THE PROGRESSION OF ALZHEIMER’S DISEASE

Alzheimer’s disease (AD) is a slowly progressing, irreversible neurodegenerative brain disease with a long preclinical phase (up to 20 years) and an average clinical duration of 8 to 10 years. The progression of AD is accompanied by changes to the brain that serve as biomarkers of the disease.1,2

The Stages of Alzheimer’s Disease Progression1,3-5

PRECLINICAL AD

Preclinical Alzheimer’s disease (AD) occurs in individuals with evidence of AD pathology who have no clinical symptoms.

MILD COGNITIVE IMPAIRMENT (MCI)

MCI due to AD is evidence of AD pathology along with impairment in 1 or more cognitive domains that does not interfere with daily functioning.

DEMENTIA

Mild AD dementia, moderate AD dementia, and severe AD dementia are when cognitive abilities further decline and cause impairment in functional abilities.

NORMAL COGNITIVE AGING

Alzheimer’s disease symptoms often start subtly. People with early AD (and their families) may mistake the early signs for normal aging and put off going to the doctor.

*This figure is based on a model.

Adapted from Sperling, Copyright 2011, with permission from Elsevier.3 https://www.sciencedirect.com/journal/alzheimers-and-dementia

Normal aging vs Alzheimer’s disease

Alzheimer’s disease symptoms often start subtly. People with early Alzheimer’s disease (and their families) may mistake the early signs for normal aging and put off going to a doctor.1

Disease progression typically spans several stages. These stages include preclinical Alzheimer’s disease, mild cognitive impairment (MCI) due to Alzheimer’s disease, and Alzheimer’s disease dementia varying from mild to severe.1

  • Preclinical Alzheimer’s disease: individuals with evidence of Alzheimer’s disease pathology who have no clinical symptoms6
  • MCI due to Alzheimer’s disease: evidence of Alzheimer’s disease pathology along with impairment in 1 or more cognitive domains that does not interfere with daily functioning6
  • Alzheimer’s disease dementia (mild, moderate, severe): when cognitive abilities further decline and cause impairment in functional abilities6

MCI due to Alzheimer’s disease is a critical stage of the disease continuum1

During this stage, clinicians may be able to detect very early features of Alzheimer’s disease compared to other causes of memory loss or other forms of cognitive impairment. These features can be detected using validated tools such as Mini-Cog, General Practitioner Assessment of Cognition (GPCOG), Memory Impairment Screen (MIS), and Montreal Cognitive Assessment (MoCA).7-9

The time between MCI due to AD and AD dementia is limited

The rate of cognitive decline increases sharply in the years before dementia. Since MCI is the earliest stage of Alzheimer’s disease with observable symptoms, this leaves limited time between diagnosis and dementia—with estimates ranging from 2 to 6 years.1,5,6

Patients with MCI due to AD have been shown to convert to AD dementia at an annual rate of 31%.10

The critical role of biomarker assessment

Biomarkers provide early indications of abnormal pathophysiological changes related to Alzheimer's disease. In the future, it is anticipated that positron emission tomography (PET) imaging or cerebrospinal fluid (CSF) biomarkers will be used to detect the amyloid burden and help support the early detection of Alzheimer’s disease at the MCI due to AD stage.7,11


Should disease-modifying interventions become available in the future, an early and accurate diagnosis of Alzheimer’s disease will be important for initiation of treatment. Biomarker assessment will likely be crucial for this to happen in a timely manner.3,4

What’s Next? Pathophysiology of Alzheimer’s Disease>>

References

  1. Alzheimer’s Association. Alzheimer’s Association Report: 2020 Alzheimer’s disease facts and figures. Alzheimers Dement. 2020;16(3):391-460.
  2. Masters CL, Bateman R, Blennow K, Rowe CC, Sperling RA, Cummings JL. Alzheimer’s disease. Nat Rev Dis Primers. 2015;1:15056. doi:10.1038/nrdp.2015.56.
  3. Sperling RA, Aisen PS, Beckett LA, et al. Toward defining the preclinical stages of Alzheimer’s disease: recommendations from the National Institute on Aging–Alzheimer’s Association workgroups on diagnostic guidelines for Alzheimer’s disease. Alzheimers Dement. 2011;7(3):280-292.
  4. Beason-Held LL, Goh JO, An Y, et al. Changes in brain function occur years before the onset of cognitive impairment. J Neurosci. 2013;33(46):18008-18014.
  5. Wilson RS, Leurgans SE, Boyle PA, Bennett DA. Cognitive decline in prodromal Alzheimer disease and mild cognitive impairment. Arch Neurol. 2011;68(3):351-356.
  6. Morris JC, Blennow K, Froelich L, et al. Harmonized diagnostic criteria for Alzheimer’s disease: recommendations. J Intern Med. 2014;275(3):204-213.
  7. Jack CR Jr, Albert MS, Knopman DS, et al. Introduction to the recommendations from the National Institute on Aging–Alzheimer’s Association workgroups on diagnostic guidelines for Alzheimer’s disease. Alzheimers Dement. 2011;7(3):257-262.
  8. Petersen RC. Mild cognitive impairment. Continuum (Minneap Minn). 2016;22(2):404-418.
  9. Brodaty H, Low L-F, Gibson L, Burns K. What is the best dementia screening instrument for general practitioners to use? Am J Geriatr Psychiatry. 2006;14(5):391-400.
  10. Ottoy J, Niemantsverdriet E, Verhaeghe J, et al. Association of short-term cognitive decline and MCI-to-AD dementia conversion with CSF, MRI, amyloid- and 18F-FDG-PET imaging. Neuroimage Clin. 2019;22:101771. doi:10.1016/j.nicl.2019.101771.
  11. McKhann GM, Knopman DS, Chertkow H, et al. The diagnosis of dementia due to Alzheimer’s disease: recommendations from the National Institute on Aging–Alzheimer’s Association workgroups on diagnostic guidelines for Alzheimer’s disease. Alzheimers Dement. 2011;7(3):263-269.

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