Obsessive-Compulsive Disorder (OCD)

 Understanding obsessive-compulsive disorder (OCD)  

‘When I was four years old, I contracted a terrible case ofImpetigo… The doctor told my mother that I probably got theImpetigo from putting dirty things, such as toys or unwashedFruit, in my mouth, so from that day forward she washedEverything I came in contact with – everything. She washed myPencils and my crayons; she washed my dolls and my dolls’ teaSet (just in case); she washed my food… And most of all sheWashed me. When I came in from playing outside, after I usedThe toilet, after playing with the dog, or just because I wasStanding around and hadn’t been washed for a while… When my hands were dirty, or I thought they were, they had aSpecial feel about them. They felt huge and as though theywere vibrating. I tended to hold them away from myself. Alongwith the sensation in my hands came a gripping feeling in mystomach. My thoughts were, “I can’t feel right until I wash myhands. I must feel right, immediately, or something bad willhappen.” The issue shifted from the dirt on the hands to thefeeling in the stomach, and the vibrating feelings I felt in myhands… My head was saying, “Not dirty – no danger”, but mystomach was still saying, “Danger, danger, do somethingquick!”‘The sky is falling Raeann Dumont ‘He felt compelled to check that “everything was right”, so wouldgo back over almost everything he did. The most serious doubtshe had were about doors, windows and gas taps, which hechecked several times before leaving the house in the morning…and at night. He could not put anything in an envelope or afile, drawer or cabinet without repeatedly checking that he hadwritten exactly the right things.Obsessive-compulsive disorder: the facts Padmal de Silva andStanley Rachman This booklet is an introduction to obsessive-compulsivedisorder (OCD). The symptoms of OCD can be verydistressing and can seriously disrupt normal life. Thisbooklet aims to help people understand it, gives anoutline of the kinds of treatment or help available, andsuggests how people can help themselves.  What is obsessive-compulsive disorder? If you have obsessive-compulsive disorder (OCD), you feel youhave no control over certain thoughts, idea or urges, whichseem to force themselves into your mind, like a stuck record.These thoughts – obsessions – are often frightening or distressing,or seem so unacceptable that you can’t share them with others.Contained within the obsession is an underlying belief thatyou, or other people, may come to harm. However absurd orunrealistic this belief, you can’t dismiss it or reason it away.It creates unbearable anxiety, and makes you feel helpless todo anything except perform the particular ritual which canneutralise the devastating thought. The irresistible urge to carry out such rituals is known as a‘compulsion’. This could be something like repeatedly openingand closing a door, washing hands, repeating a litany, or counting.In other words, exaggerated elements of everyday actions androutines. You may feel compelled to do these actions over andover again, because of an unquenchable fear that you didn’tdo it properly last time, or because the unwanted thoughtsintrude again. The relief from the anxiety is only temporary. OCD is similar to a phobia, which is another anxiety disorder.In both cases, fear brings on symptoms of anxiety and panic,including a racing heart, churning stomach, dizziness, shortnessof breath, sweating and trembling. A phobia also involves anexaggerated fear of something that doesn’t represent a realisticdanger, but other people can usually relate to it, or even shareit. But with OCD the fear is of your own thoughts, and otherpeople may not be able to relate to this or understand them atall. What’s more, someone who has a phobia can avoid thething that triggers their phobia, such as cats or spiders, butwith OCD, these devastating thoughts are unavoidable, andare constantly ready to emerge. (For more information, seeUnderstanding phobias, under Further reading, on p. 14.)  OCD isn’t a psychotic disorder, such as schizophrenia, wherebypeople feel that certain thoughts and ideas come from somewhereoutside themselves (hallucinations). If you have OCD, you knowthat it’s your own thoughts tormenting you. Some people onlyexperience obsessive thoughts, without having any compulsions.Others have compulsions without knowing why they feel theneed to do them. The anxiety caused by experiencing obsessions and compulsionsfeeds back into the problem, creating a vicious circle and makingthe OCD worse. Often, people with OCD are also depressed, andthis may also be partly or wholly due to the experiene of OCD.  What are the signs of OCD? We all worry, occasionally, about whether we’ve left the gas on,or the door locked, and we describe people as being obsessedwith work, football, a girlfriend or boyfriend. Many of us indulgein small, everyday rituals without thinking, such as throwing saltover our shoulder, or not crossing the path of a black cat. Wemay be compulsive in the way we straighten things up, or incleaning more than is strictly necessary. As many as four-fifthsof us may experience minor obsessions or compulsions, suchas these, from time to time. The idea of ‘being obsessed’ issomething that is very much part of everyday language; thedistinction between this and OCD is in its severity. With OCD,the problems are so severe that they interfere with everydaylife. It might mean spending eight to ten hours a day washing,with hands red-raw and bleeding. Or it might mean repeatedlydressing and undressing, or running up and down stairs. You may understand that the way you are behaving is irrational,and may feel ashamed and alone because of it, and unable toask for help. You may not realise how common such problemsare. OCD affects people of all ages. It’s possible that up to threeper cent of the population may experience the symptoms, althoughonly those who are most severely affected usually ask for help.Some research suggests that as many as one per cent of childrenmay have OCD, at any one time. Problems can start as youngas four or five years old, and may continue into adult life. The kind of thoughts and rituals vary from culture to culture,but there are some common examples: Common obsessions• fearing contamination• imagining doing harm• fearing your aggressive urges• intrusive sexual impulses• excessive doubts• ‘forbidden’ thoughts• needing things to be perfect• needing to confess something Common compulsions• washing• repeating actions• checking• touching• counting• ordering or arranging• hoarding or saving• praying  What causes OCD? There are different theories about why OCD develops. The originsmay lie in childhood and early experience. One or both parentsmay have had similar anxiety and shown similar kinds of behaviour,such as obsessional washing, for example (see p. 2). Or it maybe linked to a trauma, such as being sexually abused, possiblycausing an obsessive fear of men and a dread of contaminationby them. The obsessions can be triggered by particular memoriesand experiences. Personality may play a large part in whether and how peoplerespond. It’s suggested that people who are perfectionists bynature may be more prone to obsessions or OCD.  Another theory is that lack of a brain chemical, serotonin, hasa role in OCD, although experts disagree about what that roleis. It’s unclear whether changes in the levels of this chemicalare a cause or effect of the problem, but some medication isbased on adjusting these levels. The way you see the world will influence how you respond tolife. These views may be based on assumptions that are flawedor incorrect, without you even knowing it, because you’ve neverchallenged them. These convictions may have become quiteunshakeable, because your experience of life always seems toreinforce them. To give a very simplified example, you might be brought upby anxious parents to feel your environment is very threatening.This may lead you to believe that unless you wash constantly,dangerous germs may make you very ill. This view could bebased on your parents misunderstanding information from adoctor (see the quote on p. 2). As a result of this, the world mayfeel like a very dangerous place to you, because germs are allaround and can’t be controlled. In this way, your experience oflife may already have made you more prone than average toOCD (and there are likely to be other factors or negativeexperiences contributing to this). If you, or someone you love,then fall very ill, it may reinforce your feelings of vulnerability,making you more anxious. You may begin to be troubled byfrightening thoughts that something bad is going to happento your own children. You may eventually come to feel thatthe only way to keep everybody safe, and to cope with yourintolerable anxiety, is to wash your hands, repeatedly.  What sort of treatment is there? The symptoms of OCD can clearly be very distressing, andperforming endless rituals will have a serious impact on yourlife. While there is no instant cure for OCD, there are a numberof different treatments and coping strategies you could adopt(see p. 10) to help overcome your symptoms. You may want to get professional help, or work out your ownstrategies. There is no right or wrong way to feel or thing to do.Different approaches work for different people. As a first step,you might visit your GP, who could refer you to a psychiatrist orpsychologist. When doctors make a diagnosis of OCD, they use alist of medical criteria. The diagnosis is based on how many ofthese criteria you meet, and it also tells you how severe your problemis, and therefore what sort of treatment might work for you. MedicationSome people find drug treatment helpful for OCD, either aloneor combined with talking treatments (see p. 8). The drugsprescribed most commonly are SSRI antidepressants, such asfluoxetine (trade name, Prozac), fluvoxamine (Faverin), paroxetine(Seroxat) and sertraline (Lustral), which are all licensed for thetreatment of OCD. Fluvoxamine and sertraline may both be givento children under specialist advice. (SSRI antidepressants shouldnot be used to treat depression in children under the age of 18,but this does not apply to these two drugs for treating OCD.)These drugs may have side effects to begin with, includingnausea, headache, sleep disturbance, gastric upsets and increasedanxiety. They may also cause sexual problems. The tricyclicantidepressant clomipramine (Anafranil) is also licensed for thetreatment of obsessional states in adults. The side effects caninclude a dry mouth, blurred vision, constipation, drowsinessand dizziness. Withdrawal symptoms may cause problems. In the past, people may have been given drugs from thebenzodiazepine group, such as diazepam (Valium), to reduceanxiety, but this is now discouraged. They are limited to shortperiods of treatment for those people who are experiencingvery severe anxiety. This is because people may become dependenton them, and because there can be serious problems withwithdrawal. Unfortunately, it’s now clear that many peopleexperience similar problems coming off SSRI antidepressants,especially paroxetine. It’s advisable to withdraw gradually. Youcan find more information about these drugs in Making senseof antidepressants. (See Further reading, on p. 12.) Talking treatmentsSome people have found combining these therapies withmedication especially useful. There are different kinds of suitabletalking treatments, including counselling, psychotherapy andcognitive behaviour therapy. Access to these treatments on theNHS is very variable, but you could also find your own therapistor source of help. (See Useful organisations, on p. 12.) Counsellingprovides support, usually on a once-a-week basis, helping peopledeal with specific problems. Psychotherapy tends to be morefrequent and quite long-term, and focuses on the causes ofdistress, as well as developing coping strategies. Cognitive behaviour therapyCognitive behaviour therapy aims to identify connectionsbetween thoughts, feelings and behaviour, and to help developpractical skills to manage them. There is considerable evidenceto suggest that this therapy is especially effective in dealingwith OCD. The behavioural element (also known as exposuretherapy or desensitization) helps people face fears and reducestheir rituals. You could work with a psychologist, a psychiatrist or a therapistwithin an agreed treatment plan or undertake your ownprogramme. (For more information, see The Mind guide tocognitive behaviour therapy; details of these and other booksand booklets can be found under Further reading, on p. 14.) PsychosurgerySurgery on the brain – psychosurgery, also know asneurosurgery – is sometimes used in severe cases of OCD,when other treatments have been unsuccessful. This treatmentis strictly regulated under the Mental Health Act 1983, andcan’t be given without consent. It’s used very rarely. There ismore information on this in Mind’s Psychosurgery factsheet,available from the website or via MindinfoLine. What help is available? Under the Care Programme Approach (CPA) in England, and itsequivalent in Wales, everyone referred to psychiatric servicesshould be provided with an assessment of their social and healthcare needs, a care plan, a care coordinator and a regular review.  You are entitled to say what your needs are and have a right tohave an advocate, who can listen to you and speak for you, ifyou like. (A member of your family may act as an advocate, oryou can ask about an advocacy service.) The assessment canalso include the needs of carers and relatives. Community Mental Health TeamsThe local Community Mental Health Team (CMHT) can make thisassessment. They provide services in the community through amixed team of social and health care professionals. The teammight include a social worker, (see Community care services,below), a psychiatrist, a psychologist, and a community psychiatricnurse who can help with medication. It may also include acounsellor and community support workers. One of the teammembers will act as care coordinator. He or she should be inregular contact with you. Community care servicesSocial services can make an assessment of your needs forcommunity care services, separately, if required. These involveeverything from day care to housing needs and advice and helpon practical matters, such as accommodation and welfare benefits.Their aim is to provide services in the home or in supportedaccommodation. You might need careworkers, and since manyareas now charge for this, this cost should be included in theneeds assessment. (Whether you have to pay for it yourselfdepends on your financial situation.)  Direct paymentsOnce your community care assessment has confirmed that youneed services, you may be eligible to claim direct payments, whichwill allow you to buy the care you need yourself, rather thansocial services providing it. Local social services or the NationalCentre for Independent Living should be able to provide thisinformation (see Useful organisations, on p. 12).  What can people do for themselves? Treatment of OCD often includes a combination of strategies,including self-help. You may wish to devise your own self-helpprogramme, based on cognitive behaviour therapy techniques.The organisations listed on p. 12 can offer advice and detailsof such programmes. See, also, the self-help books listed underFurther reading, on p. 14. Self-help groupsIt can be useful to share experiences and methods of copingwith others. Self-help groups can provide help, support andencouragement, whether or not you are having professionalhelp. But they can be of particular benefit if you are operatingyour own programme. You could contact your local Mindassociation or social services, who may be able to tell you ifthere is a group local to you. You could also try any of theorganisations listed on p. 12. Relaxation techniquesSome people have found relaxation techniques helpful. Theycan teach you:• how to improve your breathing to lessen tension• physical exercises to do to relax your muscles• action plans to help you progress from coping withnon-stressful situations, to those that you find difficult. For local classes in relaxation techniques, contact your locallibrary or GP. (See, also, Useful organisations, on p. 12, andFurther reading, on p. 14.) Local servicesYou should be able to get information about local mental healthservices from your GP, social services department of your council,local Mind association, Community Mental Health Team, orPatient Advice and Liaison Services (PALS). These include detailsof local projects that provide services to particular communities,such as Black and minority ethnic communities, women, disabledpeople, lesbians and gay men. You may also find details in yourlocal phone book.  What can friends or family do to help? As a friend or family member of someone with OCD, you can helpa lot just by accepting their feelings and knowing that they findit difficult to cope with them. It can be particularly difficult forsomeone experiencing the symptoms of OCD to acknowledgetheir thoughts, and if you give them the impression they arebeing difficult or exaggerating, it can result in greater distressand anxiety. If they are working to a self-help programme, either on theirown or with a therapist of some kind, you could find out howyou can support them with this, or you could go with them totreatment sessions. It can be distressing to be close to someone experiencing OCD.You might find it useful to talk to other people in the samesituation, and to find out more about these complex problems.Try contacting one of the organisations listed on p. 12 or consultingpublications listed under Further reading, on p. 14. Useful organisations MindMind is the leading mental health organisation in England andWales, providing a unique range of services through its localassociations, to enable people with experience of mental distressto have a better quality of life. For more information about anymental health issues, including details of your nearest localMind association, contact the Mind website: www.mind.org.ukor MindinfoLine on 0845 766 0163. British Association for Behavioural and CognitivePsychotherapies (BABCP)The Globe Centre, PO Box 9, Accrington BB5 0XBtel. 01254 875 277, web: www.babcp.org.ukCan provide details of accredited therapists British Association for Counselling and Psychotherapy (BACP)BACP House, 35–37 Albert Street, Rugby CV21 2SGtel. 0870 443 5252, fax: 0870 443 5161email: bacp@bacp.co.uk  web: www.bacp.co.ukSee website or send A5 SAE for details of local practitioners Carers UK20–25 Glasshouse Yard, London EC1A 4JThelpline: 0808 808 7777, tel. 020 7490 8818email: info@ukcarers.org  web: www.carersonline.org.ukInformation and advice on all aspects of caring First Steps to Freedom1 Taylor Close, Kenilworth, Warwickshire CV8 2LWhelpline: 01926 851 608, tel: 01926 864 473email: info@first-steps.org  web: www.first-steps.orgPractical help to those who suffer from obsessive-compulsivedisorders, and to their family and friends International Stress Management Association (ISMA)PO Box 348, Waltham Cross EN8 8ZLtel. 07000 780430, web: www.isma.org.ukA registered charity for the prevention and reduction of stress National Association of Councils for Voluntary Service177 Arundel Street, Sheffield S1 2NUtel. 0114 278 6636, web: www.nacvs.org.ukSupports local voluntary and community sector National Centre for Independent Living (NCIL)250 Kennington Lane, London SE11 5RDtel. 020 7587 1663, email: ncil@ncil.org.ukweb: www.ncil.org.ukProvides information and advice on direct payments National Phobics SocietyZion CRC, 339 Stretford Road, Hulme, Manchester M15 4ZYtel. 0870 770 0456 or 0161 226 5412email: natphob.soc@good.co.uk  web: www.phobics-society.org.ukCounselling and helpline for those suffering from anxiety disorders No Panic93 Brands Farm Way, Randlay, Telford, Shropshire TF3 2JQhelpline: 0808 808 0545, tel. 01952 590 005email: ceo@nopanic.org.uk  web: www.nopanic.org.ukHelpline for people experiencing anxiety disorders OCD ActionAberdeen Centre, 22–24 Highbury Grove, London N5 2EAtel. 020 7226 4000, fax: 020 7288 0828Email: obsessive-action@demon.co.uk web: ocdaction.org.uk

 

Alzheimer’s

Introduction

Alzheimer’s disease is a brain disorder named for German physician Alois Alzheimer, who first described it in 1906. Scientists have learned a great deal about Alzheimer’s disease in the century since Dr. Alzheimer first drew attention to it. Today we know that Alzheimer’s:

• Is a progressive and fatal brain disease. More than 5 million Americans now have Alzheimer’s disease. Alzheimer’s destroys brain cells, causing problems with memory, thinking and behavior severe enough to affect work, lifelong hobbies or social life. Alzheimer’s gets worse over time, and it is fatal. Today it is the seventh-leading cause of death in the United States. For more information, see Symptoms or Stages of Alzheimer’s Disease.

Inside the Brain: An Interactive Tour Learn how the brain works and how Alzheimer’s affects it.

• Is the most common form of dementia, a general term for the loss of memory and other intellectual abilities serious enough to interfere with daily life. Vascular dementia, another common type of dementia, is caused by reduced blood flow to parts of the brain. In mixed dementia, Alzheimer’s and vascular dementia occur together. For more information about other causes of dementia, please see Related Dementias.
• Has no current cure. But treatments for symptoms, combined with the right services and support, can make life better for the millions of Americans living with Alzheimer’s. We’ve learned most of what we know about Alzheimer’s in the last 15 years. There is an accelerating worldwide effort under way to find better ways to treat the disease, delay its onset, or prevent it from developing. Learn more about recent progress in Alzheimer science and research funded by the Alzheimer’s Association in the Research section.

Alzheimer’s and the brain

Just like the rest of our bodies, our brains change as we age. Most of us notice some slowed thinking and occasional problems remembering certain things. However, serious memory loss, confusion and other major changes in the way our minds work are not a normal part of aging. They may be a sign that brain cells are failing.

The brain has 100 billion nerve cells (neurons). Each nerve cell communicates with many others to form networks.
Nerve cell networks have special jobs. Some are involved in thinking, learning and remembering. Others help us see, hear and smell. Still others tell our muscles when to move.

To do their work, brain cells operate like tiny factories. They take in supplies, generate energy, construct equipment and get rid of waste. Cells also process and store information. Keeping everything running requires coordination as well as large amounts of fuel and oxygen.

In Alzheimer’s disease, parts of the cell’s factory stop running well. Scientists are not sure exactly where the trouble starts. But just like a real factory, backups and breakdowns in one system cause problems in other areas. As damage spreads, cells lose their ability to do their jobs well. Eventually, they die.

Learn more about Alzheimer’s: Take the Brain Tour

 

The role of plaques and tangles

Two abnormal structures called plaques and tangles are prime suspects in damaging and killing nerve cells. Plaques and tangles were among the abnormalities that Dr. Alois Alzheimer saw in the brain of Auguste D., although he called them different names.

• Plaques build up between nerve cells. They contain deposits of a protein fragment called beta-amyloid (BAY-tuh AM-uh-loyd). Tangles are twisted fibers of another protein called tau (rhymes with “wow”).
• Tangles form inside dying cells. Though most people develop some plaques and tangles as they age, those with Alzheimer’s tend to develop far more. The plaques and tangles tend to form in a predictable pattern, beginning in areas important in learning and memory and then spreading to other regions.

Scientists are not absolutely sure what role plaques and tangles play in Alzheimer’s disease. Most experts believe they somehow block communication among nerve cells and disrupt activities that cells need to survive.

Early stage and early onset

Early-stage is the early part of Alzheimer’s disease when problems with memory, thinking and concentration may begin to appear in a doctor’s interview or medical tests. Individuals in the early-stage typically need minimal assistance with simple daily routines. At the time of a diagnosis, an individual is not necessarily in the early stage of the disease; he or she may have progressed beyond the early stage. 

The term early-onset refers to Alzheimer’s that occurs in a person under age 65. Early-onset individuals may be employed or have children still living at home. Issues facing families include ensuring financial security, obtaining benefits and helping children cope with the disease. People who have early-onset dementia may be in any stage of dementia – early, middle or late. Experts estimate that some 500,000 people in their 30s, 40s and 50s have Alzheimer’s disease or a related dementia.

History

At a scientific meeting in November 1906, German physician Alois Alzheimer presented the case of “Frau Auguste D.,” a 51-year-old woman brought to see him in 1901 by her family. Auguste had developed problems with memory, unfounded suspicions that her husband was unfaithful, and difficulty speaking and understanding what was said to her. Her symptoms rapidly grew worse, and within a few years she was bedridden. She died in Spring 1906, of overwhelming infections from bedsores and pneumonia.

Dr. Alzheimer had never before seen anyone like Auguste D., and he gained the family’s permission to perform an autopsy. In Auguste’s brain, he saw dramatic shrinkage, especially of the cortex, the outer layer involved in memory, thinking, judgment and speech. Under the microscope, he also saw widespread fatty deposits in small blood vessels, dead and dying brain cells, and abnormal deposits in and around cells.

The condition entered the medical literature in 1907, when Alzheimer published his observations about Auguste D. In 1910, Emil Kraepelin, a psychiatrist noted for his work in naming and classifying brain disorders, proposed that the disease be named after Alzheimer.

Auguste D.

Dr. Alois Alzheimer

More….

from Wiki

Alzheimer’s disease

Alzheimer’s disease (AD), also called Alzheimer disease or simply Alzheimer’s, is the most common cause of dementia, afflicting 24 million people worldwide. Alzhiemer’s in a progressive and terminal disease for which there is currently no cure. In its most common form, it occurs in people over 65 years old (although a less-prevalent early onset form also exists).^[1] It usually begins many years before it is eventually diagnosed. In its early stages, short-term memory loss is the clearest symptom:^[2] this leads to confusion, anger, mood swings, language breakdown, long-term memory loss, and the general ‘withdrawal’ of the sufferer as his or her senses decline. Gradually the sufferer loses minor, and then major bodily functions, until death occurs.^[3] Although the symptoms are common, people commonly experience them in a unique way.^[4] The duration of the disease is commonly cited as being between 5 and 20 years.^[5][6]

Classification

Alzheimer’s is a neurodegenerative disease. Clinical signs of Alzheimer’s disease include progressive cognitive deterioration, declining ability to perform activities of daily living, and neuropsychiatric symptoms or behavioral changes. Plaques which contain misfolded peptides called amyloid beta (Aβ) are formed in the brain many years before the clinical signs of Alzheimer’s are observed. Together, these plaques and neurofibrillary tangles form the pathological hallmarks of the disease. These features can only be discovered at autopsy to confirm the clinical diagnosis. At this time medications can help reduce the symptoms of the disease, but they cannot change the course of the underlying pathology.

The ultimate cause of Alzheimer’s is unknown. Genetic factors are clearly indicated as dominant mutations in three different genes that account for the small number of cases of familial, early-onset AD that have been identified. For the more common form of late onset AD, ApoE is the only clearly established susceptibility gene. All four genes can contain mutations or variants that confer increased risk for AD, but they account for only 30% of the genetic picture of AD. Mutations in any of these four genes lead to the excessive accumulation in the brain of Aβ, the main component of the senile plaques that are prevalent in the brains of AD patients.^[7][8]

[edit] Characteristics

The disease course is typically divided into four stages, with a different pattern of cognitive and functional impairment occurring at each stage.

[edit] Predementia

Careful neuropsychological testing can reveal mild cognitive difficulties up to eight years before a person fullfils clinical criteria of diagnosis.^[9][10][11] It is not yet clear if these difficulties affect daily living activities. Recent studies show impairments in the most complex activities.^[12] The most noticeable deficit for most people is short-term memory loss and the consequent problems to acquire new information, but subtle executive problems or semantic memory impairments can also occur.^[13][14] Apathy can be seen at this stage, which is the most common and most persistent neuropsychiatric symptom through the disease.^[15][16][17] This stage of the disease has also been termed mild cognitive impairment,^[18] but there is still a debate on whether this term corresponds to a different diagnostic entity by itself or just a first step of the disease.^[19]

[edit] Early dementia

In most people with the disease the increasing impairments in learning and memory will lead to diagnosis, while in a small proportion of them language, executive or visuoconstructional difficulties will be more salient.^[20] Nevertheless memory problems do not affect all memory subcapacities equally. Older memories of the patient’s life (episodic memory) and facts he learned (declarative memory); or implicit memory (the memory of the body on how to do things, such as using a knife to eat) are affected to a much lesser degree than the capacities needed to learn new facts or make new memories.^[21][22] On the other hand, language problems are mainly characterized by a shrinking vocabulary and a decreased word fluency which leads to a general impoverishment of oral and written language but the person with the disease is usually capable of communicating ideas adequately.^[23][24][25] While performing fine motor tasks such as writing, drawing or dressing, certain visoconstructional difficulties, or apraxia, may present, which may appear as clumsiness.^[26] As the disease progresses to the middle stage, patients might still be able to live and perform tasks independently for most of the time, but may need assistance or supervision with the most complicated activities.^[20]

[edit] Moderate dementia

In the early stage, people with Alzheimer’s can usually care for themselves. At the moderate stage, progressive deterioration seriously hinders the possibility of independence.^[20] Language difficulties become clearly noticeable: the person makes frequent paraphasias due to difficulties in finding words, and content is poor. Reading and writing are also progressively forgotten.^[23][27] As time passes, complex motor sequences become less coordinated, costing the patient most of his daily-living abilities.^[28] Memory problems worsen, and the person may not recognize close relatives.^[29] Long-term memory, which was previously left intact, is now also impaired.^[30] Patients are usually almost completely unaware of their own deficits, and behavior changes are the norm. Common neuropsychiatric manifestations in this stage are irritability and labile affect, leading to crying or outbursts of unpremeditated aggression and physical violence, even in patients whose life-long behavior has been peaceful. Approximately 30% of the patients also develop illusionary misidentifications and other delusional symptoms.^[15][31] Often urinary incontinence develops.^[32] All these symptoms create stress for relatives and caretakers, increasing the likelihood of moving the patient from home care to other long-term care facilities.^[20][33]

[edit] Advanced

In the last stage of Alzheimer’s disease all human behavior is likely to become entirely automatic. Language is reduced to simple phrases or even single words before being lost altogether.^[23] Nevertheless many patients can receive and return emotional signals long after the loss of verbal language.^[34] Although aggressiveness can still present, extreme apathy and exhaustion are much more common.^[20] Patients will ultimately not be able to perform even the most simple tasks independently. Finally, deterioration of muscle and mobility will develop, leading the patient to become bedridden^[35] and to lose the ability to feed oneself^[36] if death from some external cause (such as infection due to pressure ulcers or pneumonia) does not occur first.^[37][38]

[edit] Etiology

Most cases of Alzheimer’s disease are sporadic, i.e., do not exhibit familial inheritance. Nonetheless, at least 80% of sporadic AD cases most likely involve genetic risk factors. Inheritance of the ε4 allele of the apolipoprotein E (ApoE) gene is regarded as a risk factor for development of up to 50% of late-onset sporadic Alzheimer’s. Genetic experts agree that there are other risk and protective factor genes that influence the development of late onset Alzheimer’s disease. Over 400 genes have been tested for association with late-onset sporadic AD.^[39]

On the other hand, 5 to 10% of AD cases involve a clear familial pattern of inheritance in which the patient has at least two first-degree relatives with a history of AD. These cases often have an early age of onset (usually <60 years). Nearly 200 different mutations in the presenilin-1 or presenilin-2 genes have been documented in over 500 families. Mutations of presenilin 1 (PS1) lead to the most aggressive form of familial Alzheimer’s disease. Over 20 different mutations in the amyloid precursor protein (APP) gene on chromosome 21 can also cause early onset of the disease. The presenilins have been identified as essential components of the proteolytic processing machinery that produces beta amyloid peptides through cleavage of APP. Most mutations in the APP and presenilin genes increase the production of a small protein (peptide) called Abeta42, the main component of senile plaques in brains of AD patients.

[edit] Pathophysiology

Main article: Biochemistry of Alzheimer’s disease

[edit] Neuropathology

MRI images of a normal aged brain (right) and an Alzheimer’s patient’s brain (left). In the Alzheimer brain, atrophy is clearly seen.

At a macroscopic level, AD is characterized by loss of neurons and synapses in the cerebral cortex and certain subcortical regions. This results in gross atrophy of the affected regions, including degeneration in the temporal lobe and parietal lobe, and parts of the frontal cortex and cingulate gyrus.^[40]

Both amyloid plaques and neurofibrillary tangles are clearly visible by microscopy in AD brains.^[41] Plaques are dense, mostly insoluble deposits of protein and cellular material outside and around neurons. Tangles are insoluble twisted fibers that build up inside the nerve cell. Though many older people develop some plaques and tangles, the brains of AD patients have them to a much greater extent and in different brain locations.^[42]

[edit] Biochemical characteristics

Alzheimer’s disease has been identified as a protein misfolding disease, or proteopathy, due to the accumulation of abnormally folded A-beta and tau proteins in the brains of AD patients.^[43] Plaques are made of a peptide called beta-amyloid (also A-beta or Aβ), a protein fragment snipped from a larger protein called amyloid precursor protein (APP). APP is a transmembrane protein; which means that it sticks through the neuron’s membrane; and is believed to help neurons grow, survive and repair themselves after injury.^[44][45] In AD, something causes APP to be divided by enzymes through a mechanism called proteolysis.^[46] One of these fragments is beta-amyloid. Beta-amyloid fragments (amyloid fibrils) outside the cell come together into clumps that deposit outside neurons in dense formations known as senile plaques.^[47][41] AD is also considered a tauopathy due to abnormal aggregation of the tau protein. Healthy neurons have an internal support structure, or cytoskeleton, partly made up of structures called microtubules. These microtubules act like tracks, guiding nutrients and molecules from the body of the cell down to the ends of the axon and back. A special kind of protein, tau, makes the microtubules stable through a process named phosphorylation and is therefore called a microtubule-associated protein.^[48] In AD, tau is changed chemically, becoming hyperphosphorylated. Hyperphosphorylated tau begins to pair with other threads of tau and they become tangled up together inside nerve cell bodies in masses known as neurofibrillary tangles.^[49] When this happens, the microtubules disintegrate, collapsing the neuron’s transport system. This may result first in malfunctions in communication between neurons and later in the death of the cells.^[50]

[edit] Disease mechanism

Three major competing hypotheses exist to explain the cause of the disease. The oldest, on which most currently available drug therapies are based, is known as the “cholinergic hypothesis” and suggests that AD is due to reduced biosynthesis of the neurotransmitter acetylcholine. However, the medications that treat acetylcholine deficiency only affect symptoms of the disease and neither halt nor reverse it.^[51] The cholinergic hypothesis has not maintained widespread support in the face of this evidence, although cholinergic effects have been proposed to initiate large-scale aggregation,^[52] leading to generalized neuroinflammation.^[40]

Research after 2000 includes hypotheses centered on the effects of the misfolded and aggregated proteins, amyloid beta and tau. The two positions differ with one stating that the tau protein abnormalities initiate the disease cascade, while the other states that amyloid beta (Aβ) deposits are the causative factor in the disease.^[53] The tau hypothesis is supported by the long-standing observation that deposition of amyloid plaques does not correlate well with neuron loss,^[54] but a majority of researchers support the alternative hypothesis that Aβ is the primary causative agent.^[53] The amyloid hypothesis is compelling because the gene for the amyloid beta precursor (APP) is located on chromosome 21, and patients with trisomy 21 (Down Syndrome) who thus have an extra gene copy almost universally exhibit AD-like disorders by 40 years of age.^[55][56] The traditional formulation of the amyloid hypothesis points to the cytotoxicity of mature aggregated amyloid fibrils, which are believed to be the toxic form of the protein responsible for disrupting the cell’s calcium ion homeostasis and thus inducing apoptosis.^[57] It should be noted further that ApoE4, the major genetic risk factor for AD, leads to excess amyloid build-up in the brain before AD symptoms arise. Thus, Aβ deposition precedes clinical AD.^[58] Another strong support for the amyloid hypothesis, which looks at Aβ as the common initiating factor for Alzheimer’s disease, is that transgenic mice solely expressing a mutant human APP gene develop fibrillar amyloid plaques.^[59][60][61]

[edit] Diagnosis

Dementia is by definition a clinical condition, and thus can be confidently diagnosed with careful testing. A definitive diagnosis of Alzheimer’s disease as a particular cause of dementia must await microscopic examination of brain tissue; which generally occurs at autopsy and less often with a pre-mortem brain biopsy.^[62] Alzheimer’s disease is usually a clinically diagnosed condition based on the presence of characteristic neurological and neuropsychological features and the absence of alternative diagnoses. In this process, determination of neurological characteristics is made utilizing patient history and clinical observation,^[63] while neuropsychological evaluation includes memory testing and assessment of intellectual functioning.^[64] Medical organizations have created diagnostic criteria to ease and standardize the process for practicing physicians.

[edit] Diagnostic criteria

The diagnostic criteria for Alzheimer of the NINCDS-ADRDA (NINCDS and the ADRDA) are among the most used.^[62] These criteria require that the presence of cognitive impairment and a suspected dementia syndrome be confirmed by neuropsychological testing for a clinical diagnosis of possible or probable AD while they need histopathologic confirmation (microscopic examination of brain tissue) for the definitive diagnosis. They have shown good reliability and validity.^[65] They specify as well eight cognitive domains that may be impaired in AD (i.e., memory, language, perceptual skills, attention, constructive abilities, orientation, problem solving and functional abilities). Similar to the NINCDS-ADRDA Alzheimer’s Criteria are the DSM-IV-TR criteria published by the American Psychiatric Association.^[66][67]

[edit] Diagnostic tools

Neuropsychological screening tests as the Mini mental state examination (MMSE) are widely used to evaluate the cognitive impairments needed for diagnosis, but more comprehensive batteries are necessary for high reliability by this method; especially in the earliest stages of the disease.^[68][69] On the other hand neurological examination in early AD will usually be normal, independently of cognitive impairment; but for many of the other dementing disorders is key for diagnosis. Therefore, neurological examination is crucial in the differential diagnosis of Alzheimer and other diseases.^[64] In addition, interviews with family members are also utilized in the assessment of the disease. Caregivers can supply important information on the daily living abilities, as well as on the decrease over time of the patient’s mental function.^[70] This is especially important since a patient with AD is commonly unaware of his or her own deficits (anosognosia).^[71] Many times families also have difficulties in the detection of initial dementia symptoms and in adequately communicating them to a physician.^[72] Finally supplemental testing provide extra information on some features of the disease or are utilized to rule out other diagnoses. Examples are blood tests, which can identify other causes for dementia different than AD;^[64] some of which may even be reversible;^[73] or psychological tests for depression, as depression can both co-occur with AD or on the contrary be at the origin of the patient’s cognitive impairment.^[74][75]

Increasingly, the functional neuroimaging modalities of SPECT and PET are being used to diagnose Alzheimer’s, as they have shown similar ability to diagnose Alzheimer’s disease as methods involving mental status examination.^[76] Furthermore, the ability of SPECT to differentiate Alzheimer’s disease from other possible causes, in a given patient already known to be suffering from dementia, appears to be superior to attempts to differentiate the cause of dementia cause by mental testing and history.^[77] Another recent objective marker of the disease is the analysis of cerebrospinal fluid for amyloid beta or tau proteins.^[78] Both advances (neuroimaging and cerebrospinal fluid analysis) have led to the proposal of new diagnostic criteria.^[79][64]

[edit] Prevention

Although aging itself cannot be prevented, the senescence of it can be mitigated. The evidence relating certain behaviors, dietary intakes, environmental exposures, and diseases to the likelihood of developing Alzheimer’s varies in quality and its acceptance by the medical community.^[80]

Reducing cardiovascular risk factors, such as hypercholesterolemia, hypertension, diabetes, smoking, lack of physical activity, and high dietary saturated fats are implicated in concomitant reduction in risk for the onset and course of Alzheimer’s disease.^[81]

There are several intellectual or physical activities that may delay the onset or reduce the severity of Alzheimer’s disease. Intellectual stimulation, such as playing chess or completing crossword puzzles,^[82] regular physical exercise,^[83] and regular social interaction^[84] all have a positive effect on the disease.

[edit] Diet

A Mediterranean diet, which includes high consumption of fruit and vegetables, bread, wheat and other cereals, olive oil, olive leaf, fish, and red wine, may affect the risk and course of the disease. The diet is considered to be high in dietary fiber and monounsaturated fat and low in saturated fat.^[85][86] There is some evidence that B-vitamins and folic acid have a positive effect on the prevention and course of the disease.^[87] Recent data from research actually indicates that neither dietary folate nor vitamins B-12 and B-6 have any significant effect on the development of the disease.^[88][89] Another study has ruled out vitamins C and E, individually or in combination, from being correlated with the onset of AD.^[90] In addition, high intake of folate may be associated with cognitive decline in elderly individuals.^[91]

Curcumin in Curry (from the yellow spice Turmeric) may delay disease onset and severity through a possible interaction with metallic ions.^[92][93][94] A large clinical study is underway to determine if the compound has a significant effect in humans.^[95] Other foods or nutrients, such as Omega-3 fatty acids, especially Docosahexaenoic acid (DHA, often found in fish oil),^[96] fresh fruit and vegetables high in the Polyphenol antioxidant (for example, blueberries, apples, grapes, broccoli, and legumes).^[97][98] and the moderate consumption of red wine^[99][100] may all individually or together reduce the risk and development of Alzheimer’s disease.

[edit] Pharmaceuticals

Cholesterol-lowering drugs (statins) can reduce the cardiovascular risk, but have not shown much evidence that they have an effect in preventing or reducing the course of the disease.^[101][102] Other pharmaceutical therapies such as female Hormone replacement therapy is no longer thought to prevent dementia.^[103][104] Long-term usage of non-steroidal anti-inflammatory drugs (NSAIDs), used to reduce joint inflammation and pain, are associated with a reduced likelihood of developing AD, according to some observational studies.^[105]

A 2007 systematic review concluded that there was inconsistent and unconvincing evidence that Ginkgo has any positive effect on dementia or cognitive impairment.^[106] A large, randomized clinical study is now underway, which examines the effect of Ginkgo to prevent dementia. Results are expected in early 2008.^[107]

[edit] Treatment

There is currently no cure for Alzheimer’s disease. Currently available medications offer relatively small symptomatic benefit for some patients and some medications do slow disease progression.^[108]

[edit] Pharmaceutical

There is an observed reduction in activity of the cholinergic neurons in the disease. Acetylcholinesterase inhibitors reduce the rate at which acetylcholine (ACh) is broken down and hence increase the concentration of ACh in the brain (combatting the loss of ACh caused by the death of the cholinergin neurons). AChE-inhibitors seem to modestly moderate symptoms but do not alter the course of the underlying dementing process.^[109] Examples currently marketed include donepezil (Trade name Aricept), galantamine (trade names Reminylin and Nivalin, U.S. trade name Razadyne) and rivastigmine (Exelon). The three products come in an oral form taken once or twice a day. Rivastigmine is also available as a once-daily transdermal patch.^{[110][111][112]}

There is some question as to the effectiveness of cholinesterase inhibitors. Different articles have criticized the design of studies reporting benefit from these drugs, concluding that they have doubtful clinical utility, are costly, and confer many side effects.^{[113][114][115]}

Recent evidence of the involvement of glutamatergic neuronal excitotoxicity in Alzheimer’s disease led to the development and introduction of memantine. Memantine is a novel NMDA receptor antagonist, and has been shown to be moderately clinically efficacious.^{[116][117][108]} Memantine is marketed as Akatinol, Axura, Ebixa and Namenda.

[edit] Psychosocial intervention

Cognitive and behavioral interventions and rehabilitation strategies may be used as an adjunct to pharmacological treatment, especially in the early to moderately advanced stages of disease. Treatment modalities include counseling, psychotherapy (if cognitive functioning is adequate), reminiscent therapy, reality orientation therapy, and behavioral reinforcements as well as cognitive rehabilitation training.^{[118][119][120]}

Modifications to the living environment and lifestyle of the Alzheimer’s patient can improve functional performance and ease caretaker burden. Assessment by an occupational therapist is often indicated. Adherence to simplified routines and labeling of household items to cue the patient can aid with activities of daily living, while placing safety locks on cabinets, doors, and gates and securing hazardous chemicals can prevent accidents and wandering. Changes in routine or environment can trigger or exacerbate agitation, whereas well-lit rooms, adequate rest, and avoidance of excess stimulation all help prevent such episodes.^[121] Appropriate social and visual stimulation can improve function by increasing awareness and orientation. For instance, boldly colored tableware aids those with severe AD, helping people overcome a diminished sensitivity to visual contrast to increase food and beverage intake.^[122]

[edit] Treatments in clinical development

Several potential treatments for Alzheimer’s disease are currently under investigation, including two compounds being studied in phase 3 clinical trials. Tarenflurbil (MPC-7869, formerly R-flubiprofen) is a gamma secretase modulator sometimes called a selective amyloid beta 42 lowering agent. It is believed to reduce the production of the toxic amyloid beta in favor of shorter forms of the peptide.^{[123][124][125]}

Vaccines or immunotherapy for Alzheimer’s, unlike typical vaccines, would be used to treat diagnosed patients rather than for disease prevention. Ongoing efforts are based on the idea that, by training the immune system to recognize and attack beta-amyloid, the immune system might reverse deposition of amyloid and thus stop the disease. Initial results using this approach in animals were promising, and clinical trials of the drug candidate AN-1792 showed results in 20% of patients. In 2002 it was reported that 6% of multi-dosed participants (18 of 300) developed symptoms resembling meningoencephalitis, and the trials were stopped. Participants in the halted trials continued to be followed, and 20% “developed high levels of antibodies to beta-amyloid” and some showed slower progression of the disease, maintaining memory-test levels while placebo-patients worsened. Micro-cererebral hemorrhages during passive immunisation and meningoencephalitis with active immunisation still remain potent threats to this strategy.^{[126][127][128]}

Simvastatin, a statin, stimulates brain vascular endothelial cells to create a beta-amyloid ejector.^[129] The use of this statin may be have a causal relationship to decreased development of the disease.^[130]

Several other pharmaceuticals are under investigation to treat Alzheimer’s disease. A 2006 pilot study showed small but significant improvements in various cognitive rating scales in patients with Alzheimer’s disease after treatment with etanercept, Tumor necrosis factor-alpha receptor fusion protein, which binds to tumor necrosis factor-alpha, and decreases its role in inflammation of nervous tissue.^[131] A further study, administering to a single AD patient via perispinal infusion, showed rapid and significant improvement in Alzheimer’s symptoms.^[132] Laboratory studies with cells and animals continually fuel the pipeline of potential treatments. Some currently approved drugs such as statins and thiazolidinediones have also been under investigation for the treatment and prevention of Alzheimer’s.^[133]

[edit] Epidemiology

Alzheimer’s disease is the most frequent type of dementia in the elderly and affects almost half of all patients with dementia. Correspondingly, advancing age is the primary risk factor for the disease. Among people aged 65, 2–3% show signs of the disease, while 25–50% of people aged 85 have symptoms of Alzheimer’s and an even greater number have some of the pathological hallmarks of the disease without the characteristic symptoms. Every five years after the age of 65, the probability of having the disease doubles.^[134] The share of Alzheimer’s patients over the age of 85 is the fastest growing segment of the Alzheimer’s disease population in the US, although current estimates suggest the 75–84 population has about the same number of patients as the over 85 population.^[135]

Adults with damaged blood vessels in the brain or atrophy in their temporal lobe are more likely to develop Alzheimer’s disease. It is known that blood vessel damage in the brain is more likely to occur in patients with high blood pressure, high cholesterol or diabetes. Prevention of these conditions can lower the risk of developing the disease, as well as heart attack and stroke,^{[136][137][138][139]} Head injury and smoking are also risk factors for AD;^[140][141] while the role of metals in the etiology of the disease is more controversial.^{[142][143][144]}

[edit] Prognosis

As the disease progresses the patient will advance from mild cognitive impairment, when the disease has not yet been diagnosed, to mild and advanced stages of dementia, finally reaching a severe stage of dementia.^[20] It is important to note there is also an important individual variability in the presentation and development of the symptoms; being sometimes difficult to classify the person in one of the described stages. Once Alzheimer’s has been diagnosed, the average life expectancy of patients living with the disease is approximately 7 years, while less than 3% of the patients live more than 14 years.^{[145][146][147][5]}

[edit] Social issues

Alzheimer’s is a major public health challenge since the median age of the industrialized world’s population is increasing gradually.^[148] Indeed, much of the concern about the solvency of governmental social safety nets is founded on estimates of the costs of caring for baby boomers, assuming that they develop Alzheimer’s in the same proportions as earlier generations. For this reason, money spent informing the public of available effective prevention methods may yield disproportionate benefits.

The role of family caregivers has also become more prominent, as care in the familiar surroundings of home may delay onset of some symptoms and delay or eliminate the need for more professional and costly levels of care. Home-based care may entail tremendous economic, emotional, and even psychological costs as well (see elderly care). Family caregivers often give up time from work and forego pay to spend 47 hours per week on average with an affected loved one who frequently cannot be left alone. From a survey of patients with long term care insurance, direct and indirect costs of caring for an Alzheimer’s patient average $77,500 per year.^[149]

[edit] History

Auguste D.

Although the origin of the concept of dementia goes as far back as the ancient Greek and Roman philosophers and physicians;^[150] it was in 1901 when Alois Alzheimer, a German psychiatrist, identified the first case of what became known as Alzheimer’s disease. The patient was a 50-year-old woman called Auguste D. Alois Alzheimer followed her until she died in 1906, when he first reported the case publicly.^{[151][152][153]} In the following five years eleven similar cases were reported in the medical literature; some of them already using the term Alzheimer’s disease.^[150] The official consideration of the disease as a distinctive entity is attributed to Emil Kraepelin, who included “Alzheimer’s disease” or presenile dementia as a subtype of senile dementia in the eighth edition of his Textbook of Psychiatry, published in 1910.^[154]

Accordingly; for most of the twentieth century, the diagnosis of Alzheimer’s disease was reserved for individuals between the ages of 45 and 65 who developed symptoms of dementia. The terminology changed after 1977 when a conference held in that year concluded that the clinical and pathological manifestations of presenile and senile dementia were almost identical, although the authors also added that this did not rule out the possibility of different etiologies. This eventually led to the use of “Alzheimer’s disease” independently of onset age of the disease.^[155][156] The term senile dementia of the Alzheimer type (SDAT) was often used for a time to describe the condition in those over 65, with classical Alzheimer’s disease being used for those younger. Eventually, the term Alzheimer’s disease was formally adopted in medical nomenclature to describe individuals of all ages with a characteristic common symptom pattern, disease course, and neuropathology.^[157]

[edit] Cultural references

Further information: Alzheimer’s in the media

Since Alzheimer’s is such a prevalent disease