perform simple tasks. However, these drugs work for only about half the people who take them, and their effects last only six to 12 months. NEW TREATMENTS: Eli Lilly's phase 3 trials of a drug called solanezumab show that this antibody may slow the progress of very mild Alzheimer's dementia by binding the beta-amyloid protein and helping the body flush it out before it can develop into sticky plaque, although more research is needed. Trials are also underway with BACE inhibitors, which block beta-secretase 1, an enzyme that contributes to the production of beta-amyloid, and with other antibodies designed to clear accumulated toxic proteins from the brain. ONGOING RESEARCH: Breakthroughs in genetics, biomarkers, and brain imaging should soon make it easier to diagnose conditions like Alzheimer's in the earliest stages, even before symptoms begin, when these drugs may be most effective. Scientists are looking at ways to detect the earliest hints of Alzheimer's by measuring the level of tau and beta-amyloid proteins in the blood, urine, cerebrospinal fluid, and even in the lens and retina of the eye. They are also examining how positron emission tomography (PET) scans might be used to analyze brain volume and glucose levels to detect early changes. Meanwhile, geneticists are trying to identify genes that indicate a predisposition to Alzheimer's. AGE OF FIRST SYMPTOMS: Although changes in the brain can begin decades earlier, in the stage known as pre-clinical Alzheimer's disease, the majority of people don't exhibit symptoms until their mid-60s or later. "A small subgroup of people, less than 1 percent of all Alzheimer's patients, inherit a genetic mutation that causes the disease. For them, the disease can start in their 50s, 40s, 30s, and, rarely, in their 20s," says Dr. Morris. By age 85, there is almost a one-in-three chance that any given adult will have Alzheimer's, according to research from the Rush Institute for Healthy Aging. PROGNOSIS: The average person with Alzheimer's disease lives about eight years past his or her diagnosis. That time can be shortened to a few years or lengthened to as many as 20, depending on how old the person is at diagnosis and other health conditions. ASSOCIATION: Alzheimer's Association Lewy Body Dementia CAUSE: Described by Dr. Rosenberg as "a cross between Alzheimer's disease and Parkinson's disease," this type of dementia occurs when protein deposits called Lewy bodies accumulate in nerve cells in the areas of the brain responsible for memory, motor control, and thinking. (When the Lewy bodies attack the brainstem first, causing stiffness, rigid muscles, and difficulty walking, the condition is diagnosed as Parkinson's disease.) "As the disease progresses and the protein bodies spread across the brain, people with Lewy body dementia begin to have Parkinsonian symptoms. And the majority of people with Parkinson's disease develop dementia," Dr. Dubal explains. Shrinkage occurs in the temporal and parietal lobes, which process sensory information; in the midbrain, which integrates sensory information with muscle movement; and in the cingulate gyrus, which regulates emotion and pain. BIODIGITAL SYMPTOMS: Visual hallucinations are common in people with Lewy body dementia. They may start talking to someone who isn't there or see specific images of animals or objects. Their moods and awareness may fluctuate rapidly. "A patient may seem coherent one moment and then be staring into space the next," says Dr. Dubal. People may also have sleep disturbances such as acting out dreams at night, says Jennifer Molano, MD, an assistant professor of neurology at the University of Cincinnati Academic Health Center. As the disease progresses, the physical symptoms of Parkinson's, such as rigid muscles and stiffness, can appear. TREATMENT: No medications have been developed specifically for Lewy body dementia, but neurologists often treat memory problems with the same acetylcholinesterase inhibitors used for Alzheimer's. They treat movement difficulties with levodopa, a standard treatment for Parkinson's disease. For people with severe, debilitating hallucinations, neurologists may prescribe antipsychotics —with caution. Antipsychotics can make cognitive symptoms worse, cause heavy sedation, or increase Parkinson's-like symptoms. In addition, the FDA has warned that both typical and atypical antipsychotics increase the risk of death in elderly people with dementia. Typical antipsychotics, including chlorpromazine (Thorazine) and haloperidol (Haldol), are not recommended for people with Lewy body dementia. Newer atypical antipsychotics, such as quetiapine (Seroquel) and clozapine (Clozaril), may be prescribed at low doses, but should be monitored very closely. AGE OF FIRST SYMPTOMS: Symptoms usually appear after age 60; the disease is more common in men than in women. PROGNOSIS: Survival is about eight years after diagnosis. ASSOCIATION: Lewy Body Dementia Association Vascular Dementias CAUSE: Vascular dementias include a number of disorders in which cerebrovascular disease prevents proper blood flow to the brain, depriving brain cells of oxygen and nutrients, which lead to cognitive decline. Damage to blood vessels can occur as a result of a major stroke, a series of tiny strokes, or chronic untreated high blood pressure. Damaged blood vessels can rupture, causing blood clots (inset) and a series of small strokes.