Timeline of Alzheimer's disease

Last updated

This is a timeline of Alzheimer's disease , describing especially major discoveries, developments and organizations concerning the disease.

Contents

Year/periodKey developments
Prior to 1890sEarly in History, Solon (638 BC–558 BC) relates alteration in judgment to aging. Plato notes that very old age can have influence on madness. [1]
1890s–1960sPeriod of discovery of Alzheimer's disease, starting virtually with the pioneer work by Alois Alzheimer, until the recognition of the disease in the 1960s. [2] [3]
1970sAlzheimer's disease is recognized as the most common form of dementia. [2]
1980sThe organic constituents of the two characteristic damages of Alzheimer's disease are identified: Beta-amyloid and Tau protein. Many organizations focused on Alzheimer's disease start to be founded across the world. [4]
1990sSeveral genes responsible for the inherited transmission of Alzheimer's disease are identified: PSEN1, PSEN2 and Apolipoprotein E-e4. [4] The first vaccine is used in mice. [2] [3]
2000s–presentAt present, there's no cure for Alzheimer's disease. [5] Incidence is higher in developed countries, which correlates with the proportion of senior citizens. [6]

Full timeline

Year/periodType of eventEventLocation
1892Discovery French pathologist Paul Blocq and Romanian neurologist Gheorghe Marinescu observe senile plaques for the first time. [1] [7]
1898Development Austrian neurologist Emil Redlich relates senile plaques with senile dementia. [1] [8]
1906DiscoveryAt the 37th annual conference of German psychiatrists, physician Alois Alzheimer describes the case of patient Auguste Deter, who had profound memory loss, unfounded suspicions about her family, and other worsening psychological changes. In her brain at autopsy, Alzheimer sees dramatic shrinkage and abnormal deposits in and around nerve cells. [2] [9] Tübingen, Germany
1910DevelopmentGerman psychiatrist Emil Kraepelin, a colleague of Alzheimer, first names "Alzheimer's disease" in the eighth edition of his book Psychiatrie. [2] [10] [11]
1931BackgroundGerman electrical engineer Max Knoll and German physicist Ernst Ruska co-invent the electron microscope, which can magnify up to 1 million times. After World War II the electron microscope becomes common in major research settings, enabling scientists to study brain cells in more detail. [2] [12]
1968DevelopmentResearchers develop the first validated measurement scale for assessing cognitive and functional decline in older adults. [2]
1974OrganizationThe American National Institute on Aging (NIA) is founded. [2] Baltimore, United States
1976ReportAlzheimer's disease is recognized as the most common form of dementia. [2]
1976–1977DevelopmentThree teams, led by Elaine Perry, D.M. Bowen, and P. Davies demonstrate the alteration of central cholinergic systems in Alzheimer's disease. [1] [13]
1978Organization Alzheimer Society of Canada is founded. [14] [15] Toronto, Canada
1980Organization American Alzheimer's Association is founded. [16] Chicago, United States
1980OrganizationAlzheimer's Association Japan is founded. It is involved in research and provides support for those affected by Alzheimer's. [17] Kyoto, Japan
1982OrganizationAlzheimer’s Australia is founded. It administers leading edge national dementia programs and services and is funded by the Commonwealth. [14] [18] [19] North Ryde, Australia
1983Campaign American president Ronald Reagan designates November as National Alzheimer’s Disease Awareness Month with the purpose of raising awareness for Alzheimer’s disease. [20] United States
1984DiscoveryResearchers George Glenner and Caine Wong identify protein known as amyloid beta, the main component of the amyloid plaques found in the brains of Alzheimer patients. [1] [2]
1984OrganizationAlzheimer Nederland is founded. [14] [21] [22] [23] Amersfoort, Netherlands
1984Organization Alzheimer's Disease International is founded. [24] London, United Kingdom
1985OrganizationAssociation France Alzheimer is founded. It provides financial help for research. [25] [26] [27] Paris, France
1985OrganizationAlzheimer's South Africa is founded. It provides funds for research. [14] [28] [29] Bryanston, South Africa
1986Discovery Belgian physician Jean-Pierre Brion identifies Tau protein as a key component of neurofibrillary tangles, the second pathological hallmark of Alzheimer's disease and another prime suspect in nerve cell degeneration. [2] [4]
1987Discovery Amyloid precursor protein (APP) is discovered. It is the first gene with mutations found to cause an inherited form of Alzheimer's disease. [30]
1988OrganizationFederazione Alzheimer Italia is founded. It delivers free training courses for carers, among other activities. [14] [31] [32] Milan, Italy
1988OrganizationAssociation Alzheimer Suisse is founded. It provides information and help for those affected by Alzheimer's. [14] [33] [34] Yverdon-les-Bains, Switzerland
1988OrganizationAlzheimer's Association of Israel is founded. In 2008, the association launched “In the Armchair with Picasso” art-kit for therapeutic use on those affected with Alzheimer's. This project has brought attention from geriatric professionals around the world. [14] [35] [36] Ramat Gan, Israel
1989OrganizationDeutsche Alzheimer Gesellschaft is founded. It provides funding for research. [14] [37] [38] Berlin, Germany
1989OrganizationAsociación de Lucha contra el Mal de Alzheimer is founded. It elaborates projects and holds its own scientific committee. [14] [39] [40] [41] Buenos Aires, Argentina
1990OrganizationConfederación Española de Familiares de Enfermos de Alzheimer is founded. It represents thirteen federations and six associations within the country. [14] [42] [43] Pamplona, Spain
1992OrganizationAlzheimer's & Related Disorders Society of India is founded. It is the first Afro-Asian organization to receive full membership with Alzheimer Disease International and has an official relationship with the WHO. [14] [44] [45] Kunnamkulam, India
1992Discovery Presenilin-1 (PS-1) is identified. It is the second gene with mutations found to cause inherited Alzheimer's disease. Variations in this gene are the most common cause of inherited Alzheimer's. [30]
1993Discovery Presenilin-2 (PS-2) is discovered. It is the third gene with mutations found to cause inherited Alzheimer's disease. [30] [46]
1993Discovery Apolipoprotein E-e4 (APOE4) is discovered. It is the first gene variation found to increase risk of Alzheimer's disease and remains the risk gene with the greatest known impact. [30] [47]
1993DevelopmentThe United States Food and Drug Administration (FDA) approves tacrine (Cognex) as the first drug specifically targeting Alzheimer's disease memory and thinking symptoms. [2] United States
1994Alzheimer Disease International launches the first World Alzheimer's Day on September 21. [2]
1995DevelopmentResearchers announce the first transgenic mouse model that developed Alzheimer-like brain pathology, by inserting one of the human APP genes linked to a rare, inherited form of Alzheimer's disease. [2] [48]
1996Development Donepezil is approved for use in all stages of Alzheimer's disease. [49] United States
1999DevelopmentFirst report announcing that injection of transgenic "Alzheimer" mice with beta-amyloid prevents the animals from developing plaques and other Alzheimer's disease-like brain changes. [2]
2001Development Galantamine is approved for use in mild to moderate stages of Alzheimer's disease. [49] United States
2002OrganizationThe Federación Mexicana de Alzheimer is founded. It holds its own scientific committee. [14] [50] [51] Monterrey, Mexico
2003Development Memantine is approved for use in moderate to severe stages of Alzheimer's disease. [49] United States
2003StudyThe National Alzheimer's Disease Genetics Study begins. Blood samples are collected from families with several members who developed Alzheimer's late in life to identify additional Alzheimer's risk genes. [11] United States
2006Development Rivastigmine is approved for use in all stages of Alzheimer's disease. [49] United States
2008OrganizationThe International Society to Advance Alzheimer Research and Treatment is founded. [2] [52]
2009OrganizationThe International Conference on Alzheimer's disease becomes an annual event. [2]
2010DevelopmentA database is launched containing information of more than 4000 patients with Alzheimer's disease who participated in 11 pharmaceutical industry-sponsored clinical trials of Alzheimer's treatments. [11] [53] United States
2012OrganizationMultinational research consortium Dominantly Inherited Alzheimer Network (DIAN), launches the first major clinical trial testing pharmacotherapy to prevent the onset of Alzheimer’s disease symptoms in people who inherited an autosomal dominant mutation putting them at high risk for the disease. [2]
2013DiscoveryInternational Genomics of Alzheimer’s Project (IGAP) researchers identify 20 genetic variations associated with increased risk of Alzheimer’s disease. [2]
2013CampaignThe G8 Dementia Summit launches an international effort to fight Alzheimer’s disease and find a cure by 2025. [54] United Kingdom
2014DiscoveryResearchers at Rush University come to the conclusion that rates of death caused by Alzheimer’s disease are found to be much higher than reported on death certificates. The study is performed on organs donated from 2,566 persons aged 65 years and older without dementia at baseline. [2] [55] United States
2016ReportAccording to Alzheimer Disease International, nearly 44 million people have Alzheimer’s disease or a related dementia worldwide. [56]

See also

Related Research Articles

Acute disseminated encephalomyelitis autoimmune disease marked by sudden, widespread inflammation of the brain and spinal cord

Acute disseminated encephalomyelitis (ADEM), or acute demyelinating encephalomyelitis, is a rare autoimmune disease marked by a sudden, widespread attack of inflammation in the brain and spinal cord. As well as causing the brain and spinal cord to become inflamed, ADEM also attacks the nerves of the central nervous system and damages their myelin insulation, which, as a result, destroys the white matter. It is often triggered by a viral infection or specific non-routine vaccinations.

Parkinsonism symptoms that resemble Parkinsons disease

Parkinsonism is a clinical syndrome characterized by tremor, bradykinesia, rigidity, and postural instability. It is found in Parkinson's disease (PD), after which it is named, dementia with Lewy bodies (DLB), Parkinson's disease dementia (PDD), and many other conditions. A wide range of causes may lead to this set of symptoms, including neurodegenerative conditions, drugs, toxins, metabolic diseases, and neurological conditions other than PD.

Erotomania is listed in the DSM-5 as a subtype of a delusional disorder. It is a relatively uncommon paranoid condition that is characterized by an individual's delusions of another person being infatuated with them. This disorder is most often seen in female patients who are shy, dependent and sexually inexperienced. The object of the delusion is typically a male who is unattainable due to high social or financial status, marriage or disinterest. The object of obsession may also be imaginary, deceased or someone the patient has never met. Delusions of reference are common, as the erotomanic individual often perceives that they are being sent messages from the secret admirer through innocuous events such as seeing license plates from specific states, but has no research development proof. Commonly, the onset of erotomania is sudden, and the course is chronic.

Sex differences in medicine include sex-specific diseases or conditions which occur only in people of one sex ; sex-related diseases, which are diseases that are more common to one sex ; and diseases which occur at similar rates in males and females but manifest differently according to sex. Sex differences in medicine should not be confused with gender differences. The Institute of Medicine recognizes sex differences as biological at the chromosomal level, whereas gender differences are based on self-representation and other factors including biology, environment and experience. Sex differences in medicine should also not be confused with sexually transmitted diseases, which are diseases that have a significant probability of transmission through sexual contact.

Lewy body dementia is an umbrella term that encompasses two similar dementias, both of which are characterized by abnormal deposits of the protein alpha-synuclein in the brain:

Transmissible spongiform encephalopathies (TSEs) are a group of progressive, invariably fatal, conditions that are associated with prions and affect the brain (encephalopathies) and nervous system of many animals, including humans, cattle, and sheep. According to the most widespread hypothesis, they are transmitted by prions, though some other data suggest an involvement of a Spiroplasma infection. Mental and physical abilities deteriorate and many tiny holes appear in the cortex causing it to appear like a sponge when brain tissue obtained at autopsy is examined under a microscope. The disorders cause impairment of brain function, including memory changes, personality changes and problems with movement that worsen chronically.

Resveratrol Chemical compound

Resveratrol (3,5,4′-trihydroxy-trans-stilbene) is a stilbenoid, a type of natural phenol, and a phytoalexin produced by several plants in response to injury or when the plant is under attack by pathogens, such as bacteria or fungi. Sources of resveratrol in food include the skin of grapes, blueberries, raspberries, mulberries, and peanuts.

Demyelinating disease Any neurological disease in which the myelin sheath of neurons is damaged

A demyelinating disease is any disease of the nervous system in which the myelin sheath of neurons is damaged. This damage impairs the conduction of signals in the affected nerves. In turn, the reduction in conduction ability causes deficiency in sensation, movement, cognition, or other functions depending on which nerves are involved.

Locus coeruleus Stress & Panic Reponse Center

The locus coeruleus is a nucleus in the pons of the brainstem involved with physiological responses to stress and panic. It is a part of the reticular activating system.

Alexander disease Rare genetic disorder of the white matter of the brain

Alexander disease is a very rare autosomal dominant leukodystrophy, which are neurological conditions caused by anomalies in the myelin which protects nerve fibers in the brain. The most common type is the infantile form that usually begins during the first 2 years of life. Symptoms include mental and physical developmental delays, followed by the loss of developmental milestones, an abnormal increase in head size and seizures. The juvenile form of Alexander disease has an onset between the ages of 2 and 13 years. These children may have excessive vomiting, difficulty swallowing and speaking, poor coordination, and loss of motor control. Adult-onset forms of Alexander disease are less common. The symptoms sometimes mimic those of Parkinson’s disease or multiple sclerosis, or may present primarily as a psychiatric disorder.

Neuromyelitis optica (NMO) is a heterogeneous condition consisting of the inflammation and demyelination of the optic nerve and the spinal cord (myelitis). It can be monophasic or recurrent. Currently at least three different kinds are proposed based on the presence of autoantibodies thought to produce the disease: anti-AQP4, anti-MOG and anti-NF. All the cases are considered autoimmune diseases.

Progressive supranuclear palsy (PSP) is a degenerative disease involving the gradual deterioration and death of specific volumes of the brain. The condition leads to symptoms including loss of balance, slowing of movement, difficulty moving the eyes, and dementia. PSP may be mistaken for other neurodegenerative diseases such as Parkinson's and Alzheimer's. The cause of the condition is uncertain, but involves accumulation of tau protein within the brain. Medications such as levodopa and amantadine may be useful in some cases.

The Mini-Mental State Examination (MMSE) or Folstein test is a 30-point questionnaire that is used extensively in clinical and research settings to measure cognitive impairment. It is commonly used in medicine and allied health to screen for dementia. It is also used to estimate the severity and progression of cognitive impairment and to follow the course of cognitive changes in an individual over time; thus making it an effective way to document an individual's response to treatment. The MMSE's purpose has been not, on its own, to provide a diagnosis for any particular nosological entity.

A gamma wave is a pattern of neural oscillation in humans with a frequency between 25 and 140 Hz, the 40-Hz point being of particular interest. Gamma rhythms are correlated with large scale brain network activity and cognitive phenomena such as working memory, attention, and perceptual grouping, and can be increased in amplitude via meditation or neurostimulation. Altered gamma activity has been observed in many mood and cognitive disorders such as Alzheimer's disease, epilepsy, and schizophrenia.

Primary progressive aphasia progressive language and speech disorder

Primary progressive aphasia (PPA) is a type of neurological syndrome in which language capabilities slowly and progressively become impaired. As with other types of aphasia, the symptoms that accompany PPA depend on what parts of the left hemisphere are significantly damaged. However, unlike most other aphasias, PPA results from continuous deterioration in brain tissue, which leads to early symptoms being far less detrimental than later symptoms. Those with PPA slowly lose the ability to speak, write, read, and generally comprehend language. Eventually, almost every patient becomes mute and completely loses the ability to understand both written and spoken language. Although it was first described as solely impairment of language capabilities while other mental functions remain intact, it is now recognized that many, if not most of those afflicted suffer from impairment of memory, short term memory formation and loss of executive functions. It was first described as a distinct syndrome by M.‑Marsel Mesulam in 1982. Primary progressive aphasias have a clinical and pathological overlap with the frontotemporal lobar degeneration (FTLD) spectrum of disorders and Alzheimer's disease. However, PPA is not considered synonymous to Alzheimer's disease due to the fact that, unlike those affected by Alzheimer's disease, those with PPA are generally able to maintain the ability to care for themselves, remain employed, and pursue interests and hobbies. Moreover, in diseases such as Alzheimer's disease, Pick's disease, and Creutzfeldt-Jakob disease, progressive deterioration of comprehension and production of language is just one of the many possible types of mental deterioration, such as the progressive decline of memory, motor skills, reasoning, awareness, and visuospatial skills.

Neurodegeneration Central nervous system disease

Neurodegeneration is the progressive loss of structure or function of neurons, including death of neurons. Many neurodegenerative diseases – including amyotrophic lateral sclerosis, Parkinson's disease, Alzheimer's disease, fatal familial insomnia, and Huntington's disease – occur as a result of neurodegenerative processes. Such diseases are incurable, resulting in progressive degeneration and/or death of neurons. As research progresses, many similarities appear that relate these diseases to one another on a sub-cellular level. Discovering these similarities offers hope for therapeutic advances that could ameliorate many diseases simultaneously. There are many parallels between different neurodegenerative disorders including atypical protein assemblies as well as induced cell death. Neurodegeneration can be found in many different levels of neuronal circuitry ranging from molecular to systemic.

<i>beta</i>-Methylamino-<small>L</small>-alanine

β-Methylamino-l-alanine, or BMAA, is a non-proteinogenic amino acid produced by cyanobacteria. BMAA is a neurotoxin and its potential role in various neurodegenerative disorders is the subject of scientific research.

Genetic heterogeneity occurs through the production of single or similar phenotypes through different genetic mechanisms. There are two types of genetic heterogeneity: allelic heterogeneity, which occurs when a similar phenotype is produced by different alleles within the same gene; and locus heterogeneity, which occurs when a similar phenotype is produced by mutations at different loci.

Tumefactive multiple sclerosis

Tumefactive multiple sclerosis is a condition in which the central nervous system of a person has multiple demyelinating lesions with atypical characteristics for those of standard multiple sclerosis (MS). It is called tumefactive as the lesions are "tumor-like" and they mimic tumors clinically, radiologically and sometimes pathologically.

Hydrogen water is water with dissolved hydrogen gas (H2) similar to carbonated water in which the dissolved gas is carbon dioxide. It is tasteless since H2 is an odorless gas. There is limited scientific evidence that hydrogen water has any health benefits in humans, although its proponents make claims it provides such benefits as functioning as an antioxidant, reducing inflammation, reducing risk of metabolic syndrome, providing neuroprotection for various diseases, and reducing side effects associated with cancer radiation treatment.

References

  1. 1 2 3 4 5 "Histoire de la maladie d'Alzheimer" (PDF). Retrieved 11 August 2016.
  2. 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 "Major Milestones in Alzheimer's and Brain Research" . Retrieved 9 August 2016.
  3. 1 2 "L'histoire de la Maladie d'Alzheimer" . Retrieved 11 August 2016.
  4. 1 2 3 "Historique de la maladie Alzheimer" . Retrieved 11 August 2016.
  5. "Treatments for Alzheimer's disease" . Retrieved 11 August 2016.
  6. Chengxuan Qiu, Miia Kivipelto, Eva von Strauss (2009). "Epidemiology of Alzheimer's disease: occurrence, determinants, and strategies toward intervention". Dialogues Clin Neurosci. 11: 111–28. PMC   3181909 . PMID   19585947.CS1 maint: multiple names: authors list (link)
  7. Buda O, Arsene D, Ceausu M, Dermengiu D, Curca GC (January 2009). "Georges Marinesco and the early research in neuropathology". Neurology. 72: 88–91. doi:10.1212/01.wnl.0000338626.93425.74. PMID   19122036.CS1 maint: multiple names: authors list (link)
  8. Castellani, Rudy. Molecular Pathology of Alzheimer's Disease. p. 9.
  9. "History Module: Dr. Alois Alzheimer's First Cases" . Retrieved 11 August 2016.
  10. Hanns Hippius, Gabriele Neundörfer (2003). "The discovery of Alzheimer's disease". Dialogues Clin Neurosci. 5: 101–8. PMC   3181715 . PMID   22034141.
  11. 1 2 3 "Proposed Alzheimer's criteria call for early physician intervention" . Retrieved 12 August 2016.
  12. Tim Palucka. "Overview of Electron Microscopy" . Retrieved 11 August 2016.
  13. P. Francis, A. Palmer, M. Snape, G. Wilcock (February 1999). "The cholinergic hypothesis of Alzheimer's disease, a review of progress". J. Neurol. Neurosurg. Psychiatry. 66: 137–47. doi:10.1136/jnnp.66.2.137. PMC   1736202 . PMID   10071091.CS1 maint: multiple names: authors list (link)
  14. 1 2 3 4 5 6 7 8 9 10 11 12 "Alzheimer associations" . Retrieved 11 August 2016.
  15. "Alzheimer Society of Canada" . Retrieved 10 August 2016.
  16. "Alzheimer's Association" . Retrieved 10 August 2016.
  17. "Japan steps up search for Alzheimer's cure" . Retrieved 13 August 2016.
  18. "Alzheimer's Australia" . Retrieved 21 November 2016.
  19. "About Alzheimer's Australia" . Retrieved 13 August 2016.
  20. "National Alzheimer's Disease Awareness Month" . Retrieved 11 August 2016.
  21. "Alzheimer Nederland" . Retrieved 21 November 2016.
  22. "Alzheimer Nederland" . Retrieved 10 August 2016.
  23. "Alzheimer's Society/Alzheimer Nederland knowledge exchange fellowships" . Retrieved 13 August 2016.
  24. "Alzheimer's Disease International" . Retrieved 10 August 2016.
  25. "France Alzheimer" . Retrieved 21 November 2016.
  26. Ando K, Laborde Q, Lazar A, Godefroy D, Youssef I, Amar M, Pooler A, Potier MC, Delatour B, Duyckaerts C (2014). "Inside Alzheimer brain with CLARITY: senile plaques, neurofibrillary tangles and axons in 3-D". Acta Neuropathol. 128: 457–9. doi:10.1007/s00401-014-1322-y. PMC   4131133 . PMID   25069432.CS1 maint: multiple names: authors list (link)
  27. "Association France Alzheimer" . Retrieved 10 August 2016.
  28. "Alzheimer's South Africa" . Retrieved 11 August 2016.
  29. "Dementia: SA's hidden disease" . Retrieved 13 August 2016.
  30. 1 2 3 4 "The Search for Alzheimer's Causes and Risk Factors" . Retrieved 9 August 2016.
  31. "Alzheimer Europe" (PDF). Retrieved 13 August 2016.
  32. "Federazione Alzheimer Italia" . Retrieved 10 August 2016.
  33. "Dégénérescence. La véritable bataille contre l'alzheimer commence" . Retrieved 13 August 2016.
  34. "Association Alzheimer Suisse" . Retrieved 11 August 2016.
  35. "Virtual museum tours perk up people with dementia". 13 August 2016.
  36. "Alzheimer's Association of Israel" . Retrieved 10 August 2016.
  37. "Deutsche Alzheimer Gesellschaft" . Retrieved 21 November 2016.
  38. "DAlzG offer research funding opportunity" . Retrieved 13 August 2016.
  39. "Las demencias, en la agenda política mundial" . Retrieved 13 August 2016.
  40. "Asociación de Lucha contra el Mal de Alzheimer" . Retrieved 13 August 2016.
  41. "Asociación de Lucha contra el Mal de Alzheimer" . Retrieved 10 August 2016.
  42. "Alzheimer España" . Retrieved 13 August 2016.
  43. "Confederación Española de Familiares de Enfermos de Alzheimer" . Retrieved 10 August 2016.
  44. "Alzheimer's & Related Disorders Society of India" . Retrieved 13 August 2016.
  45. "Alzheimer's & Related Disorders Society of India" . Retrieved 10 August 2016.
  46. "ALZHEIMER'S DRUG APPROVED BY F.D.A." Retrieved 11 August 2016.
  47. Mengying Liu, Chen Bian, Jiqiang Zhang, Feng Wen (2014). "Apolipoprotein E gene polymorphism and Alzheimer's disease in Chinese population: a meta-analysis". Sci Rep. 4: 4383. doi:10.1038/srep04383. PMC   3955907 . PMID   24632849.CS1 maint: multiple names: authors list (link)
  48. "Mouse Models of Alzheimer's Disease: A Quest for Plaques". ILAR Journal. 43: 89–99. doi: 10.1093/ilar.43.2.89 .
  49. 1 2 3 4 "Current Alzheimer's Treatments" . Retrieved 11 August 2016.
  50. "Alzheimer Mexico" . Retrieved 13 August 2016.
  51. "Federación Mexicana de Alzheimer" . Retrieved 10 August 2016.
  52. Adejare, Adeboye. Drug Discovery Approaches for the Treatment of Neurodegenerative Disorders . Retrieved 21 November 2016.
  53. Deborah Brauser. "New Database of Alzheimer's Trials Available to Researchers, Clinicians" . Retrieved 12 August 2016.
  54. "History of Alzheimer's: Major Milestones" . Retrieved 11 August 2016.
  55. James BD, Leurgans SE, Hebert LE, Scherr PA, Yaffe K, Bennett DA. "Contribution of Alzheimer disease to mortality in the United States". Neurology. 82: 1045–50. doi:10.1212/WNL.0000000000000240. PMC   3962992 . PMID   24598707.CS1 maint: multiple names: authors list (link)
  56. "2016 Alzheimer's Statistics" . Retrieved 11 August 2016.