EPIDEMIOLOGY & PATHOPHYSIOLOGY

Facts and figures

  • Approximately 5.5 million people in the United States have Alzheimer’s disease (AD).1
    • AD accounts for 60–80% of cases of dementia.1
  • The majority (62%, or 3.3 million) of Americans with AD are women.1
    • Approximately 2.0 million American males have AD.1
  • The large majority (5.3 million) of patients with AD are age 65 years or older.1
    • 1 in 10 older Americans (>65 years) has AD.1
    • An estimated one-third of people aged 85 or older have AD.1
    • Typically, AD develops after age 65 years.1 This late-onset presentation is usually associated with the established memory impairment of AD.
    • More than 200,000 persons younger than 65 years of age are estimated to have younger-onset AD and other dementias.2
      • Early onset AD can develop before age 65 years in patients with a family history of dementia; most patients with early onset AD are diagnosed between 45 and 60 years of age.3,4 Early-onset AD frequently presents with atypical symptoms of AD, including visual dysfunction, apraxia, and/or language dysfunctions, in addition to memory impairment.4
ages-of-people-with-ad

References 1 and 5.

  • Alzheimer’s disease affects people of all races.
    • Non-Hispanic whites comprise the largest racial group of AD patients.1
    • However, the risk of developing AD is higher in African-American and Hispanic populations.1,6,7
    • The proportion of the African-American and Hispanic populations who have AD is higher than in the white population.6,7
  • In 2015, an estimated 64,000 new cases of AD occurred in patients age 65–74 years, 173,000 new cases in patients age 75–84 years, and 243,000 new cases in patients 85 years or older.1
    • The lifetime risk of developing AD is 1:5 for women and 1:10 for men.1
  • As the baby boomer population ages, the number of AD cases is expected to grow rapidly.1
epidemiology-2

Reference 5.

  • Alzheimer’s disease was the 6th leading cause of death in 2015.8
    • The death rate due to Alzheimer’s disease may be underreported for patients who die with other related or unrelated conditions, such as malnutrition or pneumonia, respectively, or due to missed diagnosis.1

Pathophysiology

Alzheimer’s disease is a neurocognitive disorder characterized by the pathologic accumulation of cellular debris—required for the diagnosis of AD—and the progressive loss of neurons, followed by brain atrophy.9

The pathologic hallmarks of AD are extracellular plaques of beta-amyloid protein fragments and intracellular neurofibrillary tangles containing aggregated twisted strands of the tau protein.9

  • Beta-amyloid and tau protein in cerebrospinal fluid are biomarkers to aid in the diagnosis of AD.10
  • Brain imaging with beta-amyloid radiotracers allows the detection of cortical amyloid deposition in the brain, another biomarker of AD.3 Neuroimaging of tau protein is in development.
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  • Normally, an α-secretase cleaves the amyloid-precursor protein (APP) into a non-pathogenic fragments.11 In the AD brain, an alternative pathway is activated in which pathogenic amyloid-beta 42 peptides are generated by the successive cleavage of APP by β-secretase, also known as BACE1, and γ-secretase.11
    • The genes that encode APP and γ-secretase—PSEN1 and PSEN2—are frequently mutated in familial cases of AD.12
    • Aggregation of beta-amyloid induces inflammation in the brain, leading to neuronal dysfunction. 11
    • Additionally, hyperphosphorylation of tau protein disrupts neuronal microtubules and axon structure.11
epidemiology-4

Reference 13.

  • These pathological changes can precede cognitive effects by decades.3
  • Other pathologic changes implicated in neurological damage observed in AD include oxidative stress, neuronal insulin resistance, mitochondrial dysfunction, inflammation, and an imbalance of neurotransmitters.14
  • Neurological diseases can occur alongside AD, contributing to cognitive impairment9:
    • Lewy Body disease, ie, a group of diseases (including Parkinson’s disease) characterized by abnormal accumulation of alpha-synuclein
    • Cerebrovascular disease and vascular brain injury
    • Hippocampal sclerosis and TDP-43 inclusions

References

  1. Alzheimer’s Association. Alzheimer’s Association Report: 2017 Alzheimer’s disease facts and figures. Alzheimer’s Dement. 2017;13:325-373. Full report available at www.alz.org/documents_custom/2017-facts-and-figures.pdf
  2. Alzheimer’s Association. Early-Onset Dementia: A National Challenge, a Future Crisis. Washington, D.C.: Alzheimer’s Association, 2006. Available at www.alz.org/national/documents/report_earlyonset_summary.pdf
  3. Jansen WJ, Ossenkoppele R, Knol DL, et al. Prevalence of cerebral amyloid pathology in persons without dementia: A meta-analysis. JAMA. 2015;313:1924-1938.
  4. Cacace R, Sleegers K, Van Broeckhoven C. Molecular genetics of early-onset Alzheimer’s disease revisited. Alzheimers Dement. 2016;12:733-748.
  5. Hebert LE, Weuve J, Scherr PA, Evans DA. Alzheimer disease in the United States (2010–2050) estimated using the 2010 census. Neurology. 2013;80:1778-1783.
  6. Manly JJ, Mayeux R. Ethnic differences in dementia and Alzheimer’s disease. In: Anderson NB, Bulatao RA, Cohen B, eds. Critical Perspectives on Racial and Ethnic Differences in Health in Late Life. Washington, D.C.: National Academies Press; 2004:95-141. Available at www.nap.edu/catalog/11086.html
  7. Dilworth-Anderson P, Hendrie HC, Manly JJ, Khachaturian AS, Fazio S. Diagnosis and assessment of Alzheimer’s disease in diverse populations. Alzheimers Dement. 2008;4:305-309.
  8. Xu J, Murphy SL, Kochanek KD, Arias E. Mortality in the United States, 2015. NCHS Data Brief. 2016;267:1-8. Available at www.cdc.gov/nchs/data/databriefs/db267.pdf
  9. Hyman BT, Phelps CH, Beach TG, et al. National Institute on Aging-Alzheimer’s Association guidelines for the neuropathic assessment of Alzheimer’s disease. Alzheimers Dement. 2012;8:1-13.
  10. Cummings J, Aisen PS, DuBois B, et al. Drug development in Alzheimer’s disease: the path to 2025. Alzheimer’s Res Ther. 2016;8:39.
  11. Read J, Suphioglu C. Chapter 10: Dropping the BACE: Beta secretase (BACE1) as an Alzheimer’s disease intervention target. In: Kishore U, ed. Neurodegenerative Diseases. InTech; 2013.
  12. Lanoiselée HM, Nicolas G, Wallon D, et al. APP, PSEN1, and PSEN2 mutations in early-onset Alzheimer disease: A genetic screening study of familial and sporadic cases. PLoS Med. 2017;14:e1002270.
  13. Gireud M, Sirisaengtaksin N, Bean AJ. Chapter 21: Molecular Mechanisms of Neurological Disease. ed. Byrne JH, Heidelberger R, Waxham MN. From Molecules to Networks. 3rd ed. Academic Press; 2014:639-661.
  14. Holtzman DM, Morris JC, Goate AM. Alzheimer’s disease: the challenge of the second century. Sci Transl Med. 2011;3:77sr1.

Epidemiology

Challenges

Diagnosis

Biomarkers

Treatments

Additional Reading