What is AD? Alzheimer’s disease is an irreversible, progressive brain disease that slowly destroys memory and thinking skills.Although the risk of developing AD increases with age – inmost people with AD, symptoms first appear after age 60 –AD is not a part of normal aging. It is caused by a fataldisease that affects the brain.
What is AD?AD Statistics….• AD is the most common cause of dementia among people age 65 and older.• Scientists estimate that around 4.5 million people now have AD. • By 2050, 13.2 million older• For every 5-year age Americans are expected to have group beyond 65, the AD if the current numbers hold percentage of people with AD doubles. and no preventive treatments become available.
What is AD? Where are people with AD cared for? • home • assisted living facilities (those in the early stages) • nursing homes (special care units) • The national cost of caring for people with AD is about $100 billion every year.
Inside the Human BrainTo understandAlzheimer’s disease,it’s important toknow a bit about thebrain… The Brain’s Vital Statistics• Adult weight: about 3 pounds• Adult size: a medium cauliflower• Number of neurons: 100,000,000,000 (100 billion)• Number of synapses (the gap between neurons): 100,000,000,000,000 (100 trillion)
Inside the Human Brain The Three Main Players1. Cerebral Hemispheres – where sensory information received from the outside world is processed; this part of the brain controls voluntary movement and regulates conscious thought and mental activity: • accounts for 85% of brain’s weight • consists of two hemispheres connected by the corpus callosum • is covered by an outer layer called the cerebral cortex
Inside the Human Brain The Three Main Players2. Cerebellum – in charge of balance and coordination: • takes up about 10% of brain • consists of two hemispheres • receives information from eyes, ears, and muscles and joints about body’s movements and position
Inside the Human Brain The Three Main Players3. Brain Stem – connects the spinal cord with the brain • relays and receives messages to and from muscles, skin, and other organs • controls automatic functions such as heart rate, blood pressure, and breathing Slide 11
Inside the Human Brain Other Crucial Parts• Hippocampus: where short-term memories are converted to long-term memories• Thalamus: receives sensory and limbic information and sends to cerebral cortex• Hypothalamus: monitors certain activities and controls body’s internal clock• Limbic system: controls emotions and instinctive behavior (includes the hippocampus and parts of the cortex) Slide 12
Inside the Human Brain The Brain in ActionHearing Words Speaking Words Seeing Words Thinking about Words Different mental activities take place in different parts of the brain. Positron emission tomography (PET) scans can measure this activity. Chemicals tagged with a tracer “light up” activated regions shown in red and yellow. Slide 13
Inside the Human Brain Neurons• The brain has billions of neurons, each with an axon and many dendrites.• To stay healthy, neurons must communicate with each other, carry out metabolism, and repair themselves.• AD disrupts all three of these essential jobs. Slide 14
AD and the Brain Plaques and Tangles: The Hallmarks of ADThe brains of people with AD have an abundance of twoabnormal structures: • beta-amyloid plaques, which are dense deposits of protein and cellular material that accumulate outside and around nerve cells • neurofibrillary tangles, which are twisted fibers that build up inside the nerve cell An actual AD plaque An actual AD tangle Slide 16
AD and the Brain Beta-amyloid Plaques1. Amyloid precursor protein (APP) is the precursor to amyloid plaque. 1. APP sticks through the neuron membrane. 2. Enzymes cut the APP into fragments of protein, including beta-amyloid.2. 3. Beta-amyloid fragments come together in clumps to form plaques. In AD, many of these clumps form, disrupting the work of neurons. This3. affects the hippocampus and other areas of the cerebral cortex. Slide 17
AD and the Brain Neurofibrillary TanglesNeurons have an internal support structure partly made up ofmicrotubules. A protein called tau helps stabilize microtubules. In AD,tau changes, causing microtubules to collapse, and tau proteins clumptogether to form neurofibrillary tangles. Slide 18
AD and the Brain The Changing Brain in Alzheimer’s Disease No one knows what causes AD to begin, but we do know a lot about what happens in the brain once AD takes hold. Pet Scan of Normal Brain Pet Scan of Alzheimer’s Disease Brain Slide 19
AD and the Brain Preclinical AD • Signs of AD are first noticed in the entorhinal cortex, then proceed to the hippocampus. • Affected regions begin to shrink as nerve cells die. • Changes can begin 10-20 years before symptoms appear. • Memory loss is the first sign of AD. Slide 20
AD and the Brain • AD spreads through the brain. TheMild to Moderate AD cerebral cortex begins to shrink as more and more neurons stop working and die. • Mild AD signs can include memory loss, confusion, trouble handling money, poor judgment, mood changes, and increased anxiety. • Moderate AD signs can include increased memory loss and confusion, problems recognizing people, difficulty with language and thoughts, restlessness, agitation, wandering, and repetitive statements. Slide 21
AD and the Brain Severe AD • In severe AD, extreme shrinkage occurs in the brain. Patients are completely dependent on others for care. • Symptoms can include weight loss, seizures, skin infections, groaning, moaning, or grunting, increased sleeping, loss of bladder and bowel control. • Death usually occurs from aspiration pneumonia or other infections. Caregivers can turn to a hospice for help and palliative care. Slide 22
Clinical Manifestationsbeginning with memory impairment and spreading tolanguage and visuospatial deficits. Yet, approximately 20%of patients with AD present with nonmemory complaintssuch as word-finding, organizational, or navigationaldifficulty. In the early stages of the disease, the memoryloss may go unrecognized or be ascribed to benignforgetfulness. Once the memory loss becomes noticeable tothe patient and spouse and falls 1.5 standard deviationsbelow normal on standardized memory tests, the term MCIis applied. This construct provides useful prognosticinformation, because approximately 50% of patients withMCI (roughly 12% per year) will progress to AD over 4years.
In the late stages of the disease, some persons remainambulatory but wander aimlessly. Loss of judgment andreasoning is inevitable. Delusions are common and usuallysimple, with common themes of theft, infidelity, ormisidentification. Approximately 10% of AD patientsdevelop Capgras syndrome, believing that a caregiver hasbeen replaced by an impostor. In contrast to DLB, whereCapgras syndrome is an early feature, in AD this syndromeemerges later. Loss of inhibitions and aggression may occurand alternate with passivity and withdrawal. Sleep-wakepatterns are disrupted, and nighttime wandering becomesdisturbing to the household.
AD Research: theSearch for CausesAD develops • AD develops when genetic, lifestyle, and environmental factors work together to cause the disease process to start. • In recent years, scientists have discovered genetic links to AD. They are also investigating other factors that may play a role in causing AD. NIA-funded Alzheimer’s Disease Centers (ADCs) across the country are leading the research efforts looking into causes, diagnosis, and treatment of AD. Slide 24
AD Research: the Search for CausesGenetic StudiesThe two main types of AD areearly-onset and late-onset:• Early-onset AD is rare, usually affecting people aged 30 to 60 and usually running in families. Researchers have identified mutations in three genes that cause early-onset AD.• Late-onset AD is more common. It usually affects people over age 65. Researchers have identified a gene that produces a protein called apolipoprotein E (ApoE). Scientists believe this protein is involved in the formation of beta-amyloid plaques. Slide 25
AD Research: the Search for CausesLate-onset ADGenetics Study• Partnership between the NIA and the Alzheimer’s Association• Need to recruit a total of 1,000 families to find the remaining late-onset risk factor genes• 2 or more living siblings with AD• One other living family member with or without AD• Contact: e-mail: email@example.com or Website: www.ncrad.org Slide 26
AD Research: the Search for Causes Studies at the Cellular and Molecular Level • Oxidative damage from free radical molecules can injure neurons.• Homocysteine, an amino acid, is a risk factor for heart disease. A study shows that an elevated level of homocysteine is associated with increased risk of AD.• Scientists are also looking at inflammation in certain regions of the brain and strokes as risk factors for AD. Slide 27
AD Research: the Search for CausesEpidemiologic Studies Scientists examine characteristics, lifestyles, and disease rates of groups of people to gather clues about possible causes of AD. The NIA is currently funding epidemiologic studies in a variety of different groups. Two of the studies focus on religious communities. Researchers conduct yearly exams of physical and mental status, and studies of donated brains at autopsy. Some early results indicate: • Mentally stimulating activity protects the brain in some ways. • In early life, higher skills in grammar and density of ideas are associated with protection against AD in late life. Slide 28
AD Research: Diagnosing AD Experienced physicians in specialized AD centers can now diagnose AD with up to 90 percent accuracy. Early diagnosis has advantages: • Doctors can rule out other conditions that may cause dementia. • If it is AD, families have more time to plan for the future. • Treatments can start earlier, when they may be more effective. • It helps scientists learn more about the causes and development of AD. Slide 29
AD Research: Diagnosing ADPhysicians today use a numberof tools to diagnose AD:• a detailed patient history• information from family and friends• physical and neurological exams and lab tests• neuropsychological tests• imaging tools such as CT scan, or magnetic resonance imaging (MRI). PET scans are used primarily for research purposes Slide 30
Donepezil (target dose, 10 mg daily), rivastigmine(target dose, 6 mg twice daily or 9.5-mg patchdaily), galantamine (target dose 24 mg daily,extended-release), memantine (target dose, 10 mgtwice daily), and tacrine are the drugs presentlyapproved by the Food and Drug Administration(FDA) for treatment of AD.
AD Research: Clinical Trials Clinical trials are the primary way that researchers find out if a promising treatment is safe and effective. • Trials examine approved drugs to see if they can be used for other purposes, or look at experimental drugs. • Participating in a trial means regular contact with the study team, who can provide state-of- the-art AD care. Slide 31
AD Research: the Search for TreatmentsDrugs used to treat mild to moderate AD symptoms include: • Aricept • Exelon • ReminylAn additional drug, Namenda, has been approved to treat symptoms ofmoderate to severe AD. These drugs can help improve some patients’abilities to carry out activities up to a year or so, but they do not stop orreverse AD.Scientists are also studying agents that someday may beuseful in preventing AD. For example, they haveexperimented with a vaccine against AD. Although thefirst clinical trial was stopped due to side effects in someparticipants, valuable information was gathered. Slide 32
AD Research: the Search for New Treatments Researchers also are looking at other treatments, including: • cholesterol-lowering drugs called statins • anti-oxidants (vitamins) and folic acid • anti-inflammatory drugs • substances that prevent formation of beta-amyloid plaques • nerve growth factor to keep neurons healthy Slide 33
AD Research: New NIA StudyThe NIA is launching a new researchpartnership, called the Neuroimaging andBiomarkers of AD Initiative, to study howthe brain changes in Mild CognitiveImpairment (MCI) and AD. • Using MRIs and PET scans conducted at regular intervals, researchers hope to learn precisely when and where in the brain problems occur. • Researchers will also examine blood samples to check for higher levels of abnormal substances that could be considered “biomarkers” of AD. Slide 34
AD Research: Managing Symptoms Between 70 to 90% of people with AD eventually develop behavioral symptoms, including sleeplessness, wandering and pacing, aggression, agitation, anger, depression, and hallucinations and delusions. Experts suggest these general coping strategies for managing difficult behaviors: • Stay calm and be understanding. • Be patient and flexible. Don’t argue or try to convince. • Acknowledge requests and respond to them. • Try not to take behaviors personally. Remember: it’s the disease talking, not your loved one.Experts encourage caregivers to try non-medical coping strategiesfirst. However, medical treatment is often available if the behaviorhas become too difficult to handle. Researchers continue to look atboth non-medical and medical ways to help caregivers. Slide 35
Support for Caregivers Who are the AD Caregivers? • Spouses – the largest group. Most are older with their own health problems. • Daughters – the second largest group. Called the “sandwich generation,” many are married and raising children of their own. Children may need extra support if a parent’s attention is focused on caregiving. • Grandchildren – may become major helpers. • Daughters-in-law – the third largest group. • Sons – often focus on the financial, legal, and business aspects of caregiving. • Brothers and Sisters – many are older with their own health problems. • Other – friends, neighbors, members of the faith community. Slide 37
Support for CaregiversDemands of CaregivingAD takes a huge physical andemotional toll. Caregivers mustdeal with changes in a loved one’spersonality and provide constantattention for years. Thus, caregiversare especially vulnerable tophysical and emotional stress. • Peer support programs can help link caregivers with trained volunteers. Other support programs can offer services geared to caregivers dealing with different stages of AD. Slide 38