Alzheimer’s Disease ; A Disease of Public health concern

Shreejeet Shrestha(Msc. Medical Microbiology, MPH(Mahidol University)

1.Introduction:

Alzheimer’s disease is the most common form of dementia, a serious brain disorder that impacts daily living through memory loss and cognitive changes. Although not all memory loss indicates Alzheimer’s disease, one in ten people over 65 years of age, and over half of those over 85 have Alzheimer’s disease. Currently, 26 million people worldwide have this dementia, and over 15 million Americans will be affected by the year 2050.

In Alzheimer’s disease the symptoms usually develop slowly and gradually worsen over time, progressing from mild forgetfulness to widespread brain impairment. Chemical and structural changes in the brain slowly destroy the ability to create, remember, learn, reason, and relate to others. As critical cells die, drastic personality loss occurs and body systems fail.

2.Global History on Alzhiemer’s(Paul T. et.al.(1998))

1906: Dr. Alois Alzheimer first describes "a peculiar disease"

German physician Alois Alzheimer, a pioneer in linking symptoms to microscopic brain changes, describes the haunting case of Auguste D., a patient who had profound memory loss, unfounded suspicions about her family, and other worsening psychological changes. In her brain at autopsy, he saw dramatic shrinkage and abnormal deposits in and around nerve cells.

1910 Alzheimer's disease namedEmil Kraepelin, a German psychiatrist who worked with Dr. Alzheimer, first names "Alzheimer's Disease" in the eighth edition of his book Psychiatrie.

1970-1979: Modern Research Era

1974

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An act of Congress establishes the National Institute on Aging (NIA) as one of our National Institutes of Health (NIH). The NIA is our primary federal agency supporting Alzheimer's research.

1976 Alzheimer's recognized as most common form of dementiaFounding of National Institute on Aging

1980-1989: Awareness and momentum

1980:Alzeimer's Association founded

In 1979, Jerome H. Stone and representatives from several family support groups met with the National Institute on Aging to explore the value of a national, independent, nonprofit organization to complement and stimulate federal efforts on Alzheimer's disease. That meeting resulted in the 1980 formation of the Alzheimer's Association with Mr. Stone as founding president.

1983 Declaration of National Alzheimer's Disease MonthAwareness of Alzheimer's disease increases, leading Congress to designate November 1983 as the first National Alzheimer's Disease Month.

1984 Beta-amyloid identifiedResearchers George Glenner and Cai'ne Wong report identification of "a novel cerebrovascular amyloid protein," known as beta-amyloid — the chief component of Alzheimer's brain plaques and a prime suspect in triggering nerve cell damage.

1984 Nationwide infrastructure for Alzheimer's research establishedThe NIA begins funding its network of Alzheimer's Disease Centers at flagship medical institutions, establishing a nationwide infrastructure for research, diagnosis and treatment.

1986 1986 Tau protein identifiedResearchers discover that tau protein is a key component of tangles—the second pathological hallmark of Alzheimer's disease and another prime suspect in nerve cell degeneration.

1987 First Alzheimer's drug trialThe Alzheimer's Association assists the NIA and Warner-Lambert Pharmaceutical Company (now Pfizer) in launching and recruiting participants for clinical trials of tacrine, the first drug specifically targeting symptoms of Alzheimer's disease.

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1987 First deterministic Alzheimer's gene identifiedResearchers identify the first gene associated with rare, inherited forms of Alzheimer's disease. This gene on chromosome 21 codes amyloid precursor protein (APP), the parent molecule from which beta-amyloid is formed. Chromosome 21 is also the chromosome of which those with Down syndrome have three copies rather than two. Many individuals with Down syndrome develop Alzheimer's disease, often as young as their 30s and 40s.

1990-1999: Treatments emerge

1991 Federal clinical study consortium launchedThe National Institute on Aging (NIA) established the Alzheimer's Disease Cooperative Study (ADCS), a nationwide medical network to facilitate clinical research and conduct federally funded clinical trials.

1993 First Alzheimer's risk factor gene identifiedResearchers identify APOE-e4, a form of the apolipoprotein-E (APOE) gene on chromosome 19, as the first gene that raises risk for Alzheimer's but does not determine that a person who has it will develop the disease.

1993 First Alzheimer's drug approved by FDAThe Food and Drug Administration (FDA) approves tacrine (Cognex) as the first drug specifically targeting Alzheimer's memory and thinking symptoms. Four additional drugs are approved over the next 10 years.

1995 First transgenic mouse model announcedResearchers announce the first transgenic mouse model that developed Alzheimer-like brain pathology. The mouse was developed by inserting one of the human APP genes linked to a rare, inherited form of Alzheimer's disease.

1999 "Alzheimer's vaccine" successful in miceThe first in a series of reports is published showing that injecting transgenic "Alzheimer" mice with beta-amyloid prevents the animals from developing plaques and other Alzheimer-like brain changes.

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2000-2009: Progress and hope

2003 National Alzheimer's Disease Genetics Study beginsThe Alzheimer's Association partners with the National Institute on Aging to recruit participants for the National Alzheimer's Disease Genetics Study, a federal initiative to collect and bank blood samples from families with several members who developed Alzheimer's disease late in life in order to identify additional Alzheimer's risk genes.

2004 First report on Pittsburgh Compound B (PIB)Researchers at the Alzheimer's Association International Conference on Alzheimer's Disease (AAICAD) share their first report on an imaging agent called Pittsburgh Compound B (PIB), a major potential breakthrough in disease monitoring and early detection. PIB enters the brain through the bloodstream and attaches itself to beta-amyloid deposits, where it can be detected by positron emission tomography (PET). The Alzheimer's Association provided significant support to initiatives to develop PIB and conduct preclinical testing it in animal studies.

2008 International Society to Advance Alzheimer resarch and Treatment formedTo further the work of the global Alzheimer's research community, the Alzheimer's Association creates the International Society to Advance Alzheimer's Research and Treatment (ISTAART), the first and only professional society dedicated to Alzheimer's and Dementia.

2009 International Conference on Alzheimer's Disease beomes an annual event

With accelerating progress intensifying the need for global information exchange, the Alzheimer's Association International Conference on Alzheimer's Disease (AAICAD) becomes an annual event.

2009 Effort to standardize biomarkers beginsThe Alzheimer's Association announces funding of the Alzheimer's Association QC Program for CSF Biomarkers to help overcome variation

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among institutions in measuring potential biomarkers in cerebrospinal fluid (CSF).

2010 Alzheimer's researchers unite to raise awareness and concernDozens of Alzheimer's researchers unite with the Alzheimer's Association for an "Alzheimer's Breakthrough Ride," a 66-day bike relay across America to raise public and congressional awareness of the urgent need for more federal funding to support the search for effective Alzheimer's treatments.

2010 Alzheimer's clinical trial database establishedThe Alzheimer's Association and its partners in the Coalition Against Major Diseases (CAMD) released a first-of-its kind database of 4,000 patients who participated in 11 pharmaceutical industry-sponsored clinical trials of Alzheimer's treatments. The combined data, accessible to any qualified researcher, will offer unprecedented power to understand the course of Alzheimer's.

2010 Alzheimer's Association TrialMatch® launchedThe Association launches TrialMatch, a free, user-friendly tool to help prospective participants identify clinical studies that might be a good fit. Stakeholders have unanimously identified building awareness of studies and increasing enrollment as key strategies to accelerate treatment development.

2010 Alzheimer's advances to sixth-leading cause of US deathsThe Centers for Disease Control and Prevention (CDC) National Center for Health Statistics releases final 2007 data showing that Alzheimer's disease is now our sixth-leading cause of death.

2011 President Obama signs National Alzheimer's Project Act (NAPA) into lawGroundbreaking legislation establishes our first-ever framework for a national strategic plan to address the Alzheimer's crisis and to coordinate our response on multiple fronts, including research, care and support.

2011 New criteria and guidelines for Alzheimer's disease diagnosisThree workgroups convened by the Alzheimer's Association and the National Institute on Aging issue updated criteria and guidelines for diagnosing Alzheimer's disease and propose a research agenda to define a new preclinical stage.

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3.Stages of Alzheimer’s disease

The stages can provide general guidelines for understanding the progression of Alzheimer’s symptoms and planning appropriate care. But each individual with Alzheimer’s progresses differently. Cognitive, physical, and functional phases often overlap, the time in each stage varies widely from patient to patient, and not everyone experiences all Alzheimer’s symptoms.

Stage 1 – Mild/Early (lasts 2-4 yrs) - Frequent recent memory loss, particularly of recent conversations and events. Repeated questions, some problems expressing and understanding language. Mild coordination problems: writing and using objects becomes difficult. Depression and apathy can occur, accompanied by mood swings. Need reminders for daily activities, and may have difficulty driving.

Stage 2 – Moderate/Middle (lasts 2-10 yrs) - Can no longer cover up problems. Pervasive and persistent memory loss, including forgetfulness about personal history and inability to recognize friends and family. Rambling speech, unusual reasoning, and confusion about current events, time, and place. More likely to become lost in familiar settings, experience sleep disturbances, and changes in mood and behavior, which can be aggravated by stress and change. May experience delusions, aggression, and uninhibited behavior. Mobility and coordination is affected by slowness, rigidity, and tremors. Need structure, reminders, and assistance with the activities of daily living.

Stage 3 – Severe/Late (lasts 1-3+ yrs) - Confused about past and present. Loss of ability to remember, communicate, or process information. Generally incapacitated with severe to total loss of verbal skills. Unable to care for self. Falls possible and immobility likely. Problems with swallowing, incontinence, and illness. Extreme problems with mood, behavior, hallucinations, and delirium. In this stage, the person will need round the clock intensive support and care.

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4. Symptoms of Alzhiemer’s Disease

In Alzheimer’s disease, nerve cells in the brain die gradually. This makes it increasingly difficult for brain’s signals to be sent properly. Alzheimer’s disease symptoms may be hard to recognize at first. So symptoms such as mild forgetfulness or an occasional loss of focus are normal signs of aging. But as the disease progresses, Alzheimer’s disease symptoms become more than “normal” changes. They become frightening, incapacitating, and dangerous.

4.1 Symptom of Early Stage

The early stage is often overlooked. Relatives and friends (and sometimes professionals as well) see it as “old age”, just a normal part of ageing process. Because the onset of the disease is gradual, it is difficult to be sure exactly when it begins.

Become forgetful, especially regarding things that just happened May have some difficulty with communication, such as difficulty in finding

words Become lost in familiar places Lose track of the time, including time of day, month, year, season Have difficulty making decisions and handling personal finances Have difficulty carrying out complex household tasks Mood and behaviour:– may become less active and motivated and lose

interest in activities and hobbies – may show mood changes, including depression or anxiety– may react unusually angrily or aggressively on occasion

4.2 Symptom of Middle Stage

As the disease progresses, limitations become clearer and more restricting.

Become very forgetful, especially of recent events and people’s names Have difficulty comprehending time, date, place and events; may become

lost at home as well as in the community Have increasing difficulty with communication (speech and comprehension) Need help with personal care (i.e. toileting, washing, dressing) Unable to successfully prepare food, cook, clean or shop

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Unable to live alone safely without considerable support Behaviour changes may include wandering, repeated questioning, calling

out, clinging, disturbed sleeping, hallucinations (seeing or hearing things which are not there)

May display inappropriate behaviour in the home or in the community (e.g. disinhibition, aggression)

4.3 Symptom of Late Stage

The last stage is one of nearly total dependence and inactivity. Memory disturbances are very serious and the physical side of the disease becomes more obvious.

Usually unaware of time and place Have difficulty understanding what is happen- ing around them Unable to recognize relatives, friends and familiar objects Unable to eat without assistance, may have difficulty in swallowing Increasing need for assisted self-care (bathing and toileting) May have bladder and bowel incontinence Change in mobility, may be unable to walk or be confined to a wheelchair

or bed Behaviour changes, may escalate and include aggression towards carer,

nonverbal agitation (kicking, hitting, screaming or moaning) Unable to find his or her way around in the home

5.Diagnosis for Alzhiemer’s Disease

5.1 Biomarker TestsThe new criteria and guidelines identify two biomarker categories for the diagnosis:

(1) biomarkers showing the level of beta-amyloid accumulation in the brain and(2) biomarkers showing that neurons in the brain are injured or actually degenerating.

Many researchers believe that future treatments to slow or stop theprogression of Alzheimer’s disease and preserve brain function (called“disease-modifying” treatments) will be most effective when administered

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during the preclinical and MCI stages of the disease. Biomarker tests will beessential to identify which individuals are in these early stages and shouldreceive disease-modifying treatment. They also will be critical for monitoringthe effects of treatment. At this time, however, more research is needed tovalidate the accuracy of biomarkers and better understand which biomarkertest or combination of tests is most effective in diagnosing Alzheimer’sdisease. The most effective test or combination of tests may differ depending on the stage of the disease and the type of dementia.

6.Prevalence of Alzheimer’s Disease and Other Dementias

An estimated 5.2 million Americans of all ages have Alzheimer’s disease in 2013. This includes an estimated 5 million people age 65 and older, and approximately 200,000 individuals under age 65 who have younger-onset Alzheimer’s.• One in nine people age 65 and older (11 percent) has Alzheimer’s disease.• About one-third of people age 85 and older (32 percent) have Alzheimer’s disease.• Of those with Alzheimer’s disease, an estimated 4 percent are under age 65, 13 percent are 65 to 74, 44 percent are 75 to 84, and 38 percent are 85 or older.

But in the community, only about half of those who would meet the diagnostic criteria for Alzheimer’s disease and other dementias have received a diagnosis of dementia from a physician. Because Alzheimer’s disease is under-diagnosed, half of the estimated 5.2 million Americans with Alzheimer’s may not know they have it. More women than men have Alzheimer’s disease and other dementias. Almost two-thirds of Americans with Alzheimer’s are women. Out of the 5 million people age 65 and older with Alzheimer’s in the United States, 3.2 million are women and 1.8 million are men. Based on estimates from ADAMS, 16 percent of women age 71 and older have Alzheimer’s disease and other dementias compared with 11 percent of men. The larger proportion of older women who have Alzheimer’s disease and other dementias is primarily explained by the fact that women live longer, on average, than men. Many studies of the age-specific incidence (development of new cases) of Alzheimer’s disease or any dementia have found no significant difference by sex. Thus, women are not more likely than men to develop dementia at any given age.

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7.Incidence and Lifetime Risk of Alzheimer’s Disease

While prevalence is the number of existing cases of a disease in a population at a given time, incidence is the number of new cases of a disease that develop ina given time period. The estimated annual incidence (rate of developing disease in one year) of Alzheimer’s disease appears to increase dramatically with age, fromapproximately 53 new cases per 1,000 people age 65 to 74, to 170 new cases per 1,000 people age 75 to 84, to 231 new cases per 1,000 people age 85 and older (the “oldest-old”). Some studies have found that incidence rates drop off after age 90, but these findings are controversial. One analysis indicates that dementiaincidence may continue to increase and that previous observations of a leveling off of incidence rates among the oldest-old may be due to sparse data for this group. Because of the increasing number of people age 65 and older in the United States, the annual number of new cases of Alzheimer’s and other dementias is projected to double by 2050.• Every 68 seconds, someone in the United States develops Alzheimer’s.• By mid-century, someone in the United States will develop the disease every 33 seconds.Lifetime risk is the probability that someone of a given age develops a condition during their remaining lifespan. Data from the Framingham Study were used to estimate lifetime risks of Alzheimer’s disease and of any dementia. The study found that 65-year-old women without dementia had a 20 percent chance of developing dementia during the remainder of their lives (estimated lifetime risk), compared with a 17 percent chance for men. For Alzheimer’s disease specifically, the estimated lifetime risk at age 65 was nearly one in five (17.2 percent) for women compared with one in 11 (9.1 percent) for men. As previously noted, these differences in lifetime risks between women and men are largely due to women’s longer life expectancy.

8.Alzheimers/Dementia In context of World

Death Rate Per 100,000

Rank Country Rate Rank Country Rate Rank Country Rate

Table:1

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1 Finland 34.9 65 Niger 8.1 129 Belarus 2.5

2 Iceland 25.1 66 Madagascar 8.0 130 Japan 2.5

3 United States 24.8 67 Kenya 8.0 131 Palau 2.5

4 Sweden 21.5 68 Mauritania 8.0 132 Libya 2.4

5 Netherlands 21.4 69 Eritrea 8.0 133 Cambodia 2.4

6 Switzerland 20.0 70 Gambia 7.8 134 Mauritius 2.3

7 Cuba 19.6 71 New Guinea 7.7 135 Sao Tome 2.2

8 Chile 19.6 72 Gabon 7.7 136 Somalia 2.2

9 Andorra 19.4 73 Sierra Leone 7.7 137 Sudan 2.2

10 Spain 18.7 74 Zimbabwe 7.5 138 Afghanistan 2.2

11 Norway 18.6 75 Myanmar 7.4 139 Yemen 2.1

12 Uruguay 17.5 76 Senegal 7.3 140 Lebanon 2.1

13 Denmark 17.4 77 Nepal 7.0 141 Mongolia 2.1

14 United Kingdom 17.1 78 Indonesia 6.8 142 Kazakhstan 2.1

15 France 16.6 79 Botswana 6.6 143 Slovenia 2.1

16 Canada 16.0 80 South Africa 6.6 144 Guyana 2.0

17 Australia 15.3 81 Kiribati 6.5 145 Cook Islands 2.0

18 New Zealand 15.2 82 Portugal 6.4 146 Romania 1.9

19 Belgium 14.6 83 Timor-Leste 6.4 147 Djibouti 1.8

20 Pakistan 14.3 84 Algeria 6.4 148 Egypt 1.8

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21 Bhutan 13.4 85 Bahamas 6.0 149 Greece 1.8

22 Malta 13.0 86 Trinidad/Tob. 6.0 150 Venezuela 1.8

23 South Korea 12.0 87 Cape Verde 5.9 151 Tunisia 1.7

24 Ireland 11.8 88 Argentina 5.9 152 Ukraine 1.7

25 Hungary 11.5 89 Germany 5.9 153 Morocco 1.7

26 Iran 11.4 90 Armenia 5.7 154 Russia 1.6

27 Laos 11.0 91 Haiti 5.1 155 Ecuador 1.6

28 Bangladesh 11.0 92 Croatia 5.1 156 Suriname 1.5

29 St. Kitts 10.8 93 Saint Vincent 5.0 157 Paraguay 1.5

30 Malawi 10.3 94 Latvia 4.6 158 Philippines 1.4

31 Luxembourg 10.3 95 Viet Nam 4.6 159 Turkmenistan 1.4

32 Israel 10.1 96 Austria 4.4 160 Sri Lanka 1.2

33 Guinea-Bissau 9.9 97 Jordan 4.4 161 Guatemala 1.2

34 Rep Of Congo 9.8 98 Tuvalu 4.2 162 Nicaragua 1.1

35 Italy 9.7 99 Moldova 4.2 163 Seychelles 1.1

36 Ethiopia 9.7 100 Dominican Rep 4.1 164 Bulgaria 1.0

37 Cyprus 9.6 101 Marshall Isl. 4.1 165 Nauru 1.0

38 Burundi 9.6 102 Dominica 3.7 166 Belize 0.9

39 Zambia 9.5 103 Serbia/Monten 3.7 167 Bolivia 0.9

40 Costa Rica 9.5 104 Antigua/Bar. 3.5 168 Honduras 0.8

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41 Cameroon 9.5 105 Micronesia 3.5 169 El Salvador 0.8

42 Mozambique 9.5 106 Vanuatu 3.4 170 Jamaica 0.8

43 Chad 9.5 107 Estonia 3.4 171 Bahrain 0.8

44 Central Africa 9.4 108 Samoa 3.4 172 Maldives 0.8

45 Guinea 9.3 109 Albania 3.3 173 Colombia 0.7

46 Congo 9.3 110 Lithuania 3.3 174 San Marino 0.6

47 Syria 9.2 111 Thailand 3.2 175 Yugoslavia 0.5

48 Uganda 9.2 112 China 3.2 176 Qatar 0.5

49 Equ. Guinea 9.2 113 North Korea 3.2 177 Peru 0.5

50 Benin 9.2 114 Tonga 3.1 178 Kyrgyzstan 0.4

51 Nigeria 9.1 115 Solomon Isl. 3.1 179 Brunei 0.4

52 Angola 9.1 116 India 3.1 180 Tajikistan 0.4

53 Liberia 9.1 117 Panama 3.1 181 Kuwait 0.3

54 Cote d Ivoire 9.0 118 Poland 3.0 182 Saudi Arabia 0.2

55 Comoros 9.0 119 Grenada 2.9 183 Oman 0.2

56 Tanzania 9.0 120 Mexico 2.9 184 Azerbaijan 0.2

57 Burkina Faso 8.7 121 Czech Republic 2.9 185 Malaysia 0.2

58 Rwanda 8.6 122 Turkey 2.8 186 Bosnia/Herzeg 0.2

59 Namibia 8.5 123 Saint Lucia 2.7 187 Uzbekistan 0.2

60 Lesotho 8.5 124 Slovakia 2.7 188 Arab Emirates 0.0

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61 Togo 8.4 125 Barbados 2.7 189 Singapore 0.0

62 Swaziland 8.2 126 Iraq 2.6 190 Fiji 0.0

63 Brazil 8.2 127 Niue 2.5 191 Georgia 0.0

64 Mali 8.1 128 Ghana 2.5 192 Monaco 0.0

(Data Source: WHO 2011)

9. Challenges Facing Low and Middle Income Countries‐ ‐In high-income countries, familial efforts to care for those affected by dementia are augmented by pharmaceutical therapies and formal care provided in institutional and home and community-based settings, which are often funded through insurance or other governmental programs. In the majority ofLMIC, however, low awareness of dementia and its impact are reflected in few government policies and programs aimed at addressing the disease. As a result, care for people living with dementia in these regions falls predominantly on families. This dynamic exemplifies unique challenges facing people living .(WHO, Dementia: A Public Health Priority, 2012, p. v. 212 Ibid, p. 13.)

10.Public Health Impact of Deaths from Alzheimer’s DiseaseAs the population of the United States ages, Alzheimer’s is becoming a more common cause of death. While deaths from other major causes have decreased significantly, deaths from Alzheimer’s disease have increased significantly. Between 2000s and 2010, deaths attributed to Alzheimer’s disease increased 68 percent, while those attributed to the number one cause of death, heart disease, decreased 16 percent. The increase in the number and proportion of death certificates listing Alzheimer’s as the underlying cause of death reflects both changes in patterns of reporting deaths on death certificates over time as well as an increase in the actual number of deaths attributable to Alzheimer’s. Another way to describe the impact of Alzheimer’s disease on mortality is through a statistic known as population attributable risk. It represents the proportion of deaths (in a specified amount of time) in a population that may be preventable if a disease were eliminated. The population attributable risk of Alzheimer’s disease on mortality over five years in people age 65 and older is estimated to be between 5 percent and 15 percent. This means that over the next five years, 5

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percent to 15 percent of all deaths in older people can be attributed to Alzheimer’s disease.

11. Cost of CareWHO estimates that total global spending on care for people living with dementia reached $604 billion in 2010.213 Roughly 90% of those resources were spent in high-income countries. Support for people with dementia is funded differently across the world. In high-income countries, roughly 40% of associated costs are borne by the family through informal care, whereas in LMIC, nearly 60% are Health insurance or other social safety net schemes are typically employed in high-income countries to alleviate some of the financial burden associated with caring for loved ones with dementia. Such fiduciary supports are not widely available in most LMIC and the formal social care sector in these areas is ill-equipped, requiring families to assume not only the cost of care, but also the delivery of care. WHO estimates that while 30% of people with dementia live in assisted living facilities or nursing homes in high-income countries, only 11% do in LMIC. ( WHO.Dementia: A Public Health Priority, 2012.)

12.Treatment of Alzheimer’s Disease12.1Pharmacologic TreatmentPharmacologic treatments are treatments in which medication is administered to stop an illness or treat its symptoms. None of the treatments available today forAlzheimer’s disease slows or stops the death and (2013 Alzheimer’s Disease Facts and Figures Overview of Alzheimer’s Disease) malfunction of neurons in the brain that cause Alzheimer’s symptoms and make the disease fatal.However, dozens of drugs and therapies aimed at slowing or stopping brain cell death and malfunction are being studied worldwide. Five drugs have beenapproved by the U.S. Food and Drug Administration that temporarily improve symptoms of Alzheimer’s disease by increasing the amount of chemicals calledneurotransmitters in the brain. The effectiveness of these drugs varies across the population. Despite the lack of disease-modifying therapies, studies have consistently shown that active medical management of Alzheimer’s and other dementias can improve quality of life through all stages of the diseasefor individuals with dementia and their caregivers.Active management includes(1) appropriate use of available treatment options;(2) effective management of coexisting conditions;

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(3) coordination of care among physicians, other health care professionals and lay caregivers;(4) participation in activities and/or adult daycare programs(5) taking part in support groups and supportive services.

12.2Nonpharmacologic TherapyNonpharmacologic therapies are those that employ approaches other than medication, such as cognitive training and behavioral interventions. As withpharmacologic therapies, no nonpharmacologic therapies have been shown to alter the course of Alzheimer’s disease, although some are used with thegoal of maintaining cognitive function or helping the brain compensate for impairments. Other nonpharmacologic therapies are intended to improvequality of life or reduce behavioral symptoms such as depression, apathy, wandering, sleep disturbances, agitation and aggression. A wide range ofnonpharmacologic interventions have been proposed or studied, although few have sufficient evidence supporting their effectiveness. There is some evidence that specific nonpharmacologic therapies may improve or stabilize cognitive function, performance of daily activities, behavior, mood and quality of life.

12.3Treatment In present Situation

12.3.1 FDA-approved drugs

The U.S. Food and Drug Administration (FDA) has approved five medications (listed below) to treat the symptoms of Alzheimer's disease.

Table .2

Drug name Brand name Approved For FDA Approved1. donepezil Aricept All stages 19962. galantamine Razadyne Mild to moderate 20013. memantine Namenda Moderate to

severe2003

4. rivastigmine Exelon Mild to moderate 20005. tacrine Cognex Mild to moderate 1993

13.3.2 How Alzheimer's drugs work

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Neurons are the chief cells destroyed by Alzheimer's disease.

Figure.2 Action on Neuron

In the brain, neurons connect and communicate at synapses, where tiny bursts of chemicals called neurotransmitters carry information from one cell to another. Alzheimer's disrupts this process, and eventually destroys synapses and kills neurons, damaging the brain's communication network.

Current FDA-approved Alzheimer's drugs support this communication process through two different mechanisms:

1) Cholinesterase inhibitors work by slowing down the disease activity that breaks down a key neurotransmitter. Donepezil, galantamine, rivastigmine and tacrine are cholinesterase inhibitors.

2) Memantine,the fifth Alzheimer's drug, is an NMDA (N-methyl-D-aspartate) receptor antagonist, which works by regulating the activity of glutamate, a chemical messenger involved in learning and memory. Memantine protects brain cells against excess glutamate, a chemical messenger released in large amounts by cells damaged by Alzheimer's disease and other neurological disorders. Attachment of glutamate to cell surface "docking sites" called NMDA receptors permits calcium to flow freely into the cell. Over time, this leads to chronic overexposure to calcium, which can speed up cell damage. Memantine prevents this destructive chain of events by partially blocking the NMDA receptors.

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On average, the five approved Alzheimer's drugs are effective for about six to 12 months for about half of the individuals who take them.

Although there is no cure, Alzheimer's medications can temporarily slow the worsening of symptoms and improve quality of life for those with Alzheimer's and their caregivers.

14.Research going on Alzhiemer’s and Recommendations(Ref:A Coming Renaissance In Pharmaceutical Research & Development? John Lechleiter Contributor )

Alzheimer’s disease is a human tragedy – one that tears the mind of an individual and the hearts of families, caregivers, and friends. It is also an economic catastrophe. A new RAND study says that dementia now costs the U.S. up to $215 billion a year in medical care and other costs.

These human and economic costs are set to explode. According to the Alzheimer’s Association, AD today affects more than 5 million Americans, including one out of every eight 65 and older. By 2050, that number is expected to reach 16 million, and AD’s costs in the U.S. could surpass $1 trillion a year, barring medical breakthroughs to slow it down.

It’s estimated that treatments that effectively delay the onset of AD by five years could reduce the cost of care of Alzheimer’s patients in 2050 by $447 billion.

While there are still many theories about what causes Alzheimer’s disease, the most productive line of research to date has been based on the hypothesis that AD starts with the accumulation of amyloid-beta proteins in the brain.

An amyloid “cascade” is believed to initiate when for some reason—genetic, environmental, or some combination—the brain does not eliminate amyloid-beta proteins as well as it once did. As a result, the concentration of amyloid-beta increases and begins to form deposits, known as amyloid plaque, in the brain. This plaque is one of the two hallmarks of AD, going all the way back to Dr. Alzheimer, along with protein tangles found inside nerve cells. We hypothesize that the plaque leads to inflammation that injures brain cells, and ultimately leads to cell death and dementia.

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Most researchers are focusing on blocking the formation of amyloid-beta protein or removing it from the brain, either before or after deposits are formed.

Important new evidence on the key role of amyloid-beta in Alzheimer’s disease came last year from a paper published in Nature. Researchers in Iceland identified a rare genetic mutation that slows the activity of an enzyme called beta secretase, which is required to produce amyloid-beta. Icelanders with the beneficial mutation are more than five times more likely than those without it to reach age 85 without an Alzheimer’s diagnosis.

In addition, results presented last year for our monoclonal antibody solanezumab support the amyloid hypothesis. While the primary endpoints of the two pivotal studies conducted were not met, a secondary analysis of the data demonstrated that a molecule acting specifically on amyloid-beta can slow cognitive decline in patients with mild AD.

A critical problem in treating Alzheimer’s disease is that the plaques associated with AD form long before symptoms appear, and by then treatment is less likely to be effective. In February, the U.S. Food and Drug Administration issued draft guidance designed to assist researchers in developing treatments for patients in the early stages of AD, before noticeable dementia.

Obama administration’s proposed initiative to map the human brain, and its support for increased funding for AD research should be welcomed. Government-supported research plays a critical role in our nation’s R&D infrastructure. But it’s important to note that federal funding for Alzheimer’s research pales in comparison with the investment of the private sector.

The search for solutions to Alzheimer’s disease exemplifies the work of pharmaceutical innovation. Dedicated experts conduct painstaking research over many years, learning from both successes and failures, as piece by piece, answers to the world’s most devastating diseases take shape.

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References:

1. Paul T Francisa et. Al,The cholinergic hypothesis of Alzheimer’s disease: a review of progress,1998

2. National Vital Statistics Reports Volume 61, Number 6 October 10, 2012 Deaths: Preliminary Data for 2011 by Donna L. Hoyert, Ph.D., and Jiaquan Xu, M.D., Division of Vital Statistics

3. Alzheimer’s Disease, Facts and Figures 2012,Overview of Alzheimer’s Disease

4. WHO 2011

5. Alzheimer's disease facts and figures 2013 ,Alzheimer's Association

6. The Alzheimer's Association, 2012, Elsevier Inc

7. WHO, Dementia: A Public Health Priority, 2012, p. v. 212 Ibid, p. 13.

8. WHO, Dementia: A Public Health Priority, 2012. p. v. 212 Ibid, p.42.

9. The World Bank, Global Economic Prospects: Uncertainties and Vulnerabilities, Volume 4,January2012, p.1, WHO, Dementia: A Public Health Priority, 2012, p. 43.

10. Scaling Up Care for Mental, Neurological, and Substance Use Disorders, 2008,

11. A Coming Renaissance In Pharmaceutical Research & Development? John sLechleiter Contributor

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